BACKGROUND Epilepsy impacts millions of people,with many not responding to existing treatments.Some evidence links neuroinflammatory processes to epilepsy.Statins exhibit anti-inflammatory and neuroprotective properti...BACKGROUND Epilepsy impacts millions of people,with many not responding to existing treatments.Some evidence links neuroinflammatory processes to epilepsy.Statins exhibit anti-inflammatory and neuroprotective properties,potentially offering antiepileptic effects.AIM To evaluate the anticonvulsant effects of rosuvastatin in animal models of epilepsy.METHODS Ninety-six albino mice were divided into 16 groups.In the maximal electroshock seizure(MES)model,eight groups received intraperitoneal vehicle,carbama-zepine,rosuvastatin,or a combination.Outcomes measured included seizure protection[tonic hind limb extension(THLE)],duration of THLE,seizure duration,and mortality.In the pentylenetetrazol(PTZ)model,eight groups were pretreated with vehicle,valproate,rosuvastatin,or a combination,with outcomes measured as seizure latency,seizure duration,and mortality.RESULTS In the MES model,rosuvastatin exhibited protection against THLE in a small percentage of mice.Rosuvastatin shortens the duration of THLE in a dose-dependent manner.However,none of these were statistically significant com-pared to the control group.The combination of rosuvastatin 10 mg/kg with carbamazepine 4 mg/kg resulted in a significant reduction in seizure duration compared to the control group,better than carbamazepine alone at 4 mg/kg and 6 mg/kg.In the PTZ model,rosuvastatin alone showed no significant effects on latency,duration of seizure,or mortality.However,rosuvastatin 10 mg/kg combined with valproate 100 mg/kg significantly delayed the onset of seizures,seizure duration and mortality percentage,better than valproate alone at 100 mg/kg.CONCLUSION Rosuvastatin enhanced the anticonvulsant effects of carbamazepine and valproate.Further studies are required to explore the antiepileptic potential of rosuvastatin at various doses,durations,dosage forms,routes and models.展开更多
Objective: To evaluate the bioequivalence (BE) of two fixed-dose combination (FDC) formulations of Rosuvastatin and Ezetimibe: Cresadex® EZE 20/10 mg (Abbott Laboratories) as the reference formulation (R), and Ra...Objective: To evaluate the bioequivalence (BE) of two fixed-dose combination (FDC) formulations of Rosuvastatin and Ezetimibe: Cresadex® EZE 20/10 mg (Abbott Laboratories) as the reference formulation (R), and Racor® Duo 20/10 mg (Laboratorios Leti, S.A.V.) as the test formulation (T). Method: A randomized, single-dose, two-period, two-sequence, open-label, crossover design was employed. Subjects received a single oral dose of either the Test or Reference formulation under fasting conditions, with a 12-day washout period between treatments. Male subjects aged 18 - 45 years with normal health and laboratory values were included. Exclusion criteria encompassed any medical conditions, recent surgery, drug or alcohol use, and hypersensitivity to the study drugs. Blood samples were collected at pre-dose and multiple post-dose time points and analyzed using a validated LC-MS/MS method to quantify Rosuvastatin and Ezetimibe concentrations in plasma. Descriptive statistics were used to summarize pharmacokinetic (PK) parameters. ANOVA was conducted to compare the ln-transformed values of Cmax, AUC0−t, and AUC0−∞. Schuirmann’s two one-sided t-tests were applied to assess bioequivalence (BE). Results: The 90% Confidence Intervals for the ln-transformed ratios of Cmax, AUC0−t, and AUC0−∞ fell within the acceptance range of 80% to 125%, demonstrating bioequivalence between the Test and Reference formulations. Both formulations were well-tolerated, with no serious adverse events reported. Conclusions: The results of this study confirm the bioequivalence of the two tested FDC Rosuvastatin/Ezetimibe formulations: Cresadex® EZE (Abbott Laboratories) and Racor® Duo (Laboratorios Leti, S.A.V.). These findings endorse the therapeutic interchangeability of these products, providing clinicians with greater flexibility in the treatment of hyperlipidemia.展开更多
Objectives: To compare the rate and extent of absorption of Racor® 20 mg (Rosuvastatin calcium 20 mg) tablet of Laboratorios Leti, S.A.V., with Crestor® 20 mg (Rosuvastatin calcium 20 mg) tablet of AstraZene...Objectives: To compare the rate and extent of absorption of Racor® 20 mg (Rosuvastatin calcium 20 mg) tablet of Laboratorios Leti, S.A.V., with Crestor® 20 mg (Rosuvastatin calcium 20 mg) tablet of AstraZeneca, UK Limited in healthy adult human subjects under fasting conditions. Method: This was an open label, analyst blind, balanced, randomized, two-treatment, two-period, two-sequence, single oral dose, crossover, bioequivalence study in healthy, adult, human subjects under fasting condition. Twenty-four (24) subjects were planned as per the protocol and all subjects completed both periods of the study. The concentrations of Rosuvastatin in plasma were quantitated using a validated LC-MS/MS method of analysis and plasma levels were submitted for statistical analysis. Cmax, AUC0-t, AUC0-∞, Tmax, t1/2, Kel (hrs-1), percent AUC extrapolated [100 * (AUC0-∞ - AUC0-t)/AUC0-∞] (AUC_%Extrapobs) were calculated for rosuvastatin in plasma using SAS® version 9.1.3, SAS Institute. Inc. USA.CARY. ANOVA, 90% confidence interval using Schuirmann’s two one-sided test for bioequivalence, power and ratio analysis, for lntransformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞ were computed and reported for Rosuvastatin in plasma for BE. Results: Data showed that 90% confidence intervals for the test/reference geometric mean ratios (GMR) of Cmax (95.01 - 112.66), AUC0-t (93.38 - 111.67) and AUC0-∞ (93.65 - 111.29) were within the BE (80% - 125%) acceptance range. Conclusions: Two products formulation, reference (R) Crestor® (rosuvastatin calcium) of AstraZeneca and test (T), Racor® (rosuvastatin calcium) of Laboratorios Leti S.A.V., with a single dose of 20 mg, under fasting conditions were bioequivalent. No severe, serious or unexpected adverse events (AEs) were reported in this study.展开更多
Background Population aging has become a common concern in the world.coronary heart disease(CHD)is one of the major diseases that lead to the death of the elderly and affect the quality of life.Studies have confirmed ...Background Population aging has become a common concern in the world.coronary heart disease(CHD)is one of the major diseases that lead to the death of the elderly and affect the quality of life.Studies have confirmed that increase in blood lipids is an independent risk factor for the occurrence and development of coronary heart disease.Therefore,adjusting the level of blood lipids effectively has significant value to alleviate the severity,slow the progression and reduce the occurrence of complications of coronary heart disease.Statins can play a role in regulating the blood lipids.Although rosuvastatin is a kind of highly potent statin that is often used at present,the effects of different doses of rosuvastatin on elderly patients with coronary heart disease and hyperlipidemia were seldom reported.Methods In this study,60 elderly patients with coronary heart disease and hyperlipidemia admitted to our hospital from 2021 to July to September 2023 were retrospectively selected.30 patients with 10 mg/d rosuvastatin were assigned to the control group and 30 patients with 20 mg/d rosuvastatin were assigned to the observation group,and their efficacy and safety were compared and analyzed.Results The total effective rate of observation group was 96.67%,which was higher than that of control group 86.67%(P<0.05).Before treatment,there was no significant difference in blood lipid levels between the two groups(P>0.05).After treatment,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL-C)and high density lipoprotein(HDL-C)were lower in the observation group(P<0.05).And there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusions The effect of 20 mg/d of rosuvastatin in the treatment of elderly CHD patients with hyperlipidemia is better than that of 10 mg/d of rosuvastatin,which can effectively regulate the level of blood lipids in the body without causing excessive adverse reactions.[S Chin J Cardiol 2024;25(3):149-155]展开更多
AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis(NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.METHODS: Th...AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis(NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome(Met S) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients receivedlifestyle advice and were treated for a 12 mo period with rosuvastatin(10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid(SUA), high sensitivity C reactive protein(hs CRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values.RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20 th, which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3rd treatment month(ANOVA P < 0.001), while alkaline phosphatase activities by the 6th treatment month(ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced(P < 0.001). Lipid values were normalised by the 3rd treatment month. No patient had Met S by the 9th treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group.CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve Met S within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.展开更多
To evaluate the anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium (DSS)-induced colitis model. METHODSAn acute colitis mouse model was induced b...To evaluate the anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium (DSS)-induced colitis model. METHODSAn acute colitis mouse model was induced by oral administration of 5% DSS in the drinking water for 7 d. In the treated group, rosuvastatin (0.3 mg/kg per day) was administered orally before and after DSS administration for 21 d. On day 21, mice were sacrificed and the colons were removed for macroscopic examination, histology, and Western blot analysis. In the in vitro study, IEC-6 cells were stimulated with 50 ng/mL tumor necrosis factor (TNF)-α and then treated with or without rosuvastatin (2 μmol/L). The levels of reactive oxygen species (ROS), inflammatory mediators, and apoptotic markers were measured. RESULTSIn DSS-induced colitis mice, rosuvastatin treatment significantly reduced the disease activity index and histological damage score compared to untreated mice (P < 0.05). Rosuvastatin also attenuated the DSS-induced increase of 8-hydroxy-2’-deoxyguanosine and NADPH oxidase-1 expression in colon tissue. Multiplex ELISA analysis revealed that rosuvastatin treatment reduced the DSS-induced increase of serum IL-2, IL-4, IL-5, IL-6, IL-12 and IL-17, and G-CSF levels. The increased levels of cleaved caspase-3, caspase-7, and poly (ADP-ribose) polymerase in the DSS group were attenuated by rosuvastatin treatment. In vitro, rosuvastatin significantly reduced the production of ROS, inflammatory mediators and apoptotic markers in TNF-α-treated IEC-6 cells (P < 0.05). CONCLUSIONRosuvastatin had the antioxidant, anti-inflammatory and anti-apoptotic effects in DSS-induced colitis model. Therefore, it might be a candidate anti-inflammatory drug in patients with inflammatory bowel disease.展开更多
Objective： To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 （MMP-2） and tissue inhibitors of matrix metalloproteinase-2 （TIMP-2） and on cell migration of cultur...Objective： To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 （MMP-2） and tissue inhibitors of matrix metalloproteinase-2 （TIMP-2） and on cell migration of cultured rat vascular smooth muscle cells （VSMCs）. Also, to explore whether rosuvastatin can alter the abnormal secretion and activation of MMP-2 and TIMP-2 and migration of VSMCs induced by homocysteine. Methods： Rat VSMCs were incubated with different concentrations of homocysteine （50-5000 μmol/L）. Western blotting and gelatin zymography were used to investigate the expressions and activities of MMP-2 and TIMP-2 in VSMCs in culture medium when induced with homocysteine for 24, 48, and 72 h. Transwell chambers were employed to test the migratory ability of VSMCs when incubated with homocysteine for 48 h. Different concentrations of rosuvastatin （10^-9-10^-5 mol/L） were added when VSMCs were induced with 1 000 pmol/L homocysteine. The expressions and activities of MMP-2 and TIMP-2 were examined after incubating for 24, 48, and 72 h, and the migration of VSMCs was also examined after incubating for 48 h. Results： Homocysteine （50-1000 μmol/L） increased the production and activation of MMP-2 and expression of TIMP-2 in a dose-dependent manner. However, when incubated with 5000 pmol/L homocysteine, the expression of MMP-2 was up-regulated, but its activity was down-regulated. Increased homocysteine-induced production and ac- tivation of MMP-2 were reduced by rosuvastatin in a dose-dependent manner whereas secretion of TIMP-2 was not significantly altered by rosuvastatin. Homocysteine （50-5000 μmol/L） stimulated the migration of VSMCs in a dose-dependent manner, but this effect was eliminated by rosuvastatin. Conclusions： Homocysteine （50-1000 μmol/L） significantly increased the production and activation of MMP-2, the expression of TIMP-2, and the migration of VSMCs in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the excessive expression and acti- vation of MMP-2 and abnormal migration of VSMCs induced by homocysteine.展开更多
We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuv...We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuvastatin has a greater potential compared with other statins to damage the liver is unclear and the involved mechanisms are also unknown. However, rosuvastatin is taken up by hepatocytes more selectively and more efficiently than other statins, and this may reasonably represent an important variable to explain the hepatotoxic potential of rosuvastatin. Our report supports the view that a clinically significant risk of liver toxicity should be considered even when rosuvastatin is given at the range of doses used in common clinical practice.展开更多
AIM： To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS： Ocular hypertension was induced in right eyes of Long-Evans rats （n=30） by cauterization of three episcle...AIM： To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS： Ocular hypertension was induced in right eyes of Long-Evans rats （n=30） by cauterization of three episcleral veins. Left eyes were defined as controls. Rats were divided into five groups： oral rosuvastatin, intravitreal rosuvastatin, oral ＋intravitreal rosuvastatin, intravitreal sham and glaucoma without intervention. Rats were sacrificed at day 14. Retinal ganglion cell （RGC） number was assessed by histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling （TUNEL） staining and the expression of glial fibrillary acidic protein （GFAP） in RGC layer was also examined. RESULTS： A significant intraocular pressure （lOP） elevation was seen （P=0.002）. Elevated lOP resulted in a significant decrease in number of RGCs in group 5 （70.33 ±8.2 cells/mm2） when compared with controls （92.50 ±13.72 cells/mm2; P=0.03）. The RGC number in group 1 （92.4±7.3 cells/mm2） was significantly higher than group 5 （ρ=0.03）. The numbers of RGC in groups 2, 3 （57.3±8.2 cells/mm2, 60.5±12.9 cells/mm2） were comparable with that of group 5 （ρ=0.18 and P=0.31）. The apoptosis rates with TUNEL staining were also parallel to RGC number. Animals with experimentally induced glaucoma showed an increase in retinal GFAP immunoreacUvity. CONCLUSION： Decrease in RGC loss and apoptosis suggest the neuroprotective potential of oral rosuvastatin treatment in a rat model of ocular hypertension. Howeverintravitreal rosuvastatin showed a contrary effect and further studies are required.展开更多
Objective To evaluate whether ursolic acid can inhibit breast cancer resistance protein(BCRP)-mediated transport of rosuvastatin in vivo and in vitro. Methods Firstly, we explored the pharmacokinetics of 5-fluorouraci...Objective To evaluate whether ursolic acid can inhibit breast cancer resistance protein(BCRP)-mediated transport of rosuvastatin in vivo and in vitro. Methods Firstly, we explored the pharmacokinetics of 5-fluorouracil(5-FU, a substrate of BCRP) in rats in the presence or absence of ursolic acid. Secondly, we studied the pharmacokinetics of rosuvastatin in rats in the presence or absence of ursolic acid or Ko143(inhibitor of BCRP). Finially, the concentration-dependent transport of rosuvastatin and the inhibitory effects of ursolic acid and Ko143 were examined in Madin-Darby Canine Kidney(MDCK) Ⅱ-BCRP421CC(wild type) cells and MDCKⅡ-BCRP421AA(mutant type) cells. Results As a result, significant changes in pharmacokinetics parameters of 5-FU were observed in rats following pretreatment with ursolic acid. Both ursolic acid and Ko143 could significantly affect the pharmacokinetics of rosuvastatin. The rosuvastatin transport in the BCRP overexpressing system was increased in a concentration-dependent manner. However, there was no statistical difference in BCRP-mediated transport of rosuvastatin betweent the wild type cells and mutant cells. The same as Ko143, ursolic acid inhibited BCRP-mediated transport of rosuvastatin in vitro. Conclusion Ursolic acid appears to be a potent modulator of BCRP that affects the pharmacokinetic of rosuvastatin in vivo and inhibits the transport of rosuvastatin in vitro.展开更多
Objective: To study the expression quantity of serum miR-146a and miR-146b in patients with acute cerebral infarction before and after the intervention of rosuvastatin and its correlation with toll-like receptor 2 (TL...Objective: To study the expression quantity of serum miR-146a and miR-146b in patients with acute cerebral infarction before and after the intervention of rosuvastatin and its correlation with toll-like receptor 2 (TLR2) and TLR4 signaling pathways. Methods:A total of 65 patients with acute cerebral infarction treated in our hospital from December 2015 to August 2016 were selected for prospective study. They were treated with lipid-lowering rosuvastatin, and peripheral blood samples were collected at 8th week before and after treatment, respectively. Serum was separated and expression quantity of miR-146a and miR-146b and contents of TNF-α, interleukin (IL)-1β, IL-6 and IL-17 were determined. Peripheral blood mononuclear cells were isolated and fluorescence intensities of TLR2, TLR4, myeloid differentiation primary response gene 88 (MyD88), interleukin-1 receptor-associated kinase 1 (IRAK-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) were measured. Results:At 8th week of intervention of rosuvastatin, expression quantity of serum miR-146a [(0.762 ± 0.092)vs. (0.346 ± 0.053)] and miR-146b [(0.714 ± 0.088)vs. (0.317 ± 0.047)] in patients with acute cerebral infarction was significantly higher than those before the intervention. Fluorescence intensities of peripheral blood mononuclear cells such as TLR2 [(10.34 ± 1.27)vs. (16.94 ± 1.94)], TLR4 [(11.37 ± 1.54)vs. (24.35 ± 3.26)], IRAK [(9.34 ± 0.92)vs. (15.32 ± 1.82)], MyD88 [(4.42 ± 0.56) vs. (9.41 ± 1.03)] and NF-kB [(6.65 ± 0.78) vs. (13.49 ± 1.76)] and contents of inflammatory factors such as TNF-α [(64.26 ± 8.29) μg/L vs. (106.39 ± 13.84) μg/L], IL-1β [(37.91 ± 5.24) μg/Lvs. (64.23 ± 8.33) μg/L], IL-6 [(34.28 ± 4.85) ng/Lvs. (82.46 ± 11.97) ng/L] and IL-17 [(56.75 ± 7.49) ng/Lvs. (98.31 ± 11.36) ng/L] of serum were all significantly lower than those before the intervention. Expression quantity of serum miR-146a and miR-146b had a negative correlation with fluorescence intensities of TLR2, TLR4, IRAK, MyD88 and NF-kB. Fluorescence intensities of TLR2 and TLR4 in peripheral blood mononuclear cells had a positive correlation with contents of TNF-α, IL-1β, IL-6 and IL-17 in serum. Conclusions: Treatment with rosuvastatin can up-regulate the expression quantity of serum miR-146a and miR-146b in patients with acute cerebral infarction and further inhibit the secretion of IRAK, MyD88, NF-kB, TNF-α, IL-1β, IL-6 and IL-17 mediated by TLR2 and TLR4.展开更多
AIM： To investigate the protective effect of rosuvastatin on ischemia-reperfusion （I-R）-induced small intestinal injury and inflammation in rats, and to determine the effect of this agent on the expression of endot...AIM： To investigate the protective effect of rosuvastatin on ischemia-reperfusion （I-R）-induced small intestinal injury and inflammation in rats, and to determine the effect of this agent on the expression of endothelial nitric oxide synthase （eNOS） protein. METHODS： Intestinal damage was induced in male Sprague-Dawley rats by clamping both the superior mesenteric artery and the celiac trunk for 30 min, followed by reperfusion for 60 min. Rosuvastatin dissolved in physiological saline was administered intraperitoneally 60 min before ischemia. The severity of the intestinal mucosal injury and inflammation were evaluated by several biochemical markers, as well as by histological findings. The protein levels of eNOS were determined by Western blot. RESULTS： The levels of both intraluminal hemoglobin and protein, as indices of mucosal damage, were significantly increased in the I-R group compared with those in the sham-operated group. These increases, however, were significantly inhibited by treatment with rosuvastatin in a dose-dependent manner. The protective effects of rosuvastatin were also confirmed by histological findings. Exposure of the small intestine to I-R resulted in mucosal inflammation characterized by significant increases in thiobarbituric acid-reactive substances, tissueassociated myeloperoxidase activity, and the mucosal contents of rat cytokine-induced neutrophil chemoattracrant-1 （CINC-1） and tumor necrosis factor-α（TNF-α）. These increases in inflammatory parameters after I-R were significantly inhibited by pretreatment with rosuvo astatin at a dose of 10 mg/kg. Furthermore, mRNA expression of CINC-1 and TNF-α was increased after I-R, and this increase was also inhibited by rosuvastatin. The mucosal protein levels of eNOS decreased during I-R, but were preserved in rats treated with rosuvastatin. CONCLUSION： Rosuvastatin inhibits rat intestinal injury and inflammation induced by I-R, and its protection is associated with the preservation of eNOS protein.展开更多
BACKGROUND:Sepsis is a common cause of death in emergency departments and sepsis-associated encephalopathy(SAE)is a major complication.Rosuvastatin may play a neuroprotective role due to its protective effects on the ...BACKGROUND:Sepsis is a common cause of death in emergency departments and sepsis-associated encephalopathy(SAE)is a major complication.Rosuvastatin may play a neuroprotective role due to its protective effects on the vascular endothelium and its anti-inflammatory functions.Our study aimed to explore the potential protective function of rosuvastatin against SAE.METHODS:Sepsis patients without any neurological dysfunction on admission were prospectively enrolled in the“Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome”study(SAILS trial,ClinicalTrials.gov number:NCT00979121).Patients were divided into rosuvastatin and placebo groups.This is a secondary analysis of the SAILS dataset.Baseline characteristics,therapy outcomes,and adverse drug events were compared between groups.RESULTS:A total of 86 patients were eligible for our study.Of these patients,51 were treated with rosuvastatin.There were significantly fewer cases of SAE in the rosuvastatin group than in the placebo group(32.1%vs.57.1%,P=0.028).However,creatine kinase levels were significantly higher in the rosuvastatin group than in the placebo group(233[22-689]U/L vs.79[12-206]U/L,P=0.034).CONCLUSION:Rosuvastatin appears to have a protective role against SAE but may result in a higher incidence of adverse events.展开更多
To study the protective effect of rosuvastatin on ischemic brain injury and its mechanism, focal cerebral ischemia/reperfusion was induced by occlusion of the middle cerebral artery （MCA） using the intra-luminal fil...To study the protective effect of rosuvastatin on ischemic brain injury and its mechanism, focal cerebral ischemia/reperfusion was induced by occlusion of the middle cerebral artery （MCA） using the intra-luminal filament technique. The cerebral blood flow was monitored with laser-Doppler flowmetry （LDF）. The slices of brain tissue were stained with cresyl-violet. The cerebral volume of infarction and edema were quantified with ImageJ software. The expressions of endothelial NO synthase （eNOS） and activated caspase-3 were detected with Western blot. The inducible NO synthase （iNOS） positive cells were immunohistochemically observed. The results demonstrated that rosuvastatin （20 mg/kg） could remarkably decrease infarct volume and cerebral edema after MCAO 90 min/reperfusion 24 h. Western blots showed that the expression of eNOS in cerebral cortex before and after ischemia was （100±43.3） %, （1668.9± 112.2） % respectively （P〈0.001）, rosuvastatin significantly up-regulated the expression of eNOS in non-ischemic cortex （P〈0.001）, whereas in ischemic cortex of rosuvastatin group the expression of eNOS was （1678.8 ± 121.3） %. There was no expression of activated caspase-3 in non-ischemic cortex, nonetheless the expression of activated caspase-3 increased after ischemia, and rosuvastatin significantly diminished it （P〈0.01）. Immunohistochemistry revealed no iNOS-positive cells in non-ischemic brain area, while in ischemic brain area the number of iNOS positive cells went up, and rosuvastatin could significantly reduced them. Consequently, the mechanisms of rosuvastatin＇s neural protection on ischemic brain injury are to enhance expression of eNOS, to inhibit expression of iNOS and activated caspase-3.展开更多
In the present study,we aimed to investigate the interactions of pharmacokinetics and liver distributions between rosuvastatin and repaglinide in rats.Coadministration of repaglinide（0.5 mg/kg,1 mg/kg and 2 mg/kg） f...In the present study,we aimed to investigate the interactions of pharmacokinetics and liver distributions between rosuvastatin and repaglinide in rats.Coadministration of repaglinide（0.5 mg/kg,1 mg/kg and 2 mg/kg） for 7 d significantly increased the AUC0–24 and Cmax of rosuvastatin（P〈0.01）,but dramatically decreased the CL/F of rosuvastatin（P〈0.01） after a single dose of rosuvastatin（10 mg/kg）.There were no obviously changes in the parameters of Tmax and t1/2.Coadministration of repaglinide also decreased the liver distribution of rosuvastatin（P〈0.01）.Coadministration of rosuvastatin（20 mg/kg） for 7 days significantly increased the AUC0–12 and Cmax of repaglinide（P〈0.05）,and decreased the CL/F of repaglinide（P〈0.01） after a single dose of repaglinide（1 mg/kg）.The liver distribution of repaglinide was also decreased（P〈0.01）.Our animal study indicated that repaglinide could significantly affect the pharmacokinetics and liver distribution of rosuvastatin in rats and vice versa.展开更多
A sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of rosuvastatin in human plasma using gliclazide as ...A sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of rosuvastatin in human plasma using gliclazide as an internal standard (IS). Rosuvastatin and gliclazide in plasma were extracted with ethyl acetate, separated on a C18 reversed phase column, eluted with mobile phase of acetonitrile-methanoic acid (0.1%) (60:40, v/v), ionized by positive ion pneumatically assisted electrospray and detected in the multi-reaction monitoring mode using precursor → product ions of m/z 482.1 → 258.1 for rosuvastatin and m/z 324.2 → 127.2 for IS, respectively. The calibration curve was linear (r2 > 0.99, n = 5) over the concentration range of 0.1 - 60 ng/mL. The speci?city, matrix effect, recovery, sensitivity, linearity, accuracy, precision, and stabilities were validated for rosuvastatin in human plasma. In conclusion, the validation results showed that this method was sensitive, economical and less toxic and it can successfully ful?ll the requirement of bioequivalence study of rosuvastatin calcium tablets in Chinese healthy volunteers.展开更多
Objective:To evaluate the effect of rosuvastatin on the vascular endothelial function and inflammatory cytokine in patients after PCI.Methods:A total of 120 patients with ACS who were admitted in our hospital from Dec...Objective:To evaluate the effect of rosuvastatin on the vascular endothelial function and inflammatory cytokine in patients after PCI.Methods:A total of 120 patients with ACS who were admitted in our hospital from December, 2014 to June, 2016 were included in the study and randomized into the observation group and the control group. PCI was performed in the two groups. The patients in the control group were given routine treatments. On this basis, the patients in the observation group were given rosuvastatin (20 mg) 3 d before operation, every night before sleep, continuously for 1 month. The efficacy was evaluated 24 h and 1 month after operation. Hs-CRP, IL-10, TNF-α, vWF, ET-1, NO, TG, TC, and LDL levels before operation, 24 h and 1 month after operation in the two groups were detected.Results:vWF and ET-1 levels 1 month after operation in the observation group were significantly lower than those in the control group, while NO was significantly higher than that in the control group. hs-CRP, IL-10, and TNF-α 24 h and 1 month after operation in the observation group were significantly lower than those in the control group. TC, TG, and LDL levels 24 h and 1 month after operation in the observation group were significantly lower than those in the control group.Conclusions:Rosuvastatin can effectively reduce the serum inflammatory cytokine level, improve the vascular endothelial function, and decrease the occurrence of thrombus and restenosis in patients with ACS after PCI.展开更多
BACKGROUND Experimental evidence has indicated the benefits of statins for the treatment of postoperative delirium.Previously,clinical trials did not reach definite conclusions on the effects of statins on delirium.So...BACKGROUND Experimental evidence has indicated the benefits of statins for the treatment of postoperative delirium.Previously,clinical trials did not reach definite conclusions on the effects of statins on delirium.Some clinical trials have indicated that statins reduce postoperative delirium and improve outcomes,while some studies have reported negative results.AIM To evaluate whether perioperative rosuvastatin treatment reduces the incidence of delirium and improves clinical outcomes.METHODS This randomized,double-blind,and placebo-controlled trial was conducted in a single center in Jiangsu,China.This study enrolled patients aged greater than 60 years who received general anesthesia during elective operations and provided informed consent.A computer-generated randomization sequence(in a 1:1 ratio)was used to randomly assign patients to receive either rosuvastatin(40 mg/d)or placebo.Participants,care providers,and investigators were all masked to group assignments.The primary endpoint was the incidence of delirium,which was assessed twice daily with the Confusion Assessment Method during the first 7 postoperative days.Analyses were performed on intention-to-treat and safety populations.RESULTS Between January 1,2017 and January 1,2020,3512 patients were assessed.A total of 821 patients were randomly assigned to receive either placebo(n=411)or rosuvastatin(n=410).The incidence of postoperative delirium was significantly lower in the rosuvastatin group[23(5.6%)of 410 patients]than in the placebo group{42(13.5%)of 411 patients[odds ratios(OR)=0.522,95%confidence interval(CI):0.308-0.885;P<0.05]}.No significant difference in 30-d all-cause mortality(6.1%vs 8.7%,OR=0.67,95%CI:0.39-1.2,P=0.147)was observed between the two groups.Rosuvastatin decreased the hospitalization time(13.8±2.5 vs 14.2±2.8,P=0.03)and hospitalization expenses(9.3±2.5 vs 9.8±2.9,P=0.007).No significant differences in abnormal liver enzymes(9.0%vs 7.1%,OR=1.307,95%CI:0.787-2.169,P=0.30)or rhabdomyolysis(0.73%vs 0.24%,OR=3.020,95%CI:0.31-29.2,P=0.37)were observed between the two groups.CONCLUSION The current study suggests that perioperative rosuvastatin treatment reduces the incidence of delirium after an elective operation under general anesthesia.However,the evidence does not reveal that rosuvastatin improves clinical outcomes.The therapy is safe.Further investigation is necessary to fully understand the potential usefulness of rosuvastatin in elderly patients.展开更多
Statins, 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase enzyme inhibitors, are lipid-lowering drugs, often used in the treatment of cardiovascular diseases (hyperlipidemia, atherosclerosis). It has been sho...Statins, 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase enzyme inhibitors, are lipid-lowering drugs, often used in the treatment of cardiovascular diseases (hyperlipidemia, atherosclerosis). It has been shown that statins have antiinflammatory effects independent of their lipid-lowering effects and these anti-inflammatory effects inhibit the inflammation and pain process. This study evaluated the antinociceptive and anti-inflammatory effects of rosuvastatin using the acetic acid writhing, the formalin hind paw, the orofacial formalin and the hot plate tests. The following experimental group were used: control, acute (1 day) and chronic (3 days) after oral gavage with rosuvastatin (3, 10, 30, 100 and 300 mg/kg). Rosuvastatin produced a dose-dependent antinociception, with different potency, in all the tests. Additionally, nitric oxide synthase inhibitors (Abbreviationsand aminoguanidine) were used to assess the nitric oxide participation on this induced rosuvastatin antinociception. The data demonstrated the antinociceptive and anti-inflammatory activity of rosuvastatin in algesiometer models of tonic or phasic pain. These activities seem to be induced by modulation of iNOS expression, a result that may be relevant in the pharmacological treatment of human pain where rosuvastatin and nitric oxide synthase inhibitors must be used.展开更多
文摘BACKGROUND Epilepsy impacts millions of people,with many not responding to existing treatments.Some evidence links neuroinflammatory processes to epilepsy.Statins exhibit anti-inflammatory and neuroprotective properties,potentially offering antiepileptic effects.AIM To evaluate the anticonvulsant effects of rosuvastatin in animal models of epilepsy.METHODS Ninety-six albino mice were divided into 16 groups.In the maximal electroshock seizure(MES)model,eight groups received intraperitoneal vehicle,carbama-zepine,rosuvastatin,or a combination.Outcomes measured included seizure protection[tonic hind limb extension(THLE)],duration of THLE,seizure duration,and mortality.In the pentylenetetrazol(PTZ)model,eight groups were pretreated with vehicle,valproate,rosuvastatin,or a combination,with outcomes measured as seizure latency,seizure duration,and mortality.RESULTS In the MES model,rosuvastatin exhibited protection against THLE in a small percentage of mice.Rosuvastatin shortens the duration of THLE in a dose-dependent manner.However,none of these were statistically significant com-pared to the control group.The combination of rosuvastatin 10 mg/kg with carbamazepine 4 mg/kg resulted in a significant reduction in seizure duration compared to the control group,better than carbamazepine alone at 4 mg/kg and 6 mg/kg.In the PTZ model,rosuvastatin alone showed no significant effects on latency,duration of seizure,or mortality.However,rosuvastatin 10 mg/kg combined with valproate 100 mg/kg significantly delayed the onset of seizures,seizure duration and mortality percentage,better than valproate alone at 100 mg/kg.CONCLUSION Rosuvastatin enhanced the anticonvulsant effects of carbamazepine and valproate.Further studies are required to explore the antiepileptic potential of rosuvastatin at various doses,durations,dosage forms,routes and models.
文摘Objective: To evaluate the bioequivalence (BE) of two fixed-dose combination (FDC) formulations of Rosuvastatin and Ezetimibe: Cresadex® EZE 20/10 mg (Abbott Laboratories) as the reference formulation (R), and Racor® Duo 20/10 mg (Laboratorios Leti, S.A.V.) as the test formulation (T). Method: A randomized, single-dose, two-period, two-sequence, open-label, crossover design was employed. Subjects received a single oral dose of either the Test or Reference formulation under fasting conditions, with a 12-day washout period between treatments. Male subjects aged 18 - 45 years with normal health and laboratory values were included. Exclusion criteria encompassed any medical conditions, recent surgery, drug or alcohol use, and hypersensitivity to the study drugs. Blood samples were collected at pre-dose and multiple post-dose time points and analyzed using a validated LC-MS/MS method to quantify Rosuvastatin and Ezetimibe concentrations in plasma. Descriptive statistics were used to summarize pharmacokinetic (PK) parameters. ANOVA was conducted to compare the ln-transformed values of Cmax, AUC0−t, and AUC0−∞. Schuirmann’s two one-sided t-tests were applied to assess bioequivalence (BE). Results: The 90% Confidence Intervals for the ln-transformed ratios of Cmax, AUC0−t, and AUC0−∞ fell within the acceptance range of 80% to 125%, demonstrating bioequivalence between the Test and Reference formulations. Both formulations were well-tolerated, with no serious adverse events reported. Conclusions: The results of this study confirm the bioequivalence of the two tested FDC Rosuvastatin/Ezetimibe formulations: Cresadex® EZE (Abbott Laboratories) and Racor® Duo (Laboratorios Leti, S.A.V.). These findings endorse the therapeutic interchangeability of these products, providing clinicians with greater flexibility in the treatment of hyperlipidemia.
文摘Objectives: To compare the rate and extent of absorption of Racor® 20 mg (Rosuvastatin calcium 20 mg) tablet of Laboratorios Leti, S.A.V., with Crestor® 20 mg (Rosuvastatin calcium 20 mg) tablet of AstraZeneca, UK Limited in healthy adult human subjects under fasting conditions. Method: This was an open label, analyst blind, balanced, randomized, two-treatment, two-period, two-sequence, single oral dose, crossover, bioequivalence study in healthy, adult, human subjects under fasting condition. Twenty-four (24) subjects were planned as per the protocol and all subjects completed both periods of the study. The concentrations of Rosuvastatin in plasma were quantitated using a validated LC-MS/MS method of analysis and plasma levels were submitted for statistical analysis. Cmax, AUC0-t, AUC0-∞, Tmax, t1/2, Kel (hrs-1), percent AUC extrapolated [100 * (AUC0-∞ - AUC0-t)/AUC0-∞] (AUC_%Extrapobs) were calculated for rosuvastatin in plasma using SAS® version 9.1.3, SAS Institute. Inc. USA.CARY. ANOVA, 90% confidence interval using Schuirmann’s two one-sided test for bioequivalence, power and ratio analysis, for lntransformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞ were computed and reported for Rosuvastatin in plasma for BE. Results: Data showed that 90% confidence intervals for the test/reference geometric mean ratios (GMR) of Cmax (95.01 - 112.66), AUC0-t (93.38 - 111.67) and AUC0-∞ (93.65 - 111.29) were within the BE (80% - 125%) acceptance range. Conclusions: Two products formulation, reference (R) Crestor® (rosuvastatin calcium) of AstraZeneca and test (T), Racor® (rosuvastatin calcium) of Laboratorios Leti S.A.V., with a single dose of 20 mg, under fasting conditions were bioequivalent. No severe, serious or unexpected adverse events (AEs) were reported in this study.
文摘Background Population aging has become a common concern in the world.coronary heart disease(CHD)is one of the major diseases that lead to the death of the elderly and affect the quality of life.Studies have confirmed that increase in blood lipids is an independent risk factor for the occurrence and development of coronary heart disease.Therefore,adjusting the level of blood lipids effectively has significant value to alleviate the severity,slow the progression and reduce the occurrence of complications of coronary heart disease.Statins can play a role in regulating the blood lipids.Although rosuvastatin is a kind of highly potent statin that is often used at present,the effects of different doses of rosuvastatin on elderly patients with coronary heart disease and hyperlipidemia were seldom reported.Methods In this study,60 elderly patients with coronary heart disease and hyperlipidemia admitted to our hospital from 2021 to July to September 2023 were retrospectively selected.30 patients with 10 mg/d rosuvastatin were assigned to the control group and 30 patients with 20 mg/d rosuvastatin were assigned to the observation group,and their efficacy and safety were compared and analyzed.Results The total effective rate of observation group was 96.67%,which was higher than that of control group 86.67%(P<0.05).Before treatment,there was no significant difference in blood lipid levels between the two groups(P>0.05).After treatment,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL-C)and high density lipoprotein(HDL-C)were lower in the observation group(P<0.05).And there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusions The effect of 20 mg/d of rosuvastatin in the treatment of elderly CHD patients with hyperlipidemia is better than that of 10 mg/d of rosuvastatin,which can effectively regulate the level of blood lipids in the body without causing excessive adverse reactions.[S Chin J Cardiol 2024;25(3):149-155]
文摘AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis(NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome(Met S) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients receivedlifestyle advice and were treated for a 12 mo period with rosuvastatin(10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid(SUA), high sensitivity C reactive protein(hs CRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values.RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20 th, which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3rd treatment month(ANOVA P < 0.001), while alkaline phosphatase activities by the 6th treatment month(ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced(P < 0.001). Lipid values were normalised by the 3rd treatment month. No patient had Met S by the 9th treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group.CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve Met S within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.
基金Supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science,ICT and Future Planning,No.2014R1A1A1A05008202
文摘To evaluate the anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium (DSS)-induced colitis model. METHODSAn acute colitis mouse model was induced by oral administration of 5% DSS in the drinking water for 7 d. In the treated group, rosuvastatin (0.3 mg/kg per day) was administered orally before and after DSS administration for 21 d. On day 21, mice were sacrificed and the colons were removed for macroscopic examination, histology, and Western blot analysis. In the in vitro study, IEC-6 cells were stimulated with 50 ng/mL tumor necrosis factor (TNF)-α and then treated with or without rosuvastatin (2 μmol/L). The levels of reactive oxygen species (ROS), inflammatory mediators, and apoptotic markers were measured. RESULTSIn DSS-induced colitis mice, rosuvastatin treatment significantly reduced the disease activity index and histological damage score compared to untreated mice (P < 0.05). Rosuvastatin also attenuated the DSS-induced increase of 8-hydroxy-2’-deoxyguanosine and NADPH oxidase-1 expression in colon tissue. Multiplex ELISA analysis revealed that rosuvastatin treatment reduced the DSS-induced increase of serum IL-2, IL-4, IL-5, IL-6, IL-12 and IL-17, and G-CSF levels. The increased levels of cleaved caspase-3, caspase-7, and poly (ADP-ribose) polymerase in the DSS group were attenuated by rosuvastatin treatment. In vitro, rosuvastatin significantly reduced the production of ROS, inflammatory mediators and apoptotic markers in TNF-α-treated IEC-6 cells (P < 0.05). CONCLUSIONRosuvastatin had the antioxidant, anti-inflammatory and anti-apoptotic effects in DSS-induced colitis model. Therefore, it might be a candidate anti-inflammatory drug in patients with inflammatory bowel disease.
基金Project supported by the Health Ministry Scientific Research Fund of China (No. WKJ2011-2-018)the Zhejiang Provincial Natural Science Foundation of China (No. Y2100535)+3 种基金the Key Social Development Project of Zhejiang Province (No. 2010A23010)the Science and Technology Projects of Shaoxing (No. 2011A23011)the Science and Technology Plan Project of Zhejiang Province (No. 2012C33040)the Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents, China
文摘Objective： To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 （MMP-2） and tissue inhibitors of matrix metalloproteinase-2 （TIMP-2） and on cell migration of cultured rat vascular smooth muscle cells （VSMCs）. Also, to explore whether rosuvastatin can alter the abnormal secretion and activation of MMP-2 and TIMP-2 and migration of VSMCs induced by homocysteine. Methods： Rat VSMCs were incubated with different concentrations of homocysteine （50-5000 μmol/L）. Western blotting and gelatin zymography were used to investigate the expressions and activities of MMP-2 and TIMP-2 in VSMCs in culture medium when induced with homocysteine for 24, 48, and 72 h. Transwell chambers were employed to test the migratory ability of VSMCs when incubated with homocysteine for 48 h. Different concentrations of rosuvastatin （10^-9-10^-5 mol/L） were added when VSMCs were induced with 1 000 pmol/L homocysteine. The expressions and activities of MMP-2 and TIMP-2 were examined after incubating for 24, 48, and 72 h, and the migration of VSMCs was also examined after incubating for 48 h. Results： Homocysteine （50-1000 μmol/L） increased the production and activation of MMP-2 and expression of TIMP-2 in a dose-dependent manner. However, when incubated with 5000 pmol/L homocysteine, the expression of MMP-2 was up-regulated, but its activity was down-regulated. Increased homocysteine-induced production and ac- tivation of MMP-2 were reduced by rosuvastatin in a dose-dependent manner whereas secretion of TIMP-2 was not significantly altered by rosuvastatin. Homocysteine （50-5000 μmol/L） stimulated the migration of VSMCs in a dose-dependent manner, but this effect was eliminated by rosuvastatin. Conclusions： Homocysteine （50-1000 μmol/L） significantly increased the production and activation of MMP-2, the expression of TIMP-2, and the migration of VSMCs in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the excessive expression and acti- vation of MMP-2 and abnormal migration of VSMCs induced by homocysteine.
文摘We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuvastatin has a greater potential compared with other statins to damage the liver is unclear and the involved mechanisms are also unknown. However, rosuvastatin is taken up by hepatocytes more selectively and more efficiently than other statins, and this may reasonably represent an important variable to explain the hepatotoxic potential of rosuvastatin. Our report supports the view that a clinically significant risk of liver toxicity should be considered even when rosuvastatin is given at the range of doses used in common clinical practice.
基金Supported by Gazi University Research and Education Fund
文摘AIM： To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS： Ocular hypertension was induced in right eyes of Long-Evans rats （n=30） by cauterization of three episcleral veins. Left eyes were defined as controls. Rats were divided into five groups： oral rosuvastatin, intravitreal rosuvastatin, oral ＋intravitreal rosuvastatin, intravitreal sham and glaucoma without intervention. Rats were sacrificed at day 14. Retinal ganglion cell （RGC） number was assessed by histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling （TUNEL） staining and the expression of glial fibrillary acidic protein （GFAP） in RGC layer was also examined. RESULTS： A significant intraocular pressure （lOP） elevation was seen （P=0.002）. Elevated lOP resulted in a significant decrease in number of RGCs in group 5 （70.33 ±8.2 cells/mm2） when compared with controls （92.50 ±13.72 cells/mm2; P=0.03）. The RGC number in group 1 （92.4±7.3 cells/mm2） was significantly higher than group 5 （ρ=0.03）. The numbers of RGC in groups 2, 3 （57.3±8.2 cells/mm2, 60.5±12.9 cells/mm2） were comparable with that of group 5 （ρ=0.18 and P=0.31）. The apoptosis rates with TUNEL staining were also parallel to RGC number. Animals with experimentally induced glaucoma showed an increase in retinal GFAP immunoreacUvity. CONCLUSION： Decrease in RGC loss and apoptosis suggest the neuroprotective potential of oral rosuvastatin treatment in a rat model of ocular hypertension. Howeverintravitreal rosuvastatin showed a contrary effect and further studies are required.
基金Supported by the National Natural Science Foundation of China(81202583)the Education Department of Jiangxi Province(GJJ12145)+1 种基金Research Fund Project for Traditional Chinese Medicine of the Health Department of Jiangxi Province(2012A137)the Department of Science and Technology of Jiangxi Province(20151BBG70214)
文摘Objective To evaluate whether ursolic acid can inhibit breast cancer resistance protein(BCRP)-mediated transport of rosuvastatin in vivo and in vitro. Methods Firstly, we explored the pharmacokinetics of 5-fluorouracil(5-FU, a substrate of BCRP) in rats in the presence or absence of ursolic acid. Secondly, we studied the pharmacokinetics of rosuvastatin in rats in the presence or absence of ursolic acid or Ko143(inhibitor of BCRP). Finially, the concentration-dependent transport of rosuvastatin and the inhibitory effects of ursolic acid and Ko143 were examined in Madin-Darby Canine Kidney(MDCK) Ⅱ-BCRP421CC(wild type) cells and MDCKⅡ-BCRP421AA(mutant type) cells. Results As a result, significant changes in pharmacokinetics parameters of 5-FU were observed in rats following pretreatment with ursolic acid. Both ursolic acid and Ko143 could significantly affect the pharmacokinetics of rosuvastatin. The rosuvastatin transport in the BCRP overexpressing system was increased in a concentration-dependent manner. However, there was no statistical difference in BCRP-mediated transport of rosuvastatin betweent the wild type cells and mutant cells. The same as Ko143, ursolic acid inhibited BCRP-mediated transport of rosuvastatin in vitro. Conclusion Ursolic acid appears to be a potent modulator of BCRP that affects the pharmacokinetic of rosuvastatin in vivo and inhibits the transport of rosuvastatin in vitro.
文摘Objective: To study the expression quantity of serum miR-146a and miR-146b in patients with acute cerebral infarction before and after the intervention of rosuvastatin and its correlation with toll-like receptor 2 (TLR2) and TLR4 signaling pathways. Methods:A total of 65 patients with acute cerebral infarction treated in our hospital from December 2015 to August 2016 were selected for prospective study. They were treated with lipid-lowering rosuvastatin, and peripheral blood samples were collected at 8th week before and after treatment, respectively. Serum was separated and expression quantity of miR-146a and miR-146b and contents of TNF-α, interleukin (IL)-1β, IL-6 and IL-17 were determined. Peripheral blood mononuclear cells were isolated and fluorescence intensities of TLR2, TLR4, myeloid differentiation primary response gene 88 (MyD88), interleukin-1 receptor-associated kinase 1 (IRAK-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) were measured. Results:At 8th week of intervention of rosuvastatin, expression quantity of serum miR-146a [(0.762 ± 0.092)vs. (0.346 ± 0.053)] and miR-146b [(0.714 ± 0.088)vs. (0.317 ± 0.047)] in patients with acute cerebral infarction was significantly higher than those before the intervention. Fluorescence intensities of peripheral blood mononuclear cells such as TLR2 [(10.34 ± 1.27)vs. (16.94 ± 1.94)], TLR4 [(11.37 ± 1.54)vs. (24.35 ± 3.26)], IRAK [(9.34 ± 0.92)vs. (15.32 ± 1.82)], MyD88 [(4.42 ± 0.56) vs. (9.41 ± 1.03)] and NF-kB [(6.65 ± 0.78) vs. (13.49 ± 1.76)] and contents of inflammatory factors such as TNF-α [(64.26 ± 8.29) μg/L vs. (106.39 ± 13.84) μg/L], IL-1β [(37.91 ± 5.24) μg/Lvs. (64.23 ± 8.33) μg/L], IL-6 [(34.28 ± 4.85) ng/Lvs. (82.46 ± 11.97) ng/L] and IL-17 [(56.75 ± 7.49) ng/Lvs. (98.31 ± 11.36) ng/L] of serum were all significantly lower than those before the intervention. Expression quantity of serum miR-146a and miR-146b had a negative correlation with fluorescence intensities of TLR2, TLR4, IRAK, MyD88 and NF-kB. Fluorescence intensities of TLR2 and TLR4 in peripheral blood mononuclear cells had a positive correlation with contents of TNF-α, IL-1β, IL-6 and IL-17 in serum. Conclusions: Treatment with rosuvastatin can up-regulate the expression quantity of serum miR-146a and miR-146b in patients with acute cerebral infarction and further inhibit the secretion of IRAK, MyD88, NF-kB, TNF-α, IL-1β, IL-6 and IL-17 mediated by TLR2 and TLR4.
文摘AIM： To investigate the protective effect of rosuvastatin on ischemia-reperfusion （I-R）-induced small intestinal injury and inflammation in rats, and to determine the effect of this agent on the expression of endothelial nitric oxide synthase （eNOS） protein. METHODS： Intestinal damage was induced in male Sprague-Dawley rats by clamping both the superior mesenteric artery and the celiac trunk for 30 min, followed by reperfusion for 60 min. Rosuvastatin dissolved in physiological saline was administered intraperitoneally 60 min before ischemia. The severity of the intestinal mucosal injury and inflammation were evaluated by several biochemical markers, as well as by histological findings. The protein levels of eNOS were determined by Western blot. RESULTS： The levels of both intraluminal hemoglobin and protein, as indices of mucosal damage, were significantly increased in the I-R group compared with those in the sham-operated group. These increases, however, were significantly inhibited by treatment with rosuvastatin in a dose-dependent manner. The protective effects of rosuvastatin were also confirmed by histological findings. Exposure of the small intestine to I-R resulted in mucosal inflammation characterized by significant increases in thiobarbituric acid-reactive substances, tissueassociated myeloperoxidase activity, and the mucosal contents of rat cytokine-induced neutrophil chemoattracrant-1 （CINC-1） and tumor necrosis factor-α（TNF-α）. These increases in inflammatory parameters after I-R were significantly inhibited by pretreatment with rosuvo astatin at a dose of 10 mg/kg. Furthermore, mRNA expression of CINC-1 and TNF-α was increased after I-R, and this increase was also inhibited by rosuvastatin. The mucosal protein levels of eNOS decreased during I-R, but were preserved in rats treated with rosuvastatin. CONCLUSION： Rosuvastatin inhibits rat intestinal injury and inflammation induced by I-R, and its protection is associated with the preservation of eNOS protein.
基金This research received funding from the CAMS Innovation Fund for Medical Sciences(CIFMS)(2020-I2M-C&T-B-014,2021-I2M-1-020).
文摘BACKGROUND:Sepsis is a common cause of death in emergency departments and sepsis-associated encephalopathy(SAE)is a major complication.Rosuvastatin may play a neuroprotective role due to its protective effects on the vascular endothelium and its anti-inflammatory functions.Our study aimed to explore the potential protective function of rosuvastatin against SAE.METHODS:Sepsis patients without any neurological dysfunction on admission were prospectively enrolled in the“Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome”study(SAILS trial,ClinicalTrials.gov number:NCT00979121).Patients were divided into rosuvastatin and placebo groups.This is a secondary analysis of the SAILS dataset.Baseline characteristics,therapy outcomes,and adverse drug events were compared between groups.RESULTS:A total of 86 patients were eligible for our study.Of these patients,51 were treated with rosuvastatin.There were significantly fewer cases of SAE in the rosuvastatin group than in the placebo group(32.1%vs.57.1%,P=0.028).However,creatine kinase levels were significantly higher in the rosuvastatin group than in the placebo group(233[22-689]U/L vs.79[12-206]U/L,P=0.034).CONCLUSION:Rosuvastatin appears to have a protective role against SAE but may result in a higher incidence of adverse events.
基金This project was supported by a grant from National Natural Sciences Foundation of China (No. 30472234), and the National Center of Competence in Research Neural Plastic-ity and Repair of Switzerland (3200B0-100790/1).
文摘To study the protective effect of rosuvastatin on ischemic brain injury and its mechanism, focal cerebral ischemia/reperfusion was induced by occlusion of the middle cerebral artery （MCA） using the intra-luminal filament technique. The cerebral blood flow was monitored with laser-Doppler flowmetry （LDF）. The slices of brain tissue were stained with cresyl-violet. The cerebral volume of infarction and edema were quantified with ImageJ software. The expressions of endothelial NO synthase （eNOS） and activated caspase-3 were detected with Western blot. The inducible NO synthase （iNOS） positive cells were immunohistochemically observed. The results demonstrated that rosuvastatin （20 mg/kg） could remarkably decrease infarct volume and cerebral edema after MCAO 90 min/reperfusion 24 h. Western blots showed that the expression of eNOS in cerebral cortex before and after ischemia was （100±43.3） %, （1668.9± 112.2） % respectively （P〈0.001）, rosuvastatin significantly up-regulated the expression of eNOS in non-ischemic cortex （P〈0.001）, whereas in ischemic cortex of rosuvastatin group the expression of eNOS was （1678.8 ± 121.3） %. There was no expression of activated caspase-3 in non-ischemic cortex, nonetheless the expression of activated caspase-3 increased after ischemia, and rosuvastatin significantly diminished it （P〈0.01）. Immunohistochemistry revealed no iNOS-positive cells in non-ischemic brain area, while in ischemic brain area the number of iNOS positive cells went up, and rosuvastatin could significantly reduced them. Consequently, the mechanisms of rosuvastatin＇s neural protection on ischemic brain injury are to enhance expression of eNOS, to inhibit expression of iNOS and activated caspase-3.
文摘In the present study,we aimed to investigate the interactions of pharmacokinetics and liver distributions between rosuvastatin and repaglinide in rats.Coadministration of repaglinide（0.5 mg/kg,1 mg/kg and 2 mg/kg） for 7 d significantly increased the AUC0–24 and Cmax of rosuvastatin（P〈0.01）,but dramatically decreased the CL/F of rosuvastatin（P〈0.01） after a single dose of rosuvastatin（10 mg/kg）.There were no obviously changes in the parameters of Tmax and t1/2.Coadministration of repaglinide also decreased the liver distribution of rosuvastatin（P〈0.01）.Coadministration of rosuvastatin（20 mg/kg） for 7 days significantly increased the AUC0–12 and Cmax of repaglinide（P〈0.05）,and decreased the CL/F of repaglinide（P〈0.01） after a single dose of repaglinide（1 mg/kg）.The liver distribution of repaglinide was also decreased（P〈0.01）.Our animal study indicated that repaglinide could significantly affect the pharmacokinetics and liver distribution of rosuvastatin in rats and vice versa.
文摘A sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of rosuvastatin in human plasma using gliclazide as an internal standard (IS). Rosuvastatin and gliclazide in plasma were extracted with ethyl acetate, separated on a C18 reversed phase column, eluted with mobile phase of acetonitrile-methanoic acid (0.1%) (60:40, v/v), ionized by positive ion pneumatically assisted electrospray and detected in the multi-reaction monitoring mode using precursor → product ions of m/z 482.1 → 258.1 for rosuvastatin and m/z 324.2 → 127.2 for IS, respectively. The calibration curve was linear (r2 > 0.99, n = 5) over the concentration range of 0.1 - 60 ng/mL. The speci?city, matrix effect, recovery, sensitivity, linearity, accuracy, precision, and stabilities were validated for rosuvastatin in human plasma. In conclusion, the validation results showed that this method was sensitive, economical and less toxic and it can successfully ful?ll the requirement of bioequivalence study of rosuvastatin calcium tablets in Chinese healthy volunteers.
文摘Objective:To evaluate the effect of rosuvastatin on the vascular endothelial function and inflammatory cytokine in patients after PCI.Methods:A total of 120 patients with ACS who were admitted in our hospital from December, 2014 to June, 2016 were included in the study and randomized into the observation group and the control group. PCI was performed in the two groups. The patients in the control group were given routine treatments. On this basis, the patients in the observation group were given rosuvastatin (20 mg) 3 d before operation, every night before sleep, continuously for 1 month. The efficacy was evaluated 24 h and 1 month after operation. Hs-CRP, IL-10, TNF-α, vWF, ET-1, NO, TG, TC, and LDL levels before operation, 24 h and 1 month after operation in the two groups were detected.Results:vWF and ET-1 levels 1 month after operation in the observation group were significantly lower than those in the control group, while NO was significantly higher than that in the control group. hs-CRP, IL-10, and TNF-α 24 h and 1 month after operation in the observation group were significantly lower than those in the control group. TC, TG, and LDL levels 24 h and 1 month after operation in the observation group were significantly lower than those in the control group.Conclusions:Rosuvastatin can effectively reduce the serum inflammatory cytokine level, improve the vascular endothelial function, and decrease the occurrence of thrombus and restenosis in patients with ACS after PCI.
文摘BACKGROUND Experimental evidence has indicated the benefits of statins for the treatment of postoperative delirium.Previously,clinical trials did not reach definite conclusions on the effects of statins on delirium.Some clinical trials have indicated that statins reduce postoperative delirium and improve outcomes,while some studies have reported negative results.AIM To evaluate whether perioperative rosuvastatin treatment reduces the incidence of delirium and improves clinical outcomes.METHODS This randomized,double-blind,and placebo-controlled trial was conducted in a single center in Jiangsu,China.This study enrolled patients aged greater than 60 years who received general anesthesia during elective operations and provided informed consent.A computer-generated randomization sequence(in a 1:1 ratio)was used to randomly assign patients to receive either rosuvastatin(40 mg/d)or placebo.Participants,care providers,and investigators were all masked to group assignments.The primary endpoint was the incidence of delirium,which was assessed twice daily with the Confusion Assessment Method during the first 7 postoperative days.Analyses were performed on intention-to-treat and safety populations.RESULTS Between January 1,2017 and January 1,2020,3512 patients were assessed.A total of 821 patients were randomly assigned to receive either placebo(n=411)or rosuvastatin(n=410).The incidence of postoperative delirium was significantly lower in the rosuvastatin group[23(5.6%)of 410 patients]than in the placebo group{42(13.5%)of 411 patients[odds ratios(OR)=0.522,95%confidence interval(CI):0.308-0.885;P<0.05]}.No significant difference in 30-d all-cause mortality(6.1%vs 8.7%,OR=0.67,95%CI:0.39-1.2,P=0.147)was observed between the two groups.Rosuvastatin decreased the hospitalization time(13.8±2.5 vs 14.2±2.8,P=0.03)and hospitalization expenses(9.3±2.5 vs 9.8±2.9,P=0.007).No significant differences in abnormal liver enzymes(9.0%vs 7.1%,OR=1.307,95%CI:0.787-2.169,P=0.30)or rhabdomyolysis(0.73%vs 0.24%,OR=3.020,95%CI:0.31-29.2,P=0.37)were observed between the two groups.CONCLUSION The current study suggests that perioperative rosuvastatin treatment reduces the incidence of delirium after an elective operation under general anesthesia.However,the evidence does not reveal that rosuvastatin improves clinical outcomes.The therapy is safe.Further investigation is necessary to fully understand the potential usefulness of rosuvastatin in elderly patients.
文摘Statins, 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase enzyme inhibitors, are lipid-lowering drugs, often used in the treatment of cardiovascular diseases (hyperlipidemia, atherosclerosis). It has been shown that statins have antiinflammatory effects independent of their lipid-lowering effects and these anti-inflammatory effects inhibit the inflammation and pain process. This study evaluated the antinociceptive and anti-inflammatory effects of rosuvastatin using the acetic acid writhing, the formalin hind paw, the orofacial formalin and the hot plate tests. The following experimental group were used: control, acute (1 day) and chronic (3 days) after oral gavage with rosuvastatin (3, 10, 30, 100 and 300 mg/kg). Rosuvastatin produced a dose-dependent antinociception, with different potency, in all the tests. Additionally, nitric oxide synthase inhibitors (Abbreviationsand aminoguanidine) were used to assess the nitric oxide participation on this induced rosuvastatin antinociception. The data demonstrated the antinociceptive and anti-inflammatory activity of rosuvastatin in algesiometer models of tonic or phasic pain. These activities seem to be induced by modulation of iNOS expression, a result that may be relevant in the pharmacological treatment of human pain where rosuvastatin and nitric oxide synthase inhibitors must be used.
