Therapeutic experiments are commonly performed on laboratory animals to inves-tigate the possible mechanism(s)of action of toxic agents as well as drugs or sub-stances under consideration.The use of toxins in laborato...Therapeutic experiments are commonly performed on laboratory animals to inves-tigate the possible mechanism(s)of action of toxic agents as well as drugs or sub-stances under consideration.The use of toxins in laboratory animal models,including rats,is intended to cause toxicity.This study aimed to investigate different models of hepatotoxicity and nephrotoxicity in laboratory animals to help researchers advance their research goals.The current narrative review used databases such as Medline,Web of Science,Scopus,and Embase and appropriate keywords until June 2021.Nephrotoxicity and hepatotoxicity models derived from some toxic agents such as cisplatin,acetaminophen,doxorubicin,some anticancer drugs,and other materials through various signaling pathways are investigated.To understand the models of renal or hepatotoxicity in laboratory animals,we have provided a list of toxic agents and their toxicity procedures in this review.展开更多
Inflammatory processes and proinflammatory cytokines have a key role in the cellular processes of neurodegenerative diseases and are linked to the pathogenesis of functional and mental health disorders.Tumor necrosis ...Inflammatory processes and proinflammatory cytokines have a key role in the cellular processes of neurodegenerative diseases and are linked to the pathogenesis of functional and mental health disorders.Tumor necrosis factor alpha has been reported to play a major role in the central nervous system in Alzheimer’s disease,Parkinson’s disease and amyotrophic lateral sclerosis and many other neurodegenerative diseases.Therefore,a potent proinflammatory/proapoptotic tumor necrosis factor alpha could be a strong candidate for targeted therapy.Plant derivatives have now become promising candidates as therapeutic agents because of their antioxidant and chemical characteristics,and anti-inflammatory features.Recently,phytochemicals including flavonoids,terpenoids,alkaloids,and lignans have generated interest as tumor necrosis factor alpha inhibitor candidates for a number of diseases involving inflammation within the nervous system.In this review,we discuss how phytochemicals as tumor necrosis factor alpha inhibitors are a therapeutic strategy targeting neurodegeneration.展开更多
Neurodegenerative diseases(NDs)are a growing health problem associated with a high burden due to destructive and longterm clinical effects.Cellular aggregations of misfolded proteins are the most common pathological h...Neurodegenerative diseases(NDs)are a growing health problem associated with a high burden due to destructive and longterm clinical effects.Cellular aggregations of misfolded proteins are the most common pathological hallmark of many late-onset NDs called proteinopathies including Parkinson’s disease(PD),Alzheimer’s disease(AD),tauopathies,amyotrophic lateral sclerosis(ALS),and polyglutamine(polyQ)expansion diseases such as Huntington’s disease(HD)and various spinocerebellar ataxias(SCA)such as SCA3(Renna et al.,2010).Misfolded proteins can be generated by posttranslational conjugation(e.g.,hyperphosphorylated tau in AD),or endoproteolytic cleavage(e.g.,amyloidβpeptides)or genetic mutations in specific proteins(such as HTT in HD,α-synuclein in PD,PrPC in prion disease and SOD1 and TDP-43 in ALS)leading to the formation of oligomers.展开更多
Objective:To explore the effect of ethyl acetate gum resin extract of Boswellia serrata on lipopolysaccharide(LPS)induced inflammation and oxidative damage in hepatic and renal tissues of rats.Methods:The rats were di...Objective:To explore the effect of ethyl acetate gum resin extract of Boswellia serrata on lipopolysaccharide(LPS)induced inflammation and oxidative damage in hepatic and renal tissues of rats.Methods:The rats were divided into four groups:control,LPS,LPS+Boswellia serrata extracts(100 mg/kg and 200 mg/kg).LPS(1 mg/kg)and the extract(100 and 200 mg/kg,30 min before LPS)were administered intraperitoneally for 3 weeks.The levels of liver enzymes,albumin,total protein,creatinine,blood urea nitrogen(BUN),interleukin(IL)-6,malondialdehyde(MDA),and total thiol groups and superoxide dismutase(SOD)and catalase(CAT)activities were measured.Results:The levels of liver enzymes,creatinine,and BUN,IL-6,MDA in the LPS group were markedly increased(P<0.001)while albumin,total protein,and total thiol concentration,as well as SOD and CAT activities,were decreased compared with the control group(P<0.05 or 0.01).Boswellia serrata extracts diminished the levels of liver enzymes,creatinine,BUN,IL-6,and MDA(P<0.01 and P<0.001),and elevated the concentration of total protein and total thiol and SOD and CAT activities(P<0.05 or 0.01).Conclusions:The ethyl acetate gum resin extract of Boswellia serrata reduces LPS-induced inflammatory reactions and oxidative damage,thus ameliorating hepatic and renal function.展开更多
As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative str...As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.展开更多
Background:The dorsomedial periaqueductal gray(dmPAG)is a mesencephalic area and has numerous functions including cardiovascular regulation.Because nitric oxide(NO)is present in the dmPAG,here we investigate,the proba...Background:The dorsomedial periaqueductal gray(dmPAG)is a mesencephalic area and has numerous functions including cardiovascular regulation.Because nitric oxide(NO)is present in the dmPAG,here we investigate,the probable cardiovascular effect of NO in the dmPAG.Methods:Five groups(n=6 for each group)were used as follows:(1)control;(2)L-NAME(N^(G)-nitro-L-arginine methyl ester,a NO synthase inhibitor,90 nmol);(3)Larginine(L-Arg,a precursor for NO,60 nmol);(4)Sodium nitroprusside(SNP,a NO donor,27 nmol);and(5)L-Arg+L-NAME.The cardiovascular parameters were recorded by a Power Lab device after cannulation of the femoral artery.Drugs were injected using a stereotaxic instrument.The changes(Δ)in systolic blood pressure(SBP),mean arterial pressure(MAP),and heart rate(HR)were calculated at different times and compared to the control group.Results:Microinjection of L-NAME significantly increased ΔSBP,ΔMAP,and ΔHR more than saline(from p<0.05 to p<0.001).L-Arg only significantly increased ΔHR(p<0.05).In the L-Arg+L-NAME group,the above parameters also significantly increased(from p<0.01 to p<0.05)but not as significantly as with L-NAME alone.Microinjection of SNP significantly decreased ΔSBP and ΔMAP more than in the control and L-NAME groups(from p<0.01 to p<0.001),but ΔHR did not change significantly.Conclusion:The results indicated that NO in dmPAG has an inhibitory effect on cardiovascular responses in anesthetized rats.展开更多
Background:Zataria multiflora and carvacrol showed various pharmacological prop-erties including anti-inflammatory and anti-oxidant effects.However,up to now no studies have explored its potential benefits in ameliora...Background:Zataria multiflora and carvacrol showed various pharmacological prop-erties including anti-inflammatory and anti-oxidant effects.However,up to now no studies have explored its potential benefits in ameliorating sepsis-induced aortic and cardiac injury.Thus,this study aimed to investigate the effects of Z.multiflora and carvacrol on nitric oxide(NO)and oxidative stress indicators in lipopolysaccharide(LPS)-induced aortic and cardiac injury.Methods:Adult male Wistar rats were assigned to:Control,lipopolysaccharide(LPS)(1 mg/kg,intraperitoneal(i.p.)),and Z.multiflora hydro-ethanolic extract(ZME,50–200 mg/kg,oral)-and carvacrol(25–100 mg/kg,oral)-treated groups.LPS was in-jected daily for 14 days.Treatment with ZME and carvacrol started 3 days before LPS administration and treatment continued during LPS administration.At the end of the study,the levels of malondialdehyde(MDA),NO,thiols,and antioxidant enzymes were evaluated.Results:Our findings showed a significant reduction in the levels of superoxide dis-mutase(SOD),catalase(CAT),and thiols in the LPS group,which were restored by ZME and carvacrol.Furthermore,ZME and carvacrol decreased MDA and NO in car-diac and aortic tissues of LPS-injected rats.Conclusions:The results suggest protective effects of ZME and carvacrol on LPS-induced cardiovascular injury via improved redox hemostasis and attenuated NO pro-duction.However,additional studies are needed to elucidate the effects of ZME and its constituents on inflammatory responses mediated by LPS.展开更多
BACKGROUND Cardiac syndrome X(CSX)is characterized by persistent angina with normal coronary arteries.Several pathophysiologic mechanisms have been introduced,particularly Helicobacter pylori(H.pylori)infection.AIM To...BACKGROUND Cardiac syndrome X(CSX)is characterized by persistent angina with normal coronary arteries.Several pathophysiologic mechanisms have been introduced,particularly Helicobacter pylori(H.pylori)infection.AIM To investigate the association between H.pylori infection and CSX.METHODS All studies related to H.pylori infection and CSX were evaluated by comprehensive searches of global databases such as ISI Web of Knowledge,PubMed,Scopus,EMBASE,and Google scholar.Statistical analyses of selected articles were evaluated based on the summary odds ratio(OR).Finally,heterogeneity and publication bias were estimated using the I2 statistic and Cochrane Q-test as well as Begg’s and Egger’s tests.RESULTS A total of 11 studies met our inclusion criteria and 1435 patients(63%female,and 37%male)were reviewed.A significant association was observed between female patients and this syndrome(P=0.02).Our results showed a positive association between infection with this pathogen and presence of CSX(OR:5.65;95%confidence interval[CI]:4.17-7.64;I2:82.20).However,no significant association was observed with cagA-positive H. pylori strains and this syndrome (OR: 0.97;0.56-1.70 with 95%CI). Given the heterogeneity and publication bias, the resultsneed to confirmed by further prospective investigation.CONCLUSIONBased on our results, H. pylori infection is associated with an increased risk ofCSX. This bacterium appears to play a major role in the pathogenesis of CXS byinducing persistent inflammation.展开更多
Objective:To investigate the effect and safety of phytosomal curcumin supplementation on patients with migraine.Methods:In this randomized,double-blind and placebo-controlled trial,70 patients suffered from migraine w...Objective:To investigate the effect and safety of phytosomal curcumin supplementation on patients with migraine.Methods:In this randomized,double-blind and placebo-controlled trial,70 patients suffered from migraine without aura were randomized into 2 groups to receive 250 mg/d of phytosomal curcumin(intervention group)or maltodextrin(placebo group)for 8 weeks,35 cases per group.All patients in both groups received their standard treatment and common medications.The severity,duration,frequency of headaches,quality of life(QoL),mental status,headache impact,and sleep quality of patients were assessed before and after treatment.Adverse effects were also assessed.Results:Sixty-five patients completed the trial(33 in the intervention group and 32 in the placebo group).Phytosomal curcumin supplementation significantly reduced severity,duration and frequency of migraine attacks,stress score,and headache impact,and improved QoL and sleep quality of patients in the intervention group,compared with the placebo group(P<0.05 or P<0.01).However,it had no significant effect on depression and anxiety scores in the intervention group,compared with the placebo group(P>0.05).No adverse effects had been reported in response to the intervention.Conclusion:Phytosomal curcumin as a safe supplement had a beneficial effect on migraine symptoms,stress level,as well as the sleep quality and QoL in patients with migraine.(Trial registration No.IRCT20201129049534N2)展开更多
文摘Therapeutic experiments are commonly performed on laboratory animals to inves-tigate the possible mechanism(s)of action of toxic agents as well as drugs or sub-stances under consideration.The use of toxins in laboratory animal models,including rats,is intended to cause toxicity.This study aimed to investigate different models of hepatotoxicity and nephrotoxicity in laboratory animals to help researchers advance their research goals.The current narrative review used databases such as Medline,Web of Science,Scopus,and Embase and appropriate keywords until June 2021.Nephrotoxicity and hepatotoxicity models derived from some toxic agents such as cisplatin,acetaminophen,doxorubicin,some anticancer drugs,and other materials through various signaling pathways are investigated.To understand the models of renal or hepatotoxicity in laboratory animals,we have provided a list of toxic agents and their toxicity procedures in this review.
文摘Inflammatory processes and proinflammatory cytokines have a key role in the cellular processes of neurodegenerative diseases and are linked to the pathogenesis of functional and mental health disorders.Tumor necrosis factor alpha has been reported to play a major role in the central nervous system in Alzheimer’s disease,Parkinson’s disease and amyotrophic lateral sclerosis and many other neurodegenerative diseases.Therefore,a potent proinflammatory/proapoptotic tumor necrosis factor alpha could be a strong candidate for targeted therapy.Plant derivatives have now become promising candidates as therapeutic agents because of their antioxidant and chemical characteristics,and anti-inflammatory features.Recently,phytochemicals including flavonoids,terpenoids,alkaloids,and lignans have generated interest as tumor necrosis factor alpha inhibitor candidates for a number of diseases involving inflammation within the nervous system.In this review,we discuss how phytochemicals as tumor necrosis factor alpha inhibitors are a therapeutic strategy targeting neurodegeneration.
文摘Neurodegenerative diseases(NDs)are a growing health problem associated with a high burden due to destructive and longterm clinical effects.Cellular aggregations of misfolded proteins are the most common pathological hallmark of many late-onset NDs called proteinopathies including Parkinson’s disease(PD),Alzheimer’s disease(AD),tauopathies,amyotrophic lateral sclerosis(ALS),and polyglutamine(polyQ)expansion diseases such as Huntington’s disease(HD)and various spinocerebellar ataxias(SCA)such as SCA3(Renna et al.,2010).Misfolded proteins can be generated by posttranslational conjugation(e.g.,hyperphosphorylated tau in AD),or endoproteolytic cleavage(e.g.,amyloidβpeptides)or genetic mutations in specific proteins(such as HTT in HD,α-synuclein in PD,PrPC in prion disease and SOD1 and TDP-43 in ALS)leading to the formation of oligomers.
文摘Objective:To explore the effect of ethyl acetate gum resin extract of Boswellia serrata on lipopolysaccharide(LPS)induced inflammation and oxidative damage in hepatic and renal tissues of rats.Methods:The rats were divided into four groups:control,LPS,LPS+Boswellia serrata extracts(100 mg/kg and 200 mg/kg).LPS(1 mg/kg)and the extract(100 and 200 mg/kg,30 min before LPS)were administered intraperitoneally for 3 weeks.The levels of liver enzymes,albumin,total protein,creatinine,blood urea nitrogen(BUN),interleukin(IL)-6,malondialdehyde(MDA),and total thiol groups and superoxide dismutase(SOD)and catalase(CAT)activities were measured.Results:The levels of liver enzymes,creatinine,and BUN,IL-6,MDA in the LPS group were markedly increased(P<0.001)while albumin,total protein,and total thiol concentration,as well as SOD and CAT activities,were decreased compared with the control group(P<0.05 or 0.01).Boswellia serrata extracts diminished the levels of liver enzymes,creatinine,BUN,IL-6,and MDA(P<0.01 and P<0.001),and elevated the concentration of total protein and total thiol and SOD and CAT activities(P<0.05 or 0.01).Conclusions:The ethyl acetate gum resin extract of Boswellia serrata reduces LPS-induced inflammatory reactions and oxidative damage,thus ameliorating hepatic and renal function.
基金National Natural Science Foundation of China[82274366]The National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine:Multi-dimensional Evaluation and Multidisciplinary Innovation Team of Southwest Traditional Chinese Medicine Resources[ZYYCXTD-D-202209]+2 种基金The Youth Talent Promotion Project of China Association of Chinese Medicine[2021-QNRC2-A09]The Major Project of Sichuan Provincial Administration of Traditional Chinese Medicine(2023ZD01)the financial support from the Indian Council of Medical Research(ICMR),New Delhi,India,through Extramural Research Grants.
文摘As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.
文摘Background:The dorsomedial periaqueductal gray(dmPAG)is a mesencephalic area and has numerous functions including cardiovascular regulation.Because nitric oxide(NO)is present in the dmPAG,here we investigate,the probable cardiovascular effect of NO in the dmPAG.Methods:Five groups(n=6 for each group)were used as follows:(1)control;(2)L-NAME(N^(G)-nitro-L-arginine methyl ester,a NO synthase inhibitor,90 nmol);(3)Larginine(L-Arg,a precursor for NO,60 nmol);(4)Sodium nitroprusside(SNP,a NO donor,27 nmol);and(5)L-Arg+L-NAME.The cardiovascular parameters were recorded by a Power Lab device after cannulation of the femoral artery.Drugs were injected using a stereotaxic instrument.The changes(Δ)in systolic blood pressure(SBP),mean arterial pressure(MAP),and heart rate(HR)were calculated at different times and compared to the control group.Results:Microinjection of L-NAME significantly increased ΔSBP,ΔMAP,and ΔHR more than saline(from p<0.05 to p<0.001).L-Arg only significantly increased ΔHR(p<0.05).In the L-Arg+L-NAME group,the above parameters also significantly increased(from p<0.01 to p<0.05)but not as significantly as with L-NAME alone.Microinjection of SNP significantly decreased ΔSBP and ΔMAP more than in the control and L-NAME groups(from p<0.01 to p<0.001),but ΔHR did not change significantly.Conclusion:The results indicated that NO in dmPAG has an inhibitory effect on cardiovascular responses in anesthetized rats.
基金All experimental procedures pursued the relevant guidelines and regulations of the National Institute of Health Guide for the Care and Use of Laboratory Animals(NIH Publications No.80-23,revised 1978)were approved by the Ethics Committee of Mashhad University of Medical Sciences,Iran(IR.MUMS.fm.REC.1397.139).
文摘Background:Zataria multiflora and carvacrol showed various pharmacological prop-erties including anti-inflammatory and anti-oxidant effects.However,up to now no studies have explored its potential benefits in ameliorating sepsis-induced aortic and cardiac injury.Thus,this study aimed to investigate the effects of Z.multiflora and carvacrol on nitric oxide(NO)and oxidative stress indicators in lipopolysaccharide(LPS)-induced aortic and cardiac injury.Methods:Adult male Wistar rats were assigned to:Control,lipopolysaccharide(LPS)(1 mg/kg,intraperitoneal(i.p.)),and Z.multiflora hydro-ethanolic extract(ZME,50–200 mg/kg,oral)-and carvacrol(25–100 mg/kg,oral)-treated groups.LPS was in-jected daily for 14 days.Treatment with ZME and carvacrol started 3 days before LPS administration and treatment continued during LPS administration.At the end of the study,the levels of malondialdehyde(MDA),NO,thiols,and antioxidant enzymes were evaluated.Results:Our findings showed a significant reduction in the levels of superoxide dis-mutase(SOD),catalase(CAT),and thiols in the LPS group,which were restored by ZME and carvacrol.Furthermore,ZME and carvacrol decreased MDA and NO in car-diac and aortic tissues of LPS-injected rats.Conclusions:The results suggest protective effects of ZME and carvacrol on LPS-induced cardiovascular injury via improved redox hemostasis and attenuated NO pro-duction.However,additional studies are needed to elucidate the effects of ZME and its constituents on inflammatory responses mediated by LPS.
文摘BACKGROUND Cardiac syndrome X(CSX)is characterized by persistent angina with normal coronary arteries.Several pathophysiologic mechanisms have been introduced,particularly Helicobacter pylori(H.pylori)infection.AIM To investigate the association between H.pylori infection and CSX.METHODS All studies related to H.pylori infection and CSX were evaluated by comprehensive searches of global databases such as ISI Web of Knowledge,PubMed,Scopus,EMBASE,and Google scholar.Statistical analyses of selected articles were evaluated based on the summary odds ratio(OR).Finally,heterogeneity and publication bias were estimated using the I2 statistic and Cochrane Q-test as well as Begg’s and Egger’s tests.RESULTS A total of 11 studies met our inclusion criteria and 1435 patients(63%female,and 37%male)were reviewed.A significant association was observed between female patients and this syndrome(P=0.02).Our results showed a positive association between infection with this pathogen and presence of CSX(OR:5.65;95%confidence interval[CI]:4.17-7.64;I2:82.20).However,no significant association was observed with cagA-positive H. pylori strains and this syndrome (OR: 0.97;0.56-1.70 with 95%CI). Given the heterogeneity and publication bias, the resultsneed to confirmed by further prospective investigation.CONCLUSIONBased on our results, H. pylori infection is associated with an increased risk ofCSX. This bacterium appears to play a major role in the pathogenesis of CXS byinducing persistent inflammation.
基金Supported by Isfahan University of Medical Sciences(No.340081)。
文摘Objective:To investigate the effect and safety of phytosomal curcumin supplementation on patients with migraine.Methods:In this randomized,double-blind and placebo-controlled trial,70 patients suffered from migraine without aura were randomized into 2 groups to receive 250 mg/d of phytosomal curcumin(intervention group)or maltodextrin(placebo group)for 8 weeks,35 cases per group.All patients in both groups received their standard treatment and common medications.The severity,duration,frequency of headaches,quality of life(QoL),mental status,headache impact,and sleep quality of patients were assessed before and after treatment.Adverse effects were also assessed.Results:Sixty-five patients completed the trial(33 in the intervention group and 32 in the placebo group).Phytosomal curcumin supplementation significantly reduced severity,duration and frequency of migraine attacks,stress score,and headache impact,and improved QoL and sleep quality of patients in the intervention group,compared with the placebo group(P<0.05 or P<0.01).However,it had no significant effect on depression and anxiety scores in the intervention group,compared with the placebo group(P>0.05).No adverse effects had been reported in response to the intervention.Conclusion:Phytosomal curcumin as a safe supplement had a beneficial effect on migraine symptoms,stress level,as well as the sleep quality and QoL in patients with migraine.(Trial registration No.IRCT20201129049534N2)
