AIM:To evaluate the impact of metadoxine(MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis(AH).METHODS:This study was an open-label clinical trial,performed at the"Hospital General de M...AIM:To evaluate the impact of metadoxine(MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis(AH).METHODS:This study was an open-label clinical trial,performed at the"Hospital General de México,Dr.Eduardo Liceaga".We randomized 135 patients who met the criteria for severe AH into the following groups:35 patients received prednisone(PDN)40 mg/d,35patients received PDN+MTD 500 mg three times daily,33 patients received pentoxifylline(PTX)400 mg three times daily,and 32 patients received PTX+MTD 500 mg three times daily.The duration of the treatment for all of the groups was 30 d.RESULTS:In the groups treated with the MTD,thesurvival rate was higher at 3 mo(PTX+MTD 59.4%vs PTX 33.3%,P=0.04;PDN+MTD 68.6%vs PDN20%,P=0.0001)and at 6 mo(PTX+MTD 50%vs PTX18.2%,P=0.01;PDN+MTD 48.6%vs PDN 20%,P=0.003)than in the groups not treated with MTD.A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo.The patients receiving MTD maintained greater abstinence than those who did not receive it(74.5%vs 59.4%,P=0.02).CONCLUSION:MTD improves the 3-and 6-mo survival rates in patients with severe AH.Alcohol abstinence is a key factor for survival in these patients.The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX.展开更多
Alcohol consumption causes significant liver damage,including hepatitis,fibrosis,cirrhosis,and even primary liver carcinoma.Metadoxine(MTDX)is considered to be a beneficial treatment for alcoholic liver disease(ALD)be...Alcohol consumption causes significant liver damage,including hepatitis,fibrosis,cirrhosis,and even primary liver carcinoma.Metadoxine(MTDX)is considered to be a beneficial treatment for alcoholic liver disease(ALD)because it accelerates the metabolism and elimination of ethanol.However,the underlying mechanism is not well understood.Here,the rat model of ALD was developed by feeding with 50%ethanol at the dose of 5 g/kg,and samples of serum and liver tissue were collected to test the levels of liver injury and inflammation and evaluate the hepatoprotective function of MTDX in alcohol-induced liver injury.Further investigation on the infiltration of immune cells was performed to understand the potential hepatoprotective mechanism of MTDX in the ALD model.The results showed that MTDX attenuated liver injury,evidenced by decreased levels of alanine transaminase(ALT),aspartate aminotransferase(AST),and alkaline phosphatase(ALP).Meanwhile,the liver proinflammatory environment was improved after MTDX treatment,evidenced by decreased levels of TNF-α,IL-6,and NLRP3 in the liver tissue.Furthermore,inhibited infiltrations of macrophages and neutrophils were observed in MTDX-treated ALD rats compared with the untreated ALD rats.Our results indicated that MTDX played an important role in preventing the progression of ALD,and the underlying mechanisms might be related to its function of attenuating liver inflammation by inhibiting immune cell infiltration.展开更多
Alcohol-induced liver disease is one of the main .epidemic problems nowadays. Metadoxine is apyridoxine-pyrrolidone carboxylate with significant scavenging property. Metadoxine is able to accelerate the elimination of...Alcohol-induced liver disease is one of the main .epidemic problems nowadays. Metadoxine is apyridoxine-pyrrolidone carboxylate with significant scavenging property. Metadoxine is able to accelerate the elimination of alcohol from the blood and tissues, help restore the functional structure of the liver and relieve neuro-psychological disorders associated with alcohol intoxication.The purpose of the study was to assay the pharmacokinetics of domestic metadoxine after repeated doses.展开更多
目的观察美他多辛对酒精性肝病(ALD)大鼠的保护作用及其对血清细胞因子水平的影响。方法将24只雄性Wistar大鼠分为对照组(NC,n=8)、酒精性肝病组(ALD,n=8)和美他多辛治疗组(MT,n=8)。在NC组和ALD组,给予等渗盐水灌胃,给予MT组等渗盐水...目的观察美他多辛对酒精性肝病(ALD)大鼠的保护作用及其对血清细胞因子水平的影响。方法将24只雄性Wistar大鼠分为对照组(NC,n=8)、酒精性肝病组(ALD,n=8)和美他多辛治疗组(MT,n=8)。在NC组和ALD组,给予等渗盐水灌胃,给予MT组等渗盐水和美他多辛(300 mg·kg^(-1)·d^(-1))灌胃。2 w后,继续给予NC组等渗盐水,而在ALD组和MT组,给予50%酒精5 g·kg^(-1)灌胃,1次/h,共3次。在末次灌胃8 h取血,采用ELISA法检测NF-κB、TNF-α、IL-1β、IL-6、IL-8和IL-10;取肝组织,采用RT-PCR法检测NF-κB和炎症因子m RNA水平。两个样本均数的比较采用t检验或近似t检验,多个样本均数的比较采用LSD检验。结果 ALD组血清ALT较NC组显著升高[(100.13±10.64)U/L对(33.37±4.81)U/L,P<0.05],血清AST和GGT水平也显著升高(P值均<0.05);正常组动物血清IL-10、IL-1β、TNF-α、IL-6、IL8和NF-ΚB水平分别为(14.73±2.03)pg/ml、(92.38±12.85)pg/ml、(2.66±0.81)pg/ml、(43.57±10.62)ng/ml、(0.29±0.07)ng/ml和(679.45±36.38)pg/ml,ALD动物分别为(16.19±1.94)pg/ml、(1927±233.69)pg/ml、(16.92±2.38)pg/ml、(127.49±9.33)ng/ml、(2.63±0.22)ng/ml和(1247.35±146.05)pg/ml,而美他多辛处理组则分别为(36.81±4.53)pg/ml、(304.13±34.79)pg/ml、(8.83±1.01)pg/ml、(81.98±8.02)ng/ml、(1.45±0.22)ng/ml和(814.84±82.40)pg/ml,提示ALD组血清TNF-α、IL-1β、IL-6和IL-8水平显著高于NC组(P值均<0.05),MT组血清TNF-α、IL-1β、IL6和IL-8水平显著低于ALD组(P值均<0.05),IL-10水平显著高于ALD组(P<0.05);ALD组肝组织TNF-α、IL-1β、IL-6和IL-8 m RNA水平显著高于NC组(P值均<0.05),MT组TNF-α、IL-1β、IL-6和IL-8 m RNA水平显著低于,而IL-10 m RNA水平显著高于ALD组(P<0.05)。结论美他多辛对酒精性肝病大鼠的肝损伤有显著的保护作用,其机制可能是抑制了与NF-κB相关的炎症反应,进而抑制了TNF-α、IL-1β、IL6和IL-8等促炎因子水平,升高了抗炎因子IL-10水平有关。展开更多
基金Supported by Fatima Higuera-de la Tijera through the"Angeles Espinosa Yglesias 2010"stimulus granted by the FUNSALUD AC,AMPARO Foundation and FUNDHEPA AC,Mexico
文摘AIM:To evaluate the impact of metadoxine(MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis(AH).METHODS:This study was an open-label clinical trial,performed at the"Hospital General de México,Dr.Eduardo Liceaga".We randomized 135 patients who met the criteria for severe AH into the following groups:35 patients received prednisone(PDN)40 mg/d,35patients received PDN+MTD 500 mg three times daily,33 patients received pentoxifylline(PTX)400 mg three times daily,and 32 patients received PTX+MTD 500 mg three times daily.The duration of the treatment for all of the groups was 30 d.RESULTS:In the groups treated with the MTD,thesurvival rate was higher at 3 mo(PTX+MTD 59.4%vs PTX 33.3%,P=0.04;PDN+MTD 68.6%vs PDN20%,P=0.0001)and at 6 mo(PTX+MTD 50%vs PTX18.2%,P=0.01;PDN+MTD 48.6%vs PDN 20%,P=0.003)than in the groups not treated with MTD.A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo.The patients receiving MTD maintained greater abstinence than those who did not receive it(74.5%vs 59.4%,P=0.02).CONCLUSION:MTD improves the 3-and 6-mo survival rates in patients with severe AH.Alcohol abstinence is a key factor for survival in these patients.The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX.
基金Jinan Technology Development Program(Grant No.201907035)。
文摘Alcohol consumption causes significant liver damage,including hepatitis,fibrosis,cirrhosis,and even primary liver carcinoma.Metadoxine(MTDX)is considered to be a beneficial treatment for alcoholic liver disease(ALD)because it accelerates the metabolism and elimination of ethanol.However,the underlying mechanism is not well understood.Here,the rat model of ALD was developed by feeding with 50%ethanol at the dose of 5 g/kg,and samples of serum and liver tissue were collected to test the levels of liver injury and inflammation and evaluate the hepatoprotective function of MTDX in alcohol-induced liver injury.Further investigation on the infiltration of immune cells was performed to understand the potential hepatoprotective mechanism of MTDX in the ALD model.The results showed that MTDX attenuated liver injury,evidenced by decreased levels of alanine transaminase(ALT),aspartate aminotransferase(AST),and alkaline phosphatase(ALP).Meanwhile,the liver proinflammatory environment was improved after MTDX treatment,evidenced by decreased levels of TNF-α,IL-6,and NLRP3 in the liver tissue.Furthermore,inhibited infiltrations of macrophages and neutrophils were observed in MTDX-treated ALD rats compared with the untreated ALD rats.Our results indicated that MTDX played an important role in preventing the progression of ALD,and the underlying mechanisms might be related to its function of attenuating liver inflammation by inhibiting immune cell infiltration.
文摘Alcohol-induced liver disease is one of the main .epidemic problems nowadays. Metadoxine is apyridoxine-pyrrolidone carboxylate with significant scavenging property. Metadoxine is able to accelerate the elimination of alcohol from the blood and tissues, help restore the functional structure of the liver and relieve neuro-psychological disorders associated with alcohol intoxication.The purpose of the study was to assay the pharmacokinetics of domestic metadoxine after repeated doses.
文摘目的观察美他多辛对酒精性肝病(ALD)大鼠的保护作用及其对血清细胞因子水平的影响。方法将24只雄性Wistar大鼠分为对照组(NC,n=8)、酒精性肝病组(ALD,n=8)和美他多辛治疗组(MT,n=8)。在NC组和ALD组,给予等渗盐水灌胃,给予MT组等渗盐水和美他多辛(300 mg·kg^(-1)·d^(-1))灌胃。2 w后,继续给予NC组等渗盐水,而在ALD组和MT组,给予50%酒精5 g·kg^(-1)灌胃,1次/h,共3次。在末次灌胃8 h取血,采用ELISA法检测NF-κB、TNF-α、IL-1β、IL-6、IL-8和IL-10;取肝组织,采用RT-PCR法检测NF-κB和炎症因子m RNA水平。两个样本均数的比较采用t检验或近似t检验,多个样本均数的比较采用LSD检验。结果 ALD组血清ALT较NC组显著升高[(100.13±10.64)U/L对(33.37±4.81)U/L,P<0.05],血清AST和GGT水平也显著升高(P值均<0.05);正常组动物血清IL-10、IL-1β、TNF-α、IL-6、IL8和NF-ΚB水平分别为(14.73±2.03)pg/ml、(92.38±12.85)pg/ml、(2.66±0.81)pg/ml、(43.57±10.62)ng/ml、(0.29±0.07)ng/ml和(679.45±36.38)pg/ml,ALD动物分别为(16.19±1.94)pg/ml、(1927±233.69)pg/ml、(16.92±2.38)pg/ml、(127.49±9.33)ng/ml、(2.63±0.22)ng/ml和(1247.35±146.05)pg/ml,而美他多辛处理组则分别为(36.81±4.53)pg/ml、(304.13±34.79)pg/ml、(8.83±1.01)pg/ml、(81.98±8.02)ng/ml、(1.45±0.22)ng/ml和(814.84±82.40)pg/ml,提示ALD组血清TNF-α、IL-1β、IL-6和IL-8水平显著高于NC组(P值均<0.05),MT组血清TNF-α、IL-1β、IL6和IL-8水平显著低于ALD组(P值均<0.05),IL-10水平显著高于ALD组(P<0.05);ALD组肝组织TNF-α、IL-1β、IL-6和IL-8 m RNA水平显著高于NC组(P值均<0.05),MT组TNF-α、IL-1β、IL-6和IL-8 m RNA水平显著低于,而IL-10 m RNA水平显著高于ALD组(P<0.05)。结论美他多辛对酒精性肝病大鼠的肝损伤有显著的保护作用,其机制可能是抑制了与NF-κB相关的炎症反应,进而抑制了TNF-α、IL-1β、IL6和IL-8等促炎因子水平,升高了抗炎因子IL-10水平有关。
