Post-Graduation Program in Medical Sciences, Medical School, Federal University of Rio Grande do Sul (UFRGS), 90035-903 Porto Alegre, RS, Brazil.
Research Center, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul (UFRGS), 90035-903 Porto Alegre, RS, Brazil.
Oxid Med Cell Longev. 2019 Jun 18;2019:3201873. doi: 10.1155/2019/3201873. eCollection 2019.
In this study, we evaluated the efficacy of simvastatin in the treatment of nonalcoholic steatohepatitis induced by methionine and choline-deficient diet in mice and its possible effect on factors involved in the pathogenesis of the disease including oxidative stress and endoplasmic reticulum stress.
Male C57BL6 mice were fed either a normal diet (control) or a methionine and choline-deficient diet for four weeks and then treated orally with simvastatin (4 mg/kg once a day) for two final weeks. At the end of the experimental period, liver integrity, biochemical analysis, hepatic lipids, histology, DNA damage, biomarkers of oxidative stress, and endoplasmic reticulum stress were assessed.
Simvastatin treatment was able to significantly reduce hepatic damage enzymes and hepatic lipids and lower the degree of hepatocellular ballooning, without showing genotoxic effects. Simvastatin caused significant decreases in lipid peroxidation, with some changes in antioxidant enzymes superoxide dismutase and glutathione peroxidase. Simvastatin activates antioxidant enzymes via Nrf2 and inhibits endoplasmic reticulum stress in the liver.
In summary, the results provide evidence that in mice with experimental nonalcoholic steatohepatitis induced by a methionine and choline-deficient diet, the reduction of liver damage by simvastatin is associated with attenuated oxidative and endoplasmic reticulum stress.
本研究旨在评估辛伐他汀在治疗蛋氨酸和胆碱缺乏饮食诱导的小鼠非酒精性脂肪性肝炎中的疗效及其对疾病发病机制相关因素的可能影响，包括氧化应激和内质网应激。
雄性 C57BL6 小鼠分别喂食正常饮食（对照组）或蛋氨酸和胆碱缺乏饮食 4 周，然后再用辛伐他汀（4mg/kg，每天 1 次）治疗 2 周。在实验期末，评估肝完整性、生化分析、肝脂质、组织学、DNA 损伤、氧化应激生物标志物和内质网应激。
辛伐他汀治疗可显著降低肝损伤酶和肝脂质，降低肝细胞气球样变程度，且无遗传毒性作用。辛伐他汀引起脂质过氧化显著降低，抗氧化酶超氧化物歧化酶和谷胱甘肽过氧化物酶有一些变化。辛伐他汀通过 Nrf2 激活抗氧化酶并抑制肝脏内质网应激。
总之，研究结果表明，在蛋氨酸和胆碱缺乏饮食诱导的实验性非酒精性脂肪性肝炎小鼠中，辛伐他汀降低肝损伤与减轻氧化应激和内质网应激有关。
