BACKGROUND Pioglitazone was reported to improve hepatic steatosis and necroinflammation in human studies. To investigate whether the hepato-protective effect of pioglitazone was associated with an improvement of antioxidant defense mechanism, oxidative DNA damage and repair activity were determined in a high fat diet model. Male C57BL/6 mice were respectively fed with a 30% fat diet, the same diet with pioglitazone 100 mg/kg/day, or a chow diet as control for 8 weeks. Tissue oxidative stress was indicated by malondialdehyde concentration. Oxidative DNA damage was detected by immunohistochemical 8-oxoG staining. Enzymatic antioxidant defense was detected by the real-time PCR of superoxide dismutase (Sod1, Sod2) and DNA glycosylase (Ogg1, MutY). Oxidative DNA repair was detected by immunohistochemical staining and western blotting of OGG1 expression. RESULTS Our results show that hepatic steatosis was induced by a high-fat diet and improved by adding pioglitazone. Malondialdehyde concentration and 8-oxoG staining were strongly increased in the high-fat diet group, but attenuated by pioglitazone. Gene expressions of antioxidant defense mechanism: Sod1, Sod2, Ogg1 and MutY significantly decreased in the high-fat diet group but reversed by pioglitazone co-administration. CONCLUSION The attenuation of hepatic oxidative DNA damage by pioglitazone in a high-fat diet may be mediated by up-regulation of the antioxidant defense mechanism and oxidative DNA repair activity. The diminution of oxidative damage may explain the clinical benefit of pioglitazone treatment in patients with non-alcoholic fatty liver disease.

中文翻译：

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吡格列酮在高脂饮食的小鼠模型中恢复肝脏抗氧化剂DNA的修复作用。

背景技术据报道，吡格列酮可改善人体研究中的肝脏脂肪变性和坏死性炎症。为了研究吡格列酮的肝保护作用是否与抗氧化防御机制的改善有关，在高脂饮食模型中确定了氧化DNA损伤和修复活性。雄性C57BL / 6小鼠分别饲喂30％的脂肪饮食，相同的吡格列酮饮食100 mg / kg /天或作为饮食的对照，持续8周。通过丙二醛浓度指示组织氧化应激。通过免疫组织化学8-oxoG染色检测到氧化性DNA损伤。通过实时PCR检测超氧化物歧化酶（Sod1，Sod2）和DNA糖基化酶（Ogg1，MutY）的酶促抗氧化剂防御能力。免疫组化染色和蛋白印迹的OGG1表达检测到氧化DNA修复。结果我们的结果表明，高脂饮食可诱发肝脂肪变性，加入吡格列酮可改善肝脂肪变性。高脂饮食组丙二醛浓度和8-oxoG染色强烈增加，但吡格列酮减弱。高脂饮食组抗氧化防御机制的基因表达：Sod1，Sod2，Ogg1和MutY显着降低，但与吡格列酮合用可逆转。结论吡格列酮在高脂饮食中减轻肝脏氧化DNA损伤的作用可能是通过上调抗氧化防御机制和氧化DNA修复活性来实现的。氧化损伤的减少可能解释了吡格列酮治疗非酒精性脂肪肝患者的临床益处。