Pioglitazone retrieves hepatic antioxidant DNA repair in a mice model of high fat diet.
Pioglitazone retrieves hepatic antioxidant DNA repair in a mice model of high fat diet.
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DOI：
10.1186/1471-2199-9-82
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发表时间：
2008-09-26
影响因子：
--
通讯作者：
Shin SJ
中科院分区：
文献类型：
--
作者：
Hsiao PJ;Hsieh TJ;Kuo KK;Hung WW;Tsai KB;Yang CH;Yu ML;Shin SJ
据报道，吡格列酮在人体研究中可改善肝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，我们在高脂饮食模型中测定了氧化DNA损伤和修复活性。雄性C57BL/6小鼠分别饲喂脂肪含量为30%的日粮、吡格列酮100 mg/kg/d的日粮和以鼠粮为对照的日粮，为期8周。丙二醛浓度表示组织氧化应激。免疫组化8-oxoG染色检测DNA氧化损伤。采用超氧化物歧化酶（Sod1, Sod2）和DNA糖基化酶（Ogg1, MutY）的实时PCR检测酶促抗氧化防御。免疫组化染色和western blot检测OGG1表达的DNA氧化修复。我们的研究结果表明，肝脏脂肪变性是由高脂肪饮食引起的，并通过添加吡格列酮得到改善。高脂饮食组丙二醛浓度和8-oxoG染色明显增加，吡格列酮则减弱。抗氧化防御机制的基因表达：高脂饮食组Sod1、Sod2、Ogg1和MutY显著降低，吡格列酮联合给药逆转。吡格列酮对高脂饮食中肝脏氧化性DNA损伤的减轻可能是通过上调抗氧化防御机制和氧化性DNA修复活性介导的。氧化损伤的减少可以解释吡格列酮治疗非酒精性脂肪肝患者的临床益处。
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. 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. 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.
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影响因子：
5.1
作者：
Caldwell, Stephen H;Chang, Charissa Y;Krugner-Higby, Lisa
通讯作者：
Krugner-Higby, Lisa
影响因子：
7.4
作者：
Erker, Laura;Schubert, Ralf;Wynshaw-Boris, Anthony
通讯作者：
Wynshaw-Boris, Anthony
影响因子：
12.6
作者：
Lutchman, Glen;Promrat, Kittichai;Hoofnagle, Jay H.
通讯作者：
Hoofnagle, Jay H.
影响因子：
2.9
作者：
Djuric, Z;Lewis, SM;Hart, RW
通讯作者：
Hart, RW
影响因子：
64.8
作者：
Houstis, N;Rosen, ED;Lander, ES
通讯作者：
Lander, ES