College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon, 305-764, Republic of Korea.
Arch Pharm Res. 2014 Oct;37(10):1345-53. doi: 10.1007/s12272-013-0267-3. Epub 2013 Nov 20.
Diabetes mellitus and its complications have been attributed in part to oxidative stress, against which antioxidant enzymes constitute a major protective mechanism. The present study was performed to investigate the effects of early stage type 2 diabetes in the absence of obesity and liver damage on hepatic antioxidant enzyme expression and oxidative stress using 9-week-old Goto-Kakizaki (GK) rats. Hepatic total antioxidant capacity determined by total oxygen radical scavenging capacity and lipid peroxidation determined by malondialdehyde in plasma and liver were not significantly different between normal Wistar rats and GK rats. These results indicated that oxidative stress is not evident in these type 2 diabetic rats. Hepatic expression levels of antioxidant enzymes, including superoxide dismutase-1, catalase, glutathione peroxidase and reductase, thioredoxin-1, mu- and pi-class glutathione S-transferase (GST), and the gamma-glutamylcysteine ligase catalytic subunit, were not different between normal rats and GK rats. But, hepatic level and activity of alpha-class GST were decreased and peroxiredoxin-1 level was increased in GK rats, suggesting that upregulation of peroxiredoxin-1 compensates for downregulation of alpha-class GST. These results suggest that alpha-class GST and peroxiredoxin-1 in liver can be altered during the early stages of type 2 diabetes in the absence of obesity and severe oxidative stress.
糖尿病及其并发症部分归因于氧化应激,抗氧化酶是主要的保护机制。本研究旨在研究 9 周龄 Goto-Kakizaki(GK)大鼠在不肥胖和无肝损伤的情况下发生 2 型糖尿病早期对肝抗氧化酶表达和氧化应激的影响。通过总氧自由基清除能力测定的肝总抗氧化能力和通过丙二醛测定的血浆和肝脂质过氧化,正常 Wistar 大鼠和 GK 大鼠之间没有显著差异。这些结果表明,这些 2 型糖尿病大鼠没有明显的氧化应激。超氧化物歧化酶-1、过氧化氢酶、谷胱甘肽过氧化物酶和还原酶、硫氧还蛋白-1、mu 和 pi 类谷胱甘肽 S-转移酶(GST)以及γ-谷氨酰半胱氨酸连接酶催化亚基等肝抗氧化酶的表达水平在正常大鼠和 GK 大鼠之间没有差异。但是,GK 大鼠的肝 alpha 类 GST 水平和活性降低,而过氧化物还原酶-1 水平升高,表明过氧化物还原酶-1 的上调补偿了 alpha 类 GST 的下调。这些结果表明,在没有肥胖和严重氧化应激的情况下,2 型糖尿病早期肝中 alpha 类 GST 和过氧化物还原酶-1 可以发生改变。