کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2602819 1133799 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Double antioxidant activities of rosiglitazone against high glucose-induced oxidative stress in hepatocyte
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Double antioxidant activities of rosiglitazone against high glucose-induced oxidative stress in hepatocyte
چکیده انگلیسی

Chronic hyperglycemia is the hallmark of diabetes and its complication. High glucose-induced excessive reactive oxygen species (ROS) production has been considered to play an important role in the development of diabetes. However, the influence of high glucose on the liver remains to be clarified. Rosiglitazone (RSG) is a member of thiazolidinediones (TDZs) family, which is the ligand of the of nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPARγ), being used clinically for the treatment of type 2 diabetic patients through their insulin-sensitizing effect. In the present study, we investigated the cytotoxicity of high glucose in QZG hepatocytes and evaluated the protective effect of RSG. The results showed that high glucose significantly reduced cell viability through generation of ROS via activation of PKC, which was inhibited by RSG. On the one hand, RSG notably inhibited the activation of PKC induced by high glucose independent of PPARγ, leading to the decrease of ROS generation. On the other hand, RSG notably increased the expression of key antioxidant transcription factor Nrf2 and antioxidant enzyme HO-1 in a PPARγ-dependent manner, leading to the elimination of excessive ROS. In addition, RSG also inhibited the decrease of COX-2 expression induced by high glucose through activating PPARγ. Furthermore, the activation of Akt and MAPKs was involved in the effect of RSG on Nrf2, HO-1 and COX-2. In summary, our study supports the hypothesis that RSG protect hepatocytes from high glucose-induced toxicity through PPARγ-dependent and PPARγ-independent pathways.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 25, Issue 4, June 2011, Pages 839–847
نویسندگان
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