期刊
TOXICOLOGY IN VITRO
卷 25, 期 4, 页码 839-847出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2011.02.004
关键词
Rosiglitazone; Antioxidant activity; High glucose; ROS; PPAR gamma
类别
资金
- National Natural Science Foundation [30872135]
- Natural Science Foundation of Shaanxi Province [2010JZ004]
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-gamma (PPAR gamma), 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 PPAR gamma, 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 PPAR gamma-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 PPAR gamma. 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 PPAR gamma-dependent and PPAR gamma-independent pathways. (C) 2011 Elsevier Ltd. All rights reserved.
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