مقایسه اثرات کلوفیبرات و آنالوگ جدید سیلیکون دار بر روی هپاتوسیتهای ایزوله موش صحرایی

Title

Comparative effects of clofibrate and its novel siliconized analogue in isolated rat hepatocytes

English Abstract

Peroxisome proliferator ligands have been found to have hepatoprotective effect against hepatotoxicants induced injuries. The present investigation aimed to study and compare the effects of clofibrate and its newly synthesized analogue, silafibrate on freshly isolated rat hepatocytes. A siliconized analogue of clofibrate was synthesized, whereby the chlorine atom in the phenoxy ring was replaced by trimethylsily and ethyl2-methyl-2- (4-(trimethylsilyl)phenoxy)propionate was prepared. FeIII:8HQ complex elevated ROS formation in hepatocytes. Application of clofibrate at concentrations of 200 ?M rapidly protected hepatocytes against FeIII:8HQ induced oxidative stress in freshly isolated cells, while silafibrate of 200 ?M had better protective effect. Levels of reactive oxygen species (ROS) were measured with the fluorescent probes 2?,7?- dichlorofluorescein diacetate (DCFHDA). Clofibrate at 200, 400 ?M concentrations reduced reactive oxygen species formation. Treatment of the hepatocytes with silafibrate caused a significant decrease in ROS formation in comparison with clofibrate. ??m happened just before cell death and seems to involve the mitochondrial permeability transition pore (MPTP).Consistent with this, fibrates increased hepatic mitochondrial membrane potential (??m). Mitochondrial membrane potential was measured by using Rhodamine 123 fluorescence. Treatment of the hepatocytes with silafibrate led to significant increase in mitochondrial membrane potential (??m) in comparison with clofibrate. These results suggest that fibrates have hepatoprotective effect against oxidative stress. Silafibrate, the novel analogue, has better effect in protection against oxidative stress in comparison with clofibrate.

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