The Potential Effect Of Resveratrol On Arsenic-induced Oxidative Stress In Rats

The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the past hundreds of years, arsenic has been used as a pesticide, a chemotherapeutic agent. While arsenic trioxide(As2O3) exerts the effect on leukemiafor, particularly acute promyelocytic leukemia(APL). However, there is the hepatotoxicity during the therapy for APL. Currently, the mode of action of arsenic for its disease endpoints is under studying. The oxidative stress, both at home and abroad, has been demonstrated to become a critical issue with the reason of involving in the process of toxicity. A plenty of documents reported that reactive oxygen species(ROS) can be decreased by the antioxidant.Resveratrol(RES), trans-3,5,4’-trihydroxystilbene, is a naturally occurring phytoalexin produced by a wide variety of plants because they are protective agents synthesized by plants in case of microbial attack, excessive ultraviolet exposure and diseases. Besides cardioprotective effects, resveratrol exhibits anticancer properties, as suggested by its ability to suppress proliferation of a wide variety of tumor cells. The effect of RES on liver of rats exposed to arsenic and the apoptosis of hepatocyte in vivo(control rats, rats exposed to arsenic) and vitro(primer hepatocyte from rat, hepatocyte exposed to arsenic or RES) were explored using the cell biological and molecular biological methods. The striking increase in aspartate transaminase, alanine transaminase and lactate dehydrogenase as well as oxidative stress makers, such as ROS level(750.29±81.33 Unites/ml) and malondialdehyde content(4.9±0.67μmol/L) and the significant decrease in superoxide dismutase(7.42±1.14 Unites/ml), gluthione peroxide(215.93±35.19 Unites/L) and catalase activities(3.66±0.32 Unites/ml) in serum of rats exposed to arsenic compared with the control rats were observed, what’s more, the arsenic accumulation in arsenic-treated group was more about 7 times than that in control group; however, pretreatment with RES reversed the oxidative stress and attenuated the liver tissue damage and arsenic accumulation induced by As2O3(p <0.05). To explore the relationship between As2O3- induced oxidative stress and apoptosis as well as the potential mechanism, we used the primary hepatocyte from normal rat using the two-step perfusion method with or without RES during exposure to arsenic. As2O3 induced oxidative stress in hepatocyte and the relative apoptosis genes of hepatocyte, including Fax, Bcl-2, Bax, TNF-α and Caspase-3 were determined. In the present study, oxidative stress induced by As2O3 in hepatocyte was also seen; the activation of Fas/TNF signal transduction were not observed, nevertheless, Bcl-2/Bax as an important the mitochondrial apoptosis pathway was shown the significant increase in comparison with the control group. However, the expression of Caspase-3 gene was not increased with the reason of which the activity of Caspase-3 protein plays a crucial role in the mitochondrial apoptosis, rather than Caspase-3 gene. The activity of Caspase-3 was increased markedly in As2O3-treated group, whereas the present with RES could slow down the 20% increase in the following study. In summary, pretreatment with RES can attenuate As2O3-induced oxidative stress, arsenic accumulation and pathological damage in rats wherever rats or hepatocyte, in addition, arsenic induced hepatocyte apoptosis through the mitochondrial Bcl-2/Bax pathway. These suggest that arsenic as a drug can attenuate the oxidative stress, hepatocyte apoptosis induced the arsenic and arsenic accumulation, thereby decreasing the pathological damage. There were no difference from control when RES alone was treated rats and liver cell in the whole study. However, whether RES is involved in the cell autophagy associated with the apoptosis during exposure to arsenic has yet to be determined and the further study remains to be evaluated.Based on these, we suggest that this study can be favorable to know better the mechanism, the prevention the therapy of arsenic exposure, wherever the APL and arsenic contamination.