Oxidative Stress and Liver Injury in Hyperhomocysteinemia

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases and often seen in patients with liver diseases. Studies demonstrate that oxidative stress is one of the causes of homocysteine (Hcy) induced adverse effects in physiology. Folic acid is commonly used for reducing plasma Hcy levels. We have reported that HHcy caused lipid accumulation in rat liver by increasing cholesterol biosynthesis. However, the underlying mechanism of liver injury in HHcy is unknown. In this study, we investigated the effect of HHcy and folic acid on oxidative status in livers of HHcy rats and examined how the oxidative stress translated into liver injury. Our results showed that there was a markedly increase in aminotransferase activities suggesting liver injury in HHcy rats. Oxidative stress markers such as oxidized glutathione and lipid peroxide content were markedly elevated in livers of HHcy rats. The increased oxidative stress was due to the elevated formation of superoxide and peroxynitrite. Folic acid significantly reduced the serum Hcy level in HHcy rats and effectively restored the oxidative status of HHcy comparable to that of the control. These results suggest that Hcy‐induced oxidative stress may contribute to liver injury in HHcy. Folic acid can offer a hepatoprotective effect through lowering blood Hcy levels and reducing the oxidative stress. (Supported by HSF, NSERC, MHRC.)