Vitamin C attenuates the toxic effect of aristolochic acid on renal tubular cells via decreasing oxidative stress­mediated cell death pathways.

Aristolochic acid (AA) is a component of Chinese medicinal herbs, including asarum and aristolochia and has been used in Traditional Chinese Medicine for a long time. Recent studies found that AA has a cytotoxic effect resulting in nephropathy. These studies indicated that AA­induced cytotoxicity is associated with increases in oxidative stress and caspase­3 activation. The present study further demonstrated that AA mainly elevates the H2O2 ratio, leading to increases in oxidative stress. Furthermore, the results indicated that AA induces cell death can via caspase­dependent and ­independent pathways. It is desirable to identify means of inhibiting AA­induced renal damage; therefore, the present study applied an anti­oxidative nutrient, vitamin C, to test whether it can be employed to reduce AA­induced cell cytotoxicity. The results showed that vitamin C decreased AA­induced H2O2 levels, caspase­3 activity and cytotoxicity in renal tubular cells. In conclusion, the present study was the first to demonstrate that AA­induced increases of the H2O2 ratio resulted in renal tubular cell death via caspase­dependent and ­independent pathways, and that vitamin C can decrease AA­induced increases in H2O2 levels and caspase­3 activity to attenuate AA­induced cell cytotoxicity.