Vitamin C attenuates the toxic effect of aristolochic acid on renal tubular cells via decreasing oxidative stress-mediated cell death pathways

Abstract

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 AA-induced cytotoxicity is associated with increases in oxidative stress and caspase-3 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 caspase-dependent and-independent pathways. It is desirable to identify means of inhibiting AA-induced renal damage; therefore, the present study applied an anti-oxidative nutrient, vitamin C, to test whether it can be employed to reduce AA-induced cell cytotoxicity. The results showed that vitamin C decreased AA-induced H2O2 levels, caspase-3 activity and cytotoxicity in renal tubular cells. In conclusion, the present study was the first to demonstrate that AA-induced increases of the H2O2 ratio resulted in renal tubular cell death via caspase-dependent and independent pathways, and that vitamin C can decrease AA-induced increases in H2O2 levels and caspase-3 activity to attenuate AA-induced cell cytotoxicity.