Comparative Nephrotoxicity of Aristolochic Acid and Tetrandrine In Vitro and In Vivo

Aristolochic acid (AA) and tetrandrine (TET) are the major bioactive components in Chinese herbs used for weight loss. The nephropathy caused by the 2 Chinese herbs has not been simultaneously investigated. The aim of this study was to examine the potential nephrotoxicity of AA and TET using Madin-Darby canine kidney (MDCK) cells and mice. The results showed that TET was more potent than AA in inhibiting MDCK cell growth via inducing apoptosis, as determined by annexin-V staining, 4', 6'-diamino-2-phenylindole (DAPI) staining, DNA fragmentation, and caspase 3 activity. Mice treated with AA (10 mg/kg) by intraperitoneal administration for 3 months showed nephrotoxicity, elevated blood urea nitrogen, and increased renal tubular injuries. In contrast, mice treated with 50 mg/kg of TET in the same time period had moderate hydropic degeneration of the distal tubules in the kidneys. These results suggest that TET is more cytotoxic than AA in MDCK cells but shows less nephrotoxic than AA in mice.