Presently, several health institutions, including the U.S. Food and Drug Administration (USFDA), have
recently published safety information related to the presence of AAs in plant materials to prevent further cases of intoxication. Interestingly and fortunately, only 2–3% of persons treated with weight-reducing pillscontaining aristolochic acid are known to have suffered from renal injury in Belgium (Arlt et al. 2002). Furthermore, in Germany, aristolochic acid has been used by thousands of patients as an immunomodulatory agent for 25 years without any reports of chronic interstitial nephritis (De Broe 1999). The genetic heterogeneity of aristolochic acid metabolism and the individual
or racial susceptibility should not be ignored. However, studies related to the effects of aristolochic
acid use are limited. Different from other drugs, once patients take herbs
containing AAs, their renal function will be impaired even if they cease their administration and eventually these patients will develop permanent chronic renal
failure regardless if the onset feature was chronic or acute. Our results demonstrated that AAI-induces DNA damage and cell cycle arrest in the G2/M phase through
p53-independent pathway in LLC-PK1 cells, prior to cellular apoptosis or necrosis. This study of the molecular mechanism of AAI-induced toxicity in LLC-PK1
cells might explain paucicellular interstitial fibrosis and limited tubular regeneration in the clinical presentation of AAI-associated nephrotoxicity.