Chronic renal failure rats are highly sensitive to aristolochic acids, which are nephrotoxic and carcinogenic agents.
Aristolochic acid (AA), a component of some Chinese herbal medicines, may cause Chinese Herbs Nephropathy (CHN) and multi-systemic tumors by the formation of AA-DNA adducts. In this study, we established an animal model to further characterize the mechanisms of AA-induced diseases. Our results indicated that AA significantly inhibited rat growth in terms of weight gain. By measuring the serum creatinine levels, AA resulted in considerable damage to the rat renal system, not only for those in which chronic renal failure (CRF) was induced but also for normal healthy rats. Mutation-specific polymerase chain reaction (PCR) and XbaI restriction fragment length polymorphism (RFLP) revealed the CAA-->CTA transversion mutation at codon 61 of the H-ras proto-oncogene from the stomach tissues of CRF rats fed with AA, but not from other tissues of rats in the same experimental group. In addition, no such mutations were found in the tissues of CRF rats without AA treatment or healthy rats fed with AA. Our results strongly demonstrated that AA was in fact nephrotoxic and carcinogenic, especially to those CRF rats.
Cheng
Chen-Li
CL
Division of Urology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
Chen
Kuo-Jung
KJ
Shih
Po-Hung
PH
Lu
Lieng-Yi
LY
Hung
Chia-Fang
CF
Lin
Wen-Ching
WC
Yesong Gu
Jason
J
D000818:Animals; D034341:Aristolochic Acids / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D018736:DNA Adducts / Q000032:analysis; D011905:Genes, ras; D007668:Kidney / Q000187:drug effects*; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000503:physiopathology*; D009369:Neoplasms / Q000139:chemically induced*; D017354:Point Mutation; D051381:Rats; D017208:Rats, Wistar
D034341:Aristolochic Acids; D018736:DNA Adducts; C000228:aristolochic acid I; D003404:Creatinine