Aristolochic acid is responsive for aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN), which has attracted international attention. Oxidation and reduction is an essential metabolic process for AAI, a major toxic component of AA, rapid clearance in different species. However, which enzyme participates in AAI metabolism in vivo and whether this metabolic process contributes to AAI nephrotoxicity are unclear.Previous results of Shanghai Institute of Materia Medica(SIMM) showed that hepatic CYP1A participated in AAI oxidation, decreased the levels of AAI in mouse blood and kidney, and attenuated AAI-induced nephrotoxicity. These results has been published in Kidney Int (2008, 73:1231-1239).
Kidney is not only an organ with the strongest reductive capability to AAI but also the target organ of AAI-induced toxicity. So researchers from SIMM further explored which enzyme participates in renal AAI reduction and the effects of this metabolic process on AAI-induced nephrotoxicity. Results showed that NAD(P)H: quinone oxidoreductase 1 (NQO1) was mainly located in proximal renal tubular epithelial cells, which were consistent with the location of renal lesions induced by AAI. Pretreatment of mice with dicoumarol or phenidone, two inhibitors of NQO1, significantly suppressed renal AAI reduction and slowed AAI serum clearance. The levels of AAI in the blood and kidney of dicoumarol-pretreated mice markedly increased while the nephrotoxicity induced by AAI attenuated, indicating that NQO1 participates in renal AAI reduction and may thus contribute to AAI-induced nephrotoxicity. These results has been published in Toxicol Sci (2011 May 24. [Epub ahead of print]). The findings provide new basis for the further mechanism study of AAI-induced nephrotoxicity, new clues for the prevention of AAN, and new ideas for safety study of herbs. 
Full text:http://www.ncbi.nlm.nih.gov/pubmed/21613233