Aristolochic acid, found in the Aristolochia species, causes aristolochic acid nephropathy (AAN) and can develop into renal failure. Methylglyoxal (MGO) is a highly cytotoxic compound generated from the metabolic process of glucose or fatty acids. It binds to proteins and forms N-epsilon-(carboxymethyl)lysine (CML), which contributes to aging and diabetes mellitus complications. However, no relevant literature explores the relationship of MGO and CML with AAN. By injecting AA (10 mg/kg BW) into C3H/He mice for 5 consecutive days, we successfully developed an AAN model and observed tubular atrophy with decreased renal function. Creatinine clearance also decreased from 10.32 +/- 0.79 ml/min/kg to 2.19 +/- 0.29 ml/min/kg (p<0.01). The concentration of MGO in kidney homogenates increased 12xcompared to the control group (from 18.23 +/- 8.05 mu g/mg of protein to 231.16 +/- 17.57 mu g/mg of protein, p <0.01), and CML was observed in the renal tubules of the mice by immunohistochemistry. Furthermore, compared to the control group, GSH levels decreased by 0.32 x(from 2.46 +/- 0.41 mu M/mu g of protein to 0.78 +/- 0.15 mu M/mu g of protein, p <0.01), whereas intra-renal antioxidant capacity decreased by 0.54 x(from 6.82 +/- 0.97 U to 3.71 +/- 0.25 U; unit is equivalent to mu M Trolox/mg of protein, p <0.01). In this study, we found that serious kidney damage induced by AA is related to an increase and accumulation of MGO and CML. (C) 2012 Elsevier Inc. All rights reserved.