Aristolochic acid-induced accumulation of methylglyoxal and N-epsilon-(carboxymethyl)lysine: An important and novel pathway in the pathogenic mechanism for aristolochic acid nephropathy

作者：Li Yi Chieh; Tsai Shin Han; Chen Shih Ming; Chang Ya Min; Huang Tzu Chuan; Huang Yu Ping; Chang Chen Tien; Lee Jen Ai^*

来源：Biochemical and Biophysical Research Communications, 2012, 423(4): 832-837.

DOI：10.1016/j.bbrc.2012.06.049

• Aristolochic acid
• Aristolochic acid nephropathy
• Methylglyoxal
• Advanced glycation end products
• N-epsilon-(carboxymethyl)lysine
• Glutathione

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%26lt;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 %26lt;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 %26lt;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 %26lt;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.

• 出版日期2012-7-13