Low-molecular-weight chitosan scavenges methylglyoxal and N(ε)-(carboxyethyl)lysine, the major factors contributing to the pathogenesis of nephropathy

Methylglyoxal (MG) can cause protein glycation, resulting in cell damage and dysfunction. Accumulation of MG and its downstream metabolite N(ε)-(carboxyethyl)lysine (CEL) has been identified in several variations of nephropathy, including diabetic, hypertensive, and gentamicin-induced nephropathies. In this study, we investigated the effects of low-molecular-weight chitosan (lmw-chitosan) on MG-induced carbonyl stress in aristolochic acid-induced nephropathy. We used a buffer to investigate whether MG could be scavenged by lmw-chitosan in vitro. In addition, we also used a mouse model of aristolochic acid-induced nephropathy, which exhibits 12-fold greater accumulation of MG in the kidneys than that found in control animals, to examine whether lmw-chitosan could decrease MG levels in vivo. Examination of the binding of lmw-chitosan with MG in vitro demonstrated that the concentration of lmw-chitosan necessary to achieve 50% inhibition was 4.60 µg mL(−1). Treatment with lmw-chitosan (500 mg kg(−1) day(−1) orally) for 14 days significantly decreased renal MG accumulation from 212.86 ± 24.34 to 86.15 ± 33.79 µg g(−1) protein (p < 0.05) and CEL levels from 4.60 ± 0.27 to 2.84 ± 0.28 µmol µg(−1) protein (p < 0.05) in the aristolochic acid-induced nephropathy model. These data suggest that lmw-chitosan might represent a novel treatment modality for MG-related diseases such as nephropathy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1106-4) contains supplementary material, which is available to authorized users.