Abstract
Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is a key precursor of the formation of advanced glycation end products (AGEs). MGO and MGO-AGEs were reportedly increased in patients with diabetic dysfunction, including diabetic nephropathy. The activation of glyoxalase-I (GLO-I) increases MGO and MGO-AGE detoxification. MGO-mediated glucotoxicity can also be ameliorated by MGO scavengers such as N-acetylcysteine (NAC), aminoguanidine (AG), and metformin. In this study, we noted that l-cysteine demonstrated protective effects against MGO-induced glucotoxicity in renal mesangial cells. l-cysteine prevented MGO-induced apoptosis and necrosis, together with a reduction of reactive oxygen species (ROS) production in MES13 cells. Interestingly, l-cysteine significantly reduced MGO-AGE formation and also acted as an MGO-AGE crosslink breaker. Furthermore, l-cysteine treatment accelerated MGO catabolism to D-lactate via the upregulation of GLO-I. The reduction of AGE formation and induction of AGE breakdown, following l-cysteine treatment, further supports the potential use of l-cysteine as an alternative for the therapeutic control of MGO-induced renal complications in diabetes, especially against diabetic nephropathy.