Scope: Accumulation of glycolytic metabolite methylglyoxal (MG) in diabetic kidney is thought to contribute to the pathogenesis of nephropathy, either as a direct toxin or as a precursor for advanced glycation end products (AGEs). Using (+)-catechin (CE), a novel MG trapper, we investigated whether MG trapping is sufficient to prevent the progression of diabetic nephropathy in type 2 diabetic mice.
Methods and results: CE markedly trapped exogenous MG in a time- and dose-dependent manner and formed mono-MG-CE and di-MG-CE adducts, which were characterized by HPLC-ESI-Q-TOFMS. In vivo, CE administration for 16 wk significantly ameliorated renal dysfunction in type 2 diabetic db/db mice, partially due to MG trapping, which in turn inhibited AGEs formation and lowered proinflammatory cytokines, including tumor necrosis factor α and IL-1β. Similarly, the MG trapping and cellular signaling inhibition effects of CE were observed in human endothelium-derived cells under high glucose conditions.
Conclusion: CE might ameliorate renal dysfunction in diabetic mice as consequences of inhibiting AGEs formation and cutting off inflammatory pathway via MG trapping. Thus, CE may be a potential natural product as an MG scavenger against diabetes-related complications.
Keywords: (+)-Catechin; Diabetic nephropathy; Inflammation; Methylglyoxal; db/db mice.
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