(+)-Catechin ameliorates diabetic nephropathy by trapping methylglyoxal in type 2 diabetic mice.

Abstract

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.

• Authors: Dina Zhu, Lei Wang, Qile Zhou, Shijun Yan, Zhi Li, Jun Sheng, Wensheng Zhang
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 58 Issue 12 Pg. 2249-60 (Dec 2014) ISSN: 1613-4133 [Electronic] Germany
• PMID: 25243815 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Glycation End Products, Advanced
• Interleukin-1beta
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha
• Pyruvaldehyde
• Catechin

Topics

• Animals
• Catechin (pharmacology)
• Cell Line
• Diabetes Mellitus, Experimental (drug therapy)
• Diabetic Nephropathies (drug therapy)
• Disease Progression
• Down-Regulation
• Glycation End Products, Advanced (metabolism)
• Humans
• Interleukin-1beta (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Phosphorylation
• Pyruvaldehyde (metabolism)
• Transcription Factor RelA (genetics, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)