Genistein protects methylglyoxal-induced oxidative DNA damage and cell injury in human mononuclear cells

Abstract

Methylglyoxal (MG) is a reactive dicarbonyl compound produced mainly from glycolytic intermediates in the cell and often found at high level in the blood from the diabetic patients. Glycation reactions of MG with amino acids can induce oxidative stress and free radical generation, leading to subsequent cytotoxicity and apoptosis. Recently, studies have demonstrated that high level MG may be the main cause of immune dysfunction in diabetic patients. Here, we examined the effects of genistein, an antioxidant isoflavone compound, on MG-induced effects in vitro and in human mononuclear cells. We first monitored DNA strand breakage to examine the effect of 12.5–100 μM genistein on the ROS generation and oxidative DNA damage induced in vitro by a 50 μM MG/lysine glycation reaction (3 h). Our results revealed that genistein concentrations higher than 25 μM decreased the oxidative stress and DNA damage induced by 50 μM MG/lysine. In mononuclear cells, pretreatment with 8–16 μM genistein for 1 h followed by co-incubation with genistein and 50 μM MG for an additional 36 h inhibited MG-induced reactive oxygen species (ROS) generation and apoptosis. Finally, animal model experiments showed that dietary genistein effectively blocks MG-induced apoptosis in mononuclear cells. These results collectively suggest that oxidative stress plays a role in MG-induced cell injury, and that genistein blocks these effects by virtue of its antioxidant properties, consequently preventing cell apoptosis.