Genistein protects methylglyoxal-induced oxidative DNA damage and cell injury in human mononuclear cells.
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 microM genistein on the ROS generation and oxidative DNA damage induced in vitro by a 50 microM MG/lysine glycation reaction (3h). Our results revealed that genistein concentrations higher than 25 microM decreased the oxidative stress and DNA damage induced by 50 microM MG/lysine. In mononuclear cells, pretreatment with 8-16 microM genistein for 1h followed by co-incubation with genistein and 50 microM 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.
Wu
Hsin-Jung
HJ
Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, 200, Chung Pei Road, Chung Li 32023, Taiwan, ROC.
Chan
Wen-Hsiung
WH
D000328:Adult; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004338:Drug Combinations; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011765:Pyruvaldehyde / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D016587:Antimutagenic Agents; D000975:Antioxidants; D004338:Drug Combinations; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D011765:Pyruvaldehyde; D019833:Genistein; C022616:thiazolyl blue