Chronic administration of genistein improves aortic reactivity of streptozotocin-diabetic rats: mode of action.
Diabetes mellitus is associated with major cardiovascular risk factors which are responsible for excess morbidity and mortality. Soy isoflavones like genistein are beneficial for correcting the hyperglycemia and preventing some diabetic complications. Thus, the effect of chronic administration of genistein was studied on aortic reactivity of streptozotocin (STZ)-diabetic rats. Male diabetic rats received genistein 1 mg/kg/day (i.p.) for 4 weeks 3 days after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation responses to acetylcholine (ACh) and isosorbide dinitrate (ISD) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to KCL and PE was significantly lower in genistein-treated diabetic rats relative to untreated diabetic ones. Endothelium removal abolished the significant difference between genistein-treated and untreated diabetic groups regarding contractile response to KCl and PE. Meanwhile, endothelium-dependent relaxation to ACh was significantly higher in genistein-treated diabetic rats as compared to diabetic ones. Pretreatment of rings with N(omega)-L-arginine methyl ester (L-NAME) and indomethacin (INDO) significantly attenuated the observed responses. Meanwhile, one-month diabetes resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity in aortic tissue and genistein treatment attenuated the increased MDA content and reduced activity of SOD. Therefore, chronic treatment of diabetic rats with genistein could prevent the abnormal functional changes in vascular reactivity in diabetic rats through nitric oxide- and prostaglandin-dependent pathways and via attenuating oxidative stress in the wall of aortic tissue.
Baluchnejadmojarad
Tourandokht
T
Department of Physiology, School of Medicine, Hemmat Expressway, Iran University of Medical Sciences, PO Box 14155-6183, Tehran, Iran. tmojarad@yahoo.com
Roghani
Mehrdad
M
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D048789:Phytoestrogens / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D004791:Enzyme Inhibitors; D048789:Phytoestrogens; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D019833:Genistein; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester