Beneficial effect of genistein on lowering blood pressure and kidney toxicity in fructose-fed hypertensive rats.

The study evaluates the effects of genistein on blood pressure (BP) and ultrastructural changes in kidney of fructose-fed hypertensive rats. Male Wistar rats were fed a diet containing 60 % starch or 60 % fructose as the source of carbohydrate. After 15 d, rats in each dietary group were divided into two groups and were treated with either genistein (1 mg/kg per d) in dimethylsulfoxide (DMSO) or 30 % DMSO alone. BP, pressor mechanisms, protein kinase C-βII (PKC-βII) expression, endothelial NO synthase (eNOS) expression and renal ultrastructural changes were evaluated after 60 d. Fructose-fed rats displayed significant elevation in BP and heart rate. Significant increase in plasma angiotensin-converting enzyme (ACE) activity, alterations in renal lipid profile, nitrite and kallikrein activity, enhanced expression of membrane-associated PKC-βII and decreased expression of eNOS were observed in them. Histology and electron microscopic studies showed structural changes in the kidney. Genistein administration lowered BP, restored ACE, PKC-βII and eNOS expression and preserved renal ultrastructural integrity. These findings demonstrate that genistein has effects on eNOS activity in renal cells, leading to eNOS activation and NO synthesis. These effects could have been mediated by activation of PKC-βII. The observed benefits of genistein make it a promising candidate for therapy of diabetic kidney disease.