The protective role of enalapril on kidney functions in fructose induced metabolic syndrome in rats

Metabolic syndrome is an entity characterized by insülin resistance, hyperinsulinemia, hypertension, dyslipidemia and obesity. In recent years dietary fructose consumption has been predicted as an enviromental factor which causes obesity and anomalies caused by metabolic syndrome. In experimental models of fructose induced metabolic syndrome hypertension, hypertriglyceridemia, hyperinsulinemia and insülin resistance were seen in rats. Traditionally, renin angiotensin system has physiological and pathophysiological effects on renal and cardiovascular system. By activating this system, blood pressure increases via vasoconstriction, renal tubular and glomerular functions change. By blocking this system, blood pressure drops and renal functions are protected in nephropathic patients. Enalapril is an ACE inhibitör. Enalapril and other drugs in this group inhibits the enzyme dipeptidyl carboxypeptidase which hydrolysis angiotensin-I to angiotensin-II. The aim of this study is to determine the potential protective roles on kidney functions, plasma lipid levels and some intracellular pathway markers of enalapril in an experimental model of metabolic syndrome induced by fructose in rats. 28 Wistar albino male rats (8 weeks old) were included in this study and they were divided into 4 equal groups such as group 1 control group (fed with standart rat chow), group 2 fructose group (fed with high fructose diet [60% fructose]), group 3 enalapril group ( fed with standart rat chow and enalapril [10mg/kg/day] applied in drinking water), group 4 fructose and enalapril group (fed with high fructose diet and enalapril applied in drinking water). Rats were sacrificed after 8 weeks. Blood samples were taken for kidney and liver function tests and lipid leves; kidney and liver tissue samples were collected for western blot analysis and histopathologic examination. TGF-β, TNF-α, NF-κB, IL-6, Smad-3 protein expressions were quantified by western blotting. Administration of enalapril on high fructose fed rats showed significant improvement on serum glucose, total cholesterol, LDL, triglyceride, AST, ALT and creatinin levels but had no effect on HDL and BUN parameters. Administration of enalapril on high fructose fed rats caused a decrease on hepatocellular necrosis, sinusoidal dilatation and portal inflammation in liver tissues. In kidney tissues, administration of enalapril had a positive effect on tubular vacuolization, tubular dilatation and interstitial inflammation. Administration of enalapril on high fructose fed rats caused a decrease on TGF-β, IL-6, Smad-3 expressions but had no effect on NF-κB, TNF-α expressions. In conclusion, feeding with high fructose causes aggravative and destructive effects on kidney and liver function tests and histopathology but administration of enalapril showed significant improvement on these parameters. It can be said that blocking RAS may be an important treatment modality in metabolic syndrome. Keywords: Metabolic syndrome, fructose, enalapril, kidney functions