Advances in Pharmacology & Clinical Trials (APCT)

ISSN: 2474-9214

Research Article

Adverse Effects of Ezapril in Rats

Authors: Alsadek HB*, Gamal SS, El-Latif SA and Adly M

DOI: 10.23880/apct-16000165

Abstract

The present study was conducted to throw light on the adverse effect of Ezapril and the protective effect of vit. E and to show the result of the combination between Ezapril and Vit.E on nephrotoxicity and hepatotoxicity induced by Ezapril in rats. Experimental design: After one week of acclimatization, eighty albino rats randomly allocated into 4 equal groups, each of 20 rats. First group (control): rats werte in this group not medicated and served as a control and received normal saline. Second group (Ezapril): rats in this group received oral doses of Ezapril (0.36 mg/kg, P.O. once daily) for successive 21 days. Third group (Vit E): rats in this group received oral doses of Vit.E (1mg/kg, P.O. once daily) for successive21 days as standard anti oxidant. Fourth group (Vit.E +E): rats in this group received acombination of Vit.E (1mg /kg, P.O. once daily) with Ezapril (0.36 mg/kg, P.O. once daily for successive 21 days. At the end of the experiment, all rats were sacrificed, liver and kidney samples were taken and blood was taken and centrifuged to gain serum for liver parameters, kidney parameters and antioxidant enzymes investigations. The result was summarized as follow: 1.Effect of Ezapril, Vit.E and their combination on liver parameters (ALT, AST, ALP, total proteins and serum albumin). Oral administration of Ezapril (0.36 mg/kg, P.O. once daily for successive 21 days ) and administration of Vit.E (1mg /kg, P.O. once daily for successive 21 days showed non significant change in ALT, AST, ALP,Serum albumin but serum proteins showed asignificant decrease. 2. Effect of Ezapril, Vit.E and their combination on kidney parameters (urea and creatinine ). Oral administration of Ezapril (0.36 mg/kg, P.O. once daily for successive 21 days) showed asignificant increase in creatinine and urea level compared with control group. Administration of Vit.E (1mg/kg, P.O. once daily for successive 21 days showed a decrease in creatinine and urea compared with Ezapril group. 3. Effect of Ezapril and Vit.E on antioxidant enzyme activities. Oral administration of Ezapril (0.36 mg/kg, P.O. once daily for successive 21 days) produced asignificant decrease in CAT, SOD and GPX activity compared with control group. Administration of Vit.E (1mg/kg, P.O. once daily for successive 21 days showed a significant increase in CAT, SOD and GPX activity compared with Ezapril group. b) Lipid perioxidation (MDA) Oral Oral administration of Ezapril (0.36 mg/kg, P.O. once daily for successive 21 days) produced asignificant increase in MDA activity compared with control group. Administration of Vit.E (1mg/kg, P.O. once daily for successive 21 days showed a significant decrease in MDA activity compared with Ezapril group. 5. Histopathological findings Regarding to the liver, oral administration of Ezapril Ezapril (0.36 mg/kg, P.O. once daily for successive 21 days ) produced hydropic degeneration in amoderate number of hepatocytes, in the second week,showed degenerative changes in amoderate number of hepatocytes and in third week, showed apparently normal hepatocytes. Connecting to the kidney, Oral Oral administration of Ezapril (0.36 mg/kg, P.O. once daily for successive 21 days) in the first week, showed congestion of the glomerular tufts and mild degenerative changes in the proximal and distal convoluted tubular epithelium and cloudy swelling. In the second week, cystic dilatation of renal tubules and focal interstitial round cell aggregation. In the third week, there was interstitial nephritis. Administration of Vit.E (1mg/kg, P.O. once daily for successive 21 days) and its combination with Ezapril (0.36 mg/kg, P.O. once daily for successive 21 days) on liver showed Most of the hepatocytes were apparently normal a few cells showed degenerative changes mainly cloudy swelling in the first week. As regarded to the kidney, Mild to moderate congestion of renal blood vessles with perivascular edema could be detected cystic dilatation of a moderate number of renal tubules, particularly in the medulla with atrophy of the lining epithelium was observed in the first week.

Keywords: Ezapril; Vitamin E; Antioxidant Activity; Histopathology

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