The Effect of Calcium Channel Blocker Verapamil on Gentamicin Nephrotoxicity in Rats

Abstract

Aminoglycoside antibiotics are obligated nephrotoxins and inevitably cause renal failure during prolonged use. Experimental models of gentamicin-induced nephrotoxicity have shown histopathological, ultrastructural and functional alteration with blood urea nitrogen and serum creatinine increase leading to acute renal insufficiency (ARI). The aim of our study was to emphasize effects of verapamil, a calcium channel blocker, on gentamicin-induced ARI in rats. Experiments were done on 50 male Wistar rats (250-300 g) divided in three experimental groups. G-group animals (20 rats) were treated daily with gentamicin in dose of 100 mg/kg during 8 days. GV-group animals (20 rats) were treated daily with verapamil in dose of 3 mg/kg and the same dose of gentamicin as in G-group during 8 days. The control group (10 rats) received 1 ml/day saline intraperitoneally. Histological examinations were done using hematoxylin and eosin, periodic acid Schiff and methenamine silver staining methods. Morphometric parameters included measurement of glomerular area, major and minor axis, perimeter, diameter, roundness, and mean optical density. Biochemical analyses were used to determine concentrations of blood urea, serum creatinine, sodium and potassium. In G-group rats’ glomerular basement membrane was diffusely and unequally thickened with polymorphonuclear neutrophils infiltration, while coagulation-type necrosis and vacuolization of cytoplasm of proximal tubules epithelial cells were observed. In GV-group rats’ glomeruli were slightly enlarged with thickened basement membrane in some segments but without coagulation-type necrosis. Morphometric analyses showed statistically significant differences between the G-group and control group of animals in glomerular size, mean optical density and average roundness (p<0,05). On the other hand, morphometric analyses between GV-group and control group animals did not show statistically significant differences in any of parameters measured. Blood urea and serum creatinine concentration in G-group were significantly elevated in comparison with GV-group (p<0,05) but sodium and potassium levels in G-group were decreased compared to GV-group without statistical significance. Our results show that verapamil modify some of morphological and functional kidney alterations induced by gentamicin.