The effect of calcium load and the calcium channel blocker verapamil on gentamicin nephrotoxicity in rats

Gentamicin (GM) is used against serious and life-threatening Gram negative infections. However its use is limited by the occurrence of nephrotoxicity. Reports on the interaction between GM nephrotoxicity and calcium (Ca²⁺) or Ca blockers are conflicting. Therefore, in the present work we assessed the effect of treatment of rats with graded doses of calcium carbonate, CaCO₃ (0.25, 0.5 or 1.0 g/kg) orally, or the Ca²⁺ channel blocker verapamil (1.75, 3.5 or 7.0 mg/ kg) intramuscularly (i.m.), on the nephrotoxicity induced by concomitant i.m. treatment with GM (80 mg /kg/day for 6 days). Nephrotoxicity was evaluated histopathologically by light microscopy and biochemically by measuring the concentrations of urea and creatinine in plasma, reduced glutathione (GSH), lipid peroxidation and superoxide dismutase (SOD) activity in kidney cortex. The results indicated that the administration of CaCO₃ produced a dose-dependent amelioration in the biochemical indices of nephrotoxicity in plasma and renal cortex, which was significant at the two higher doses used. The histological picture of the renal proximal tubules followed a similar pattern. Treatment with verapamil induced a dose-dependent potentiation in the biochemical parameters of nephrotoxicity that was significant only at the highest dose used (7 mg/kg). This dose also exacerbated the GM-induced histological necrosis. The above interactions may be clinically relevant in patients treated concurrently with these agents.