Nephroprotective effect of calcium channel blockers against toxicity of lead exposure in mice

Exposure to lead (Pb) can induce kidney damage, which is related to induction of oxidative damage and disturbance of intracellular calcium homeostasis. Pb can readily permeate through dihydropyridine-sensitive L-type calcium channels and accumulate within cells. The objective of this study was to investigate protective effects of calcium channel blockers (CCBs) verapamil and nimodipine on nephrotoxicity induced by Pb acetate in mice. One hundred and twenty male mice were randomly divided into 6 groups: control, Pb, low-dose verapamil, high-dose verapamil, low-dose nimodipine and high-dose nimodipine (n = 20 per group). Pb acetate was injected intraperitoneally (i.p.) at 40 mg/kg body weight/day for 10 days to establish the Pb toxicity model. While control mice received saline, mice of the treated groups simultaneously received i.p. injections of verapamil or nimodipine daily for 10 days. Both verapamil and nimodipine showed protection against Pb-induced kidney injury, including alleviation of renal pathological damage and decreasing the level of Pb in kidney homogenate and extent of apoptosis in nephrocytes. Moreover, verapamil and nimodipine significantly down-regulated levels of blood urea nitrogen and creatinine in the serum. In addition, verapamil and nimodipine administration decreased malondialdehyde content and increased activities of super oxide dismutase activity and glutathione peroxidase in the kidney homogenate. The findings in the present study implicate the therapeutic potential of CCBs for Pb-induced nephrotoxicity, which were at least partly due to the decrease of Pb uptake and inhibition of lipid peroxidation.

► CCBs reduced renal Pb accumulation in mice with Pb-induced kidney damage. ► CCBs alleviated renal pathological damage and nephrocyte apoptosis induced by Pb. ► CCBs inhibited lipid peroxidation induced by Pb. ► CCBs shows the protective effects on Pb-induced nephrotoxicity.