Effects of chlorpromazine and verapamil on nephrotoxicity of cadmium in rats / 中国药理学与毒理学杂志

ABSTRACT

AIM To study whether chlorpromazine(CPZ) and verapamil (Ver) have protective effects on the nephrotoxicity of cadmium (Cd). METHODS Thirtytwo Wistar rats were divided randomly into four groups.Each agent was injected 5 times per week for 6 weeks.The rats in Cd-treated group were sc injected with CdCl2 7μmol·kg-1. The rats of CPZ- and Ver- pretreated group were ip injected with CPZ 5 mg· kg- 1, Ver 4 mg· kg- 1,respectively, 1 h later sc injected with CdCl2 7 μ mol·kg- 1. The control group was sc injected with saline 2 mL·kg-1 at corresponding time. Twenty-four hours after the last injection, the 24-h urine samples were collected. The renal cortex was also excised. Lactate dehydrogenase (LDH) activity, protein and Cd concentration in urine were determined.The activities of protein kinase C (PKC), Na + -K + -ATPase, Ca2 + -ATPase and Cd concentration of renal cortex were also measured. RESULTS Cd concentrations of renal cortex and urine in rats from Cd-treated group were significantly higher than those of control group.Cd concentrations in urine of rats from CPZ- and Ver-pretreated groups were significantly lower than those of Cd-treated group, but there was no significant change in renal cortex. As compared with control group, LDH activity, protein content in urine and the activities of PKC, Na+ -K+ -ATPase and Ca2+ -ATPase in the rats of Cd-treated group increased significantly. LDH activity, protein content in urine and activities of PKC,Na+ -K+ -ATPase and Ca2+ -ATPase in rats of CPZ- and Ver-pretreated groups were significantly lower than those of Cd-treated group. CONCLUSIONCd could activate the activities of PKC,Na+-K+-ATPase and Ca2+-ATPase. Moreover, pretreatment of CPZ and Ver could reduce nephrotoxicity of Cd.