Protective effects of Chlorpromazine and Verapamil against cadmium-induced kidney damage in vivo.
Overexposure to cadmium (Cd) can induce kidney damage, which was related to the oxidative damage and disturb intracellular Ca2+ homeostasis. Chlorpromazine (CPZ), targeting calmodulin (CaM), and the Ca2+ channel blocker Verapamil (Ver) are involved in intracellular Ca2+ homeostasis processes. The aim of the study was to investigate the kidney damage caused by Cd administrated for 6 weeks and to evaluate the effects of pre-treatment with either chlorpromazine or verapamil on Cd-induced kidney damage. Thirty-two Wistar rats were divided randomly into 4 groups by weight, i.e., control group, Cd-treated group, and CPZ or Ver pre-treated group. The Cd-treated group rats were subcutaneously (s.c.) injected with 7micromol CdCl2/kg body weight/day. The CPZ and Ver pre-treated group rats were intraperitoneally (i.p.) injected with 5mg CPZ/kg body weight/day, 4mg Ver/kg body weight/day, respectively, 1h before the s.c. administration of 7micromol CdCl2/kg body weight/day. The control group rats were injected s.c. with saline at the same time. The volume of injection was 2ml/kg body weight, 5 times per week, for up to 6 weeks. After 6 weeks, Cd concentrations in the renal cortex and urine were significantly higher in Cd-treated group than that in controls. Cd concentrations of the urine in CPZ and Ver pre-treated groups were significantly lower than that in Cd-treated group, but there were no significant changes in the renal cortex. Compared with the controls, urinary NAG, ALP activities, and the levels of GSH, MDA, and the activities of PKC, Na(+)-K(+)-ATPase, and Ca(2+)-ATPase in rats from the Cd-treated group were significantly increased. SOD activity was suppressed by Cd. Urinary NAG activity and the level of GSH and the activities of PKC and Ca(2+)-ATPase in both CPZ and Ver pre-treated groups were significantly lower than that in Cd-treated rats. The present results showed that Cd-induced kidney damage was related to the oxidative damage and disturb intracellular Ca2+ homeostasis. Both CPZ and Ver possess some ability to prevent cadmium-induced kidney damage via antioxidative action and by maintaining calcium homeostasis.
Xu
Bin
B
Department of Environmental Health, School of Public Health, China Medical University, North 2nd Road 92, Heping Ward, Shenyang, Liaoning 110001, People's Republic of China.
Xu
Zhao-Fa
ZF
Deng
Yu
Y
Yang
Jing-Hua
JH
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002104:Cadmium / Q000032:analysis / Q000652:urine; D002105:Cadmium Poisoning / Q000188:drug therapy*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology*; D005260:Female; D007668:Kidney / Q000737:chemistry / Q000187:drug effects*; D007672:Kidney Cortex / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*
D000975:Antioxidants; D002121:Calcium Channel Blockers; D002104:Cadmium; D014700:Verapamil; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002746:Chlorpromazine