Metallothionein induction and its protective effect in liver and kidney of rats exposed to cadmium chloride

Kim, Nam Song; Lee, Jae Hyung; Koh, Dai Ha; Ki, No Suk; Hwang, In Dam

Abstract

Tolerance to several toxic effects of cadmium, including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity and renal toxicity. Three groups of rats (A, B, C), each consisting of 16 rats, were studied and each group was divided into four subgroups (1, 2, 3, 4), 4 rats for each subgroup. Rats were subcutaneously pretreated with saline (A), CdCl2(0.5 mg/kg, B), and ZnCl2 (13.0 mg/kg, C) during time periods of 1~6 weeks. At the end of the period, rats were challenged with CdCl2 (3.0, 6.0 and 9.0 mg/kg, ip). After giving the challenge dose, cadmium and metallothionein (MT) concentrations were determined and also observed the histologic change in liver and kidney. The concentration of cadmium in liver and also observed the increased dose-dependently to the challenge dosage. These data indicate the kidney is a major target organ of chronic cadmium poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play and important role in the nephrotoxicity observed in response to long-term exposure to cadmium. In addition, histologic examination of group A2, A3 and A4 revealed moderate to severe cadmium toxicity, evidenced by infiltration of inflammatory cells, cell swelling, pyknosis, enlarged sinusoids and necrosis in liver, and tubule cell necrosis and degeneration in kidney. However, MT concentrations in liver and kidney were increased by the pretreatment of CdCl2 and ZnCl2 and their morphological findings were not significantly changed, comparing with control group. Higher MT concentration in liver and kidney observed in the pretreated groups constitutes a plausible explanation of the protective effects of pretreatment against the cadmium toxicity after challenge dosing.