Acute exposure to cadmium causes severe liver injury in rats

The acute cardiotoxicity of Cd was studied in rats injected iv with 3.9 mg Cd/kg (LD99). Electrocardiogram, blood pressure, and heart rate were recorded intermittently from 9 hr after Cd administration until death. No changes were observed in cardiac indices. Microscopic examination of the major tissues revealed histologically normal myocardium but severely damaged liver. To evaluate further the observed hepatotoxic effects of Cd, time course (1 to 10 hr after 3.9 mg Cd/kg, iv) and dose-response (10 hr after 0.9 to 3.9 mg Cd/kg, iv) studies were conducted. Liver was examined for histopathologic changes; plasma enzyme activities of aspartate (AST) and alanine (ALT) aminotransferases and alkaline phosphatase (AP) were determined to assess liver damage. Pronounced eosinophilia, hepatocyte swelling, and an increase of mitotic figures in hepatocytes were present within 1 hr after Cd. Increased AST and ALT activities were also observed, but AP activity and plasma glucose concentration were unchanged. At later times, severe liver injury was evidenced by necrosis of hepatocytes, striking elevation of serum enzymes (AST, ALT, and AP), and a 50% decrease in plasma glucose concentration. Doseresponse data indicated that doses greater than 1.1 mg Cd/kg produced pathologic changes similar to those observed in the time course study 1 hr after 3.9 mg Cd/kg. Doses above 3.5 mg Cd/kg caused massive hepatic necrosis and increased ALT, AST, and AP activities 60-, 100-, and 3-fold, respectively. A 50% decrease in plasma glucose concentration was also observed at doses above 2.9 mg Cd/kg. These results do not suggest that Cd is cardiotoxic after acute exposure, but rather that the liver is a major target organ for acute Cd toxicity.