Ovariectomy enhances cadmium-induced nephrotoxicity and hepatotoxicity in rats.
The toxicity of cadmium (Cd) chloride was studied in ovariectomized (OX) female rats and non-OX female rats after intravenous administration of the compound at doses of 2.0 and 3.0 mg/kg for 14 days. Mild hypochromic microcytic anemia developed in all rats treated with Cd, but growth retardation in the OX rats was more prominent than that in the non-OX rats. There was an increase of AST and ALT and a decrease of total cholesterol and the A/G ratio in both OX and non-OX rats treated with Cd. The hepatic and renal Cd concentrations increased in a dose-dependent manner, and the concentrations in both organs on Day 14 were comparable in the 3.0 mg/kg OX group (liver, 270.0 +/- 39.6 micrograms/g; kidney, 121.3 +/- 10.1 micrograms/g) and non-OX group (liver, 277.0 +/- 29.9 micrograms/g; kidney, 100.8 +/- 1.3 micrograms/g). Hepatocyte necrosis developed only in OX rats treated with Cd, and the nephrotoxicity of Cd was also notably enhanced by ovariectomy, since Cd nephropathy affected the proximal convoluted epithelium more severely and more frequently in OX rats than in non-OX rats. BrdU-labeled cells in the renal cortex were increased by approximately 2.7-fold in OX rat (7.4 cells/mm2) over those in the renal cortex in non-OX rat (2.7 cells/mm2). In conclusion, the present study demonstrated that ovariectomy enhanced Cd-induced nephrotoxicity and hepatotoxicity in rats.
Katsuta
O
O
Mitsubishi Kasei Institute of Toxicological and Environmental Sciences, Ibaraki, Japan.
Hiratsuka
H
H
Matsumoto
J
J
Tsuchitani
M
M
Umemura
T
T
Marumo
F
F
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002104:Cadmium / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D008854:Microscopy, Electron; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
D002104:Cadmium