Liver and kidney function and histology in rats exposed to cadmium and ethanol.
OBJECTIVE
The present study was performed to assess the function and histology of the liver and kidney in rats exposed to 50 mg Cd/l (as cadmium chloride) and/or 10% (w/v) ethanol (EtOH) for 12 weeks.


METHODS
The activities of alanine aminotransferase (ALAT) and asparate aminotransferase (AspAT) in serum were measured as indicators of the liver function. As parameters of the kidney function, creatinine, total protein and urea concentrations in serum and urine, as well as urinary alkaline phosphatase (ALP) activity were determined, and creatinine clearance was calculated. Both organs were subjected to histopathological analysis.


RESULTS
Daily Cd intake ranged from 3.17 to 4.28 mg/kg body weight and from 2.41 to 3.17 mg/kg body weight in the Cd and Cd + EtOH groups, respectively. The daily intake of 10% EtOH ranged from 47.5 to 86.9 g/kg body weight in the EtOH and from 47.3 to 63.4 g/kg body weight in the Cd + EtOH-exposed rats. Cd and EtOH, independently of separate or combined application, changed liver and kidney function and histology. Rats treated with Cd alone and those co-exposed to both substances showed qualitatively similar, but different magnitudes of changes, in liver and kidney histology. Blurred trabecular structure, vacuolar degeneration and increased density of nuclear chromatin with very compact nuclear structure were found in hepatocytes of zones 2 and 3. Moreover, mononuclear cell infiltrations and necrosis of single cells were evident in zone 1. In the kidney tubules, degeneration and hypertrophy of epithelial cells and dilation in the glomeruli were also observed. Some functional (increased serum AspAT and urinary ALP, decreased urinary urea) and structural changes in the liver and kidney were more evident in the case of combined exposure, while others were more evident after single exposure. However, a decrease in creatinine clearance, noted only in the animals treated with Cd and EtOH, shows that functional changes indicating renal insufficiency are more serious in the co-exposed group.


CONCLUSIONS
Due to lower Cd and EtOH intake (resulting from a stronger aversion to drinking water containing both substances) in the co-exposed rats, as compared to the Cd- and EtOH-treated groups, it is difficult to draw a definite conclusion from this study. The findings, however, seem to indicate that EtOH increases Cd nephrotoxicity in rats, and thus may suggest a higher risk of kidney damage in alcoholics exposed to Cd. Unfortunately, this study does not provide clear evidence if, and to what extent, EtOH influences Cd hepatotoxicity.
Brzóska
M M
MM
Department of Toxicology, Medical Academy, Mickiewicza 2c str., 15-222 Bialystok, Poland.
Moniuszko-Jakoniuk
J
J
Piłat-Marcinkiewicz
B
B
Sawicki
B
B
D000435:Alcoholic Intoxication / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics; D002105:Cadmium Poisoning / Q000473:pathology / Q000503:physiopathology*; D004357:Drug Synergism; D000431:Ethanol / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017093:Liver Failure / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology
D002104:Cadmium; D000431:Ethanol