Dexamethasone prevents acute cadmium-induced hepatic injury but exacerbates kidney dysfunction in rabbits.
Cadmium is a potent hepatotoxicant for which neither effective preventive methods nor the mechanism of toxicity has been established. We investigated the preventive effect of dexamethasone against cadmium toxicity on cadmium-induced liver injury in rabbits. Pretreatment with dexamethasone at 1 mg/kg increased the rate of survival in rabbits administered 2.5 mg/kg iv cadmium. Cadmium induced acute severe liver injury characterized by hepatocellular necrosis, infiltration by inflammatory cells, and increases of plasma GOT, GPT, LDH, and LDH5. Dexamethasone mitigated the acute hepatotoxic effect of cadmium, but exacerbated cadmium-induced kidney dysfunction, with destruction of renal tubular cells and increases in excretion of protein, glucose, and amino acids into urine. The cadmium concentration in liver and kidney of rabbits administered cadmium was not changed by dexamethasone pretreatment. Although metallothionein mRNA expression induced by cadmium was not affected by dexamethasone in liver or kidney, cadmium-induced metallothionein protein production was augmented at the early phase in liver and decreased at the later phase in kidney. Neutrophilia observed after cadmium administration was enhanced initially by dexamethasone pretreatment. These results indicate that dexamethasone pretreatment potently prevented cadmium-induced liver injury, but exacerbated renal tubular dysfunction.
Horiguchi
H
H
Department of Public Health, School of Medicine, Fukushima Medical University, 1 Hikarigoaka, Fukushima, 960-1295, Japan. hhyogo@jichi.ac.jp
Oguma
E
E
Kayama
F
F
Sato
M
M
Fukushima
M
M
D000596:Amino Acids / Q000652:urine; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000633:toxicity; D001806:Blood Urea Nitrogen; D002104:Cadmium / Q000032:analysis / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D003404:Creatinine / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008668:Metallothionein / Q000096:biosynthesis; D011507:Proteinuria / Q000209:etiology; D011817:Rabbits; D015996:Survival Rate; D013997:Time Factors
D000596:Amino Acids; D000893:Anti-Inflammatory Agents; D002104:Cadmium; D003907:Dexamethasone; D008668:Metallothionein; D003404:Creatinine