Dexamethasone protects cultured rat hepatocytes against cadmium toxicity: involvement of cellular thiols.
In the present study, the effects of dexamethasone on cadmium-induced toxicity were evaluated in isolated rat hepatocytes. Hepatocytes were cultured for 24 h in William's E medium containing fetal calf serum (10%), insulin (0.1 IU/ml), and glucagon (0.01 microM) in the absence or presence of 0.1 microM dexamethasone. Cadmium chloride, 5 or 10 microM, was added to the medium and the toxicity was evaluated for up to 48 h after treatment. Lactate dehydrogenase (LDH) release, the reduced and oxidized glutathione ratio (GSH/GSSG), protein-SH groups, and lipid peroxidation levels were evaluated. Cadmium induced a dose- and time-dependent LDH release in control hepatocytes at 24 h (Cd 10 microM 42%) while hepatocytes pretreated with dexamethasone showed lower necrosis (Cd 10 microM 12% at 24 h). GSH/GSSH ratio and protein-SH groups were higher while lipid peroxidation was lower in dexamethasone-treated hepatocytes as compared with untreated cells. In conclusion, cadmium toxicity was associated with an increase in intracellular oxidative stress responsible for accelerated cell death. The use of dexamethasone prevented cadmium damage, suggesting that the cytoprotective action of this hormone is related to its effect in preventing changes in thiols such as glutathione and protein-SH groups.
Ferrigno
Andrea
A
Department of Internal Medicine and Therapeutics, University of Pavia, Via Ferrata 9A, 27100, Pavia, Italy.
Gregotti
Cesarina
C
Richelmi
Plinio
P
Vairetti
Mariapia
M
D000818:Animals; D019256:Cadmium Chloride / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000502:physiology; D013997:Time Factors
D005938:Glucocorticoids; D013438:Sulfhydryl Compounds; D003907:Dexamethasone; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D019256:Cadmium Chloride