Alterations of the glutathione redox cycle status in fumonisin B1-treated pig kidney cells.
Fumonisin B1 (FB1) causes equine leukoencephalomalacia, porcine pulmonary edema, and liver tumors and chronic nephritis in rats. To investigate mechanisms by which FB1 induces toxicity, effects of FB1 on cellular glutathione (GSH) redox status and GSH depletion on FB1 toxicity in pig kidney (LLC-PK1) cells were studied. Treatment of LLC-PK1 cells with 50 microM FB1 for 24 hours significantly decreased cellular GSH contents from 56 +/- 3.2 to 42.7 +/- 4.4 nmol/mg protein (p < 0.05) and increased the activities of glutathione reductase (GR) from 25.7 +/- 2.4 to 35.7 +/- 5.0 mumol NADPH/mg protein (p < 0.05). The activities of glutathione peroxidase (GSHpx), catalase, and Cu,Zn-superoxide dismutase (SOD) were not changed by this treatment. Treatment of LLC-PK1 cells for 12 hours with 0.1 mM buthionine sulfoximine (BSO), a selective inhibitor of the enzyme gamma-glutamylcysteine synthetase that catalyzes the rate-limiting reaction in de novo GSH synthesis, decreased cellular GSH levels to about 20% of that found in the control cells. The cells pretreated with 0.1 mM BSO for 12 hours were significantly sensitized to the FB1 cytotoxicity as determined by a long-term survival assay (p < 0.05). The results demonstrate that FB1 changes GSH redox cycle status in LLC-PK1 cells, and GSH may play a role in cytoprotection against FB1 toxicity.
Kang
Y J
YJ
Department of Medicine, University of Louisville, School of Medicine, Kentucky 40292, USA.
Alexander
J M
JM
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002264:Carboxylic Acids / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002374:Catalase / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D037341:Fumonisins; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009183:Mycotoxins / Q000633:toxicity*; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000187:drug effects; D013552:Swine
D002264:Carboxylic Acids; D002274:Carcinogens, Environmental; D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1; D019328:Buthionine Sulfoximine; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D000111:Acetylcysteine