Effects of BHA, d-alpha-tocopherol and retinol acetate on TCDD-mediated changes in lipid peroxidation, glutathione peroxidase activity and survival.
Daily treatment of female rats with butylated hydroxyanisole (BHA) protected against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity. This protective effect was associated with reduced microsomal lipid peroxidation, increased glutathione peroxidase (GSH-PX) activity and decreased aryl hydrocarbon hydroxylase (AHH) activity. Retinol acetate (vitamin A) inhibited lipid peroxidation, elevated GSH-PX activity, and enhanced AHH activity. Thirty per cent of vitamin A-treated animals were alive 25 d after a lethal dose of TCDD. d-alpha-Tocopherol (vitamin E) inhibited markedly microsomal lipid peroxidation, enhanced AHH activity, and had no effect on GSH-PX activity. Only 10% of the vitamin E-treated animals were alive 25 d after a lethal dose of TCDD. The mechanism of TCDD toxicity may involve in part inhibition of GSH-PX activity with resultant lipid peroxidation by hydrogen peroxide.
D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D004147:Dioxins / Q000633:toxicity*; D004224:Diterpenes; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009026:Mortality; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D000084562:Retinyl Esters; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology*
D000840:Anisoles; D004147:Dioxins; D004224:Diterpenes; D008054:Lipid Peroxides; D000072317:Polychlorinated Dibenzodioxins; D000084562:Retinyl Esters; D014801:Vitamin A; D014810:Vitamin E; D002083:Butylated Hydroxyanisole; C009166:retinol acetate; D005979:Glutathione Peroxidase; D001189:Aryl Hydrocarbon Hydroxylases