Effect of thyroidectomy on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced lipid peroxidation.
Thyroid hormones have been implicated in the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Therefore, the effects of methimazole (MMI) and propylthiouracil (PTU) induced hypothyroidism and surgical thyroidectomy on several toxic manifestations of TCDD were investigated. Female rats were treated with MMI (0.50 mg/kg) for 10 or 28 days, or PTU (5.0 mg/kg) for 10 days. Other animals were surgically thyroidectomized. The animals received TCDD (100 micrograms/kg) orally or the corn oil vehicle 6 days prior to sacrifice. MMI and PTU decreased serum thyroxine (T4) levels by 27-33% while surgical thyroidectomy decreased T4 levels by 66%. TCDD alone decreased T4 levels by 67%, and similar effects occurred in MMI and PTU treated animals. TCDD produced a 9% increase in serum triiodothyronine (T3) concentrations, and neither MMI or PTU treatment for 10 days modified this effect. Neither antithyroid drug prevented TCDD induced weight loss. TCDD administration resulted in over a 300% increase in hepatic malondialdehyde (MDA) content and a 60% decrease in glutathione peroxidase activity. Neither antithyroid compound affected TCDD-induced alterations in these two parameters. TCDD enhanced MDA content by 220% and inhibited glutathione peroxidase activity by 39% in surgically thyroidectomized rats. Thus, only severe hypothyroidism produced by surgical thyroidectomy was able to partially prevent the effects of TCDD on hepatic MDA content and glutathione peroxidase activity.
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha.
S J
SJ
Hermansky
H A
HA
Mohammadpour
W J
WJ
Murray
S J
SJ
Stohs
D000818:Animals; D004147:Dioxins / Q000494:pharmacology*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism*; D008713:Methimazole / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013965:Thyroidectomy
D004147:Dioxins; D008054:Lipid Peroxides; D000072317:Polychlorinated Dibenzodioxins; D008713:Methimazole; D011441:Propylthiouracil; D005979:Glutathione Peroxidase