Lipid peroxidation, calcium, iron, and TCDD toxicity in rats
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been studied as a prototype of halogenated aromatic hydrocarbons. Previous studies have shown that TCDD enhances hepatic lipid peroxidation. This study on TCDD administration to rats was conducted to: measure induction of lipid peroxidation in hepatic and extrahepatic tissues; compare lipid peroxidation between sexes; determine the contributions of H/sub 2/O/sub 2/ and other reactive oxygen species and associated enzymes on hepatic lipid peroxidation: determine the role of iron in TCDD-induced lipid peroxidation; and investigate the relationship between TCDD-induced alterations in lipid peroxidation, calcium homeostasis, reduced glutathione content (GSH) and selenium-dependent glutathione peroxidase activity (GSH-Px). The results demonstrated that TCDD induces changes in microsomal lipid peroxidation in hepatic and extrahepatic tissues. The rates of microsomal lipid peroxidation in male rats were less than in microsomes from female rats. TCDD treatment produced a significant increase in lipid peroxidation which preceded an increase in whole homogenate and mitochondrial calcium content, but paralleled an increase in microsomal calcium content. TCDD treatment produced dose and time dependent decreases in hepatic GSH content and GSH-Px activity in female rats. H/sub 2/O/sub 2/ and possibly hydroxyl radical and singlet oxygen are involved in TCDD-induced hepatic microsomal lipid peroxidation. The results support the hypothesis that the toxicity of TCDD and its lack of tissue selectivity in male and female rats may be due in part to lipid peroxidation. Lipid peroxidation may alter membrane permeability to calcium and lead to sequestration of calcium.
- Research Organization:
- Nebraska Univ., Omaha (USA). Medical Center
- OSTI ID:
- 6785148
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH METAL COMPOUNDS
ANIMALS
AROMATICS
BODY
CALCIUM COMPOUNDS
CELL CONSTITUENTS
CELL MEMBRANES
CHEMICAL REACTIONS
CHLORINATED AROMATIC HYDROCARBONS
DIGESTIVE SYSTEM
DIOXIN
DRUGS
ENZYMES
GLANDS
GLUTATHIONE
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
IRON COMPOUNDS
LIPIDS
LIVER
MAMMALS
MEMBRANES
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDATION
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEPTIDES
PERMEABILITY
PEROXIDASES
PEROXIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
SELENIUM COMPOUNDS
SEX DEPENDENCE
TOXICITY
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES