Vitamin E, diethylmaleate and bromotrichloromethane interactions in oxidative damage in vivo.

In vivo interactions of vitamin E with diethylmaleate (DEM) and bromotrichloromethane (CBrCl3) were examined in rats fed a diet either without vitamin E or supplemented with 30 IU dl-alpha-tocopheryl acetate/kg. Groups of rats within each dietary group were given two injections 30 min apart. One group received two injections of the mineral oil carrier. The other groups were injected with either DEM and mineral oil, mineral oil and CBrCl3, or DEM and CBrCl3. The rats were killed 10 min after the second injection. Measurements were made of hepatic GSH, thiobarbituric acid-reactive substances (TBARS) as a lipid peroxidation index, and 11 enzymes as potential markers of oxidant damage. Special focus was placed on reactive cysteine-containing aldehyde dehydrogenase (ALDH). Although dietary vitamin E protected ALDH, the enzyme was highly susceptible to oxidant damage. ALDH activity was correlated with GSH (r = 0.83, p less than 0.001) and there was an inverse relationship between the logarithmic values of ALDH activity and TBARS (r = 0.78, p less than 0.001). Similar results were observed for a number of other enzymes when GSH depletion preceded oxidant treatment. Two-way analysis of variance revealed significant effects of vitamin E and of injection treatments on hepatic GSH. There was a significant interaction between vitamin E and the injection treatments on the activities of five enzymes. The results suggested that vitamin E and GSH functioned together to protect sensitive enzymes against oxidant stress. The sensitive enzymes may be useful markers of hepatic damage in vivo.

Comparative antioxidant effectiveness of dietary beta-carotene, vitamin E, selenium and coenzyme Q10 in rat erythrocytes and plasma.

Five groups of five weanling rats were each fed a Torula yeast-based diet either unsupplemented or supplemented with 30 mg beta-carotene/kg, 30 IU vitamin E/kg, 1 mg selenium/kg or 30 mg coenzyme Q10/kg. Elevated levels of plasma aspartate aminotransferase and alanine aminotransferase are sensitive indicators of liver damage. The former enzyme was lower (P less than 0.01) in the vitamin E-, selenium- and beta-carotene-supplemented groups than in the unsupplemented control group, and the latter enzyme was lower in the vitamin E- and selenium-supplemented groups, suggesting a relatively equal effectiveness of these three antioxidants against liver damage. Erythrocytes were tested for protection against uninduced oxidative damage or that induced by 1 mmol/L bromotrichloromethane (BrCl3C) by measuring thiobarbituric acid-reactive substances (TBARS), hemoglobin, hemolysis, protein precipitation, alanine release and several enzyme activities. In untreated erythrocytes, selenium, beta-carotene and coenzyme Q10 exhibited protection by lowering (P less than 0.05) TBARS and alanine release, but only vitamin E protected against hemolysis. In BrCl3C-treated erythrocytes, vitamin E, selenium and beta-carotene protected by decreasing (P less than 0.05) protein precipitation, whereas selenium and beta-carotene decreased alanine release. The results of this study suggested that, in a manner analogous to vitamin E and selenium, beta-carotene and coenzyme Q10 function as antioxygenic nutrients.

Carbon tetrachloride and bromotrichloromethane toxicity. Dual role of covalent binding of metabolic cleavage products and lipid peroxidation in depression of microsomal calcium sequestration.

We have investigated the importance of covalent binding and lipid peroxidation on the depression of microsomal calcium sequestration associated with in vitro metabolism of 14CCl4. Studies with CBrCl3 are also reported. In aerobic systems, promethazine was used to block lipid peroxidation, measured as malondialdehyde (MDA) generation. Effects of low levels of lipid peroxidation were tested in Fe2+-supplemented systems free of halogenated hydrocarbons. The results indicate that microsomal calcium sequestration can be depressed significantly by metabolism of either CCl4 or CBrCl3 in the absence of MDA generation, or by lipid peroxidation occurring in the absence of halogenated hydrocarbons.