Abstract
The exhalation of ethane is widely used as an indicator of in vivo lipid peroxidation. To test the hypothesis that lipid peroxidative events are involved in the toxicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), we administered a lethal dose of TCDD (60 μg/kg), IP to male Sprague Dawley rats (160–180 g) and measured by gas chromatography the exhalation of ethane into the atmosphere of a closed all-glass exposure chamber. TCDD-treated rats exhaled only slightly more ethane than control rats at a single time point 7 days following TCDD administration. Since the exhalation of ethane is the net result of the endogenous production of the gas and its metabolic degradation, the latter was quantified by measuring the clearance of exogenous ethane (initial concentration = 100 ppm) introduced to the atmosphere of the exposure chamber. The clearance of ethane in TCDD-treated rats was markedly decreased, reaching a minimum 7 days following TCDD treatment. Apparently, the slight increase in exhaled ethane was due to an inhibition of ethane metabolism caused by TCDD. However, rats obviously intoxicated and having lost considerable body weight might be impaired in their ability to transport ethane. To bypass this problem we injected ethane (0.2 ml) directly into the rats IP. Here also the metabolic clearance in TCDD-treated rats was diminished. In a further experiment, rats treated with dithiocarb at a dose where ethane metabolism was totally inhibited exhaled more ethane than did TCDD-treated rats. It is therefore concluded that the slight increase in ethane exhalation following a lethal dose of TCDD is due to a partial inhibition of ethane metabolism and that there is no net increase in ethane production due to lipid peroxidation. Indeed when TCDD-treated rats were administered Fe++, a well-known initiator of lipid peroxidation, they were less competent to carry out lipid peroxidation than rats treated with Fe++ alone.
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References
Albro PW, Corbett JT, Harris M, Lawson LD (1978) Effects of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin on lipid profiles in tissue of the fisher rat. Chem Biol Interact 23: 315–330
Andersen ME (1981) A physiologically based toxicokinetic description of the metabolism of inhaled gases and vapors: Analysis at steady state. Toxicol Appl Pharmacol 60: 509–526
Aust SD, Svingen BA (1982) The role of iron in enzymatic lipid peroxidation. In: Pryor WA (ed) Free Radicals in Biology Vol V Academic Press, New York pp 1–28
Bernert JT Jr, Groce DF, Kimbrough RD (1983) Long-term effects of a single oral dose of polybrominated biphenyls on serum and liver lipids in rats. Toxicol Appl Pharmacol 68: 424–433
Bolt, HM, Filser, JG, Störmer F (1984) Inhalation pharmacokinetics based on gas uptake studies V. Comparative pharmacokinetics of ethylene and 1, 3-butadiene in rats. Arch Toxicol 55: 213–218
Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52: 302–310
De Ruiter N, Ottenwälder H, Muliawan H, Kappus H (1981) Ethane formation of isolated rat hepatocytes due to carbon tetrachloride. Toxicol Lett 8: 265–271
Filser, JG, Bolt, HM (1981) Inhalation pharmacokinetics based on gas uptake studies I. Improvement of kinetic models. Arch Toxicol 47: 279–292
Filser, JG, Bolt HM (1983) Inhalation pharmacokinetics based on gas uptake studies IV. The endogenous production of volatile compounds. Arch Toxicol 52: 123–133
Filser JG, Bolt HM, Muliawan H, Kappus H (1983) Quantitative evaluation of ethane and n-pentane as indicators of lipid peroxidation in vivo. Arch Toxicol 52: 135–147
Frank H, Hintze T, Bimboes D, Remmer H (1980) Monitoring lipid peroxidation by breath analysis: Endogenous hydrocarbons and their metabolic elimination. Toxicol Appl Pharmacol 56: 337–344
Hassan MQ, Stohs, SJ, Murray WJ (1983) Comparative ability of TCDD to induce lipid peroxidation in rats, guinea pigs, and Syrian golden hamsters. Bull Environ Contam Toxicol 31: 649–657
Poland A, Knutson JC (1982) 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: Examination of the mechanism of toxicity. Ann Rev Pharmacol Toxicol 22: 517–554
Riely CA, Cohen, G, Lieberman M (1974) Ethane evolution: A new index of lipid peroxidation. Science 183: 208–210
Robertson LW, Andres JL, Safe SH, Lovering SL (1983) Toxicity of 3,3′, 4,4′- and 2,2′, 5,5′-tetrabromobiphenyl: Correlation of activity with aryl hydrocarbon hydroxylase induction and lack of protection by antioxidants J Toxicol Environ Health 11: 81–91
Siegers, C-P, Filser JG, Bolt HM (1978) Effect of dithiocarb on metabolism and covalent binding of carbon tetrachloride. Toxicol Appl Pharmacol 46: 709–716
Stohs SJ, Hassan MQ, Murray WJ (1983) Lipid peroxidation as a possible cause of TCDD toxicity. Biochem Biophys Res Commun 111: 854–859
Sweeney GD (1981) The heme biosynthetic pathway in the prediction of haloaromatic hydrocarbon toxicity. In: Yoshida H, Higihara Y, Ebashi S (eds) Advances in pharmacology and therapeutics, II, Vol 5, Toxicology and experimental models Pergamon Press, New York pp 147–159
Sweeney GD, Jones KG, Cole FM, Basford D, Krestynski F (1979) Iron deficiency prevents liver toxicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. Science 204: 332–335
Tappel AL (1980) Measurement of and protection from in vivo lipid peroxidation. In: Pryor WA (ed) Free radicals in biology Vol IV Academic Press, New York pp 7–4
Thelen M, Wendel A (1983) Drug-induced lipid peroxidation in mice — V. Ethane production and glutathione release in the isolated liver upon perfusion with acetaminophen. Biochem Pharmacol 32: 1701–1706
Thomas PE, Reik LM, Ryan DE, Levin W (1983) Induction of two immunochemically related rat liver cytochrome P-450 isozymes, cytochromes P-450c and P-450d, by structurally diverse xenobiotics. J Biol Chem 258: 4590–4598
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This work is part of the M.D. thesis of U. Regel
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Robertson, L.W., Regel, U., Filser, J.G. et al. Absence of lipid peroxidation as determined by ethane exhalation in rats treated with 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). Arch Toxicol 57, 13–16 (1985). https://doi.org/10.1007/BF00286568
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DOI: https://doi.org/10.1007/BF00286568