Absence of lipid peroxidation as determined by ethane exhalation in rats treated with 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)

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.