2,3,7,8 Tetrachlorodibenzo- P-dioxin induces oxygen activation associated with cell respiration

• Published in: Free radical biology & medicine Vol. 6; no. 4; pp. 369 - 374
• Main Authors: Nohl, Hans, de Silva, Deepika, Summer, Karl-Heinz
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 1989; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Catalase - metabolism; Cattle; Chemical and industrial products toxicology. Toxic occupational diseases; Cytochrome b Group - metabolism; Cytochrome c Group - metabolism; Dioxins - pharmacology; Electron Transport - drug effects; Energy conservation; Inhibition of mitochondrial respiration; Kinetics; Medical sciences; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Oxidation-Reduction; Oxidative Phosphorylation - drug effects; Oxygen activation; Oxygen Consumption - drug effects; Polychlorinated Dibenzodioxins - pharmacology; Superoxide Dismutase - metabolism; Superoxides - metabolism; TCDD; Toxicology; Various organic compounds; Inhibition of mitochondrial respiration; TCDD; Oxygen activation; Energy conservation
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/0891-5849(89)90081-6

We have investigated the influence of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) on bioenergetic functions of isolated heart-mitochondria. Electron transfer and energy conservation activities were found to be decreased in the presence of very amounts of the polychlorinated biphenyl compound (1.5 nmol/mg mitochondrial protein). The effect was greatest when substrates for complex I were used. In this case coupling of oxidative phosphorylation to respiration was drastically diminished, essentially at the expense of state 3 respiration, and P/O values were found around 2 instead of 3. Succinate-related energy conservation remained practically unaffected in the presence of TCDD, suggesting an interference of the toxic compound at coupling site I. SOD plus catalase found to protect energy-linked respiration from the effect of dioxin indicating the involvement of superoxide radicals and H 2O 2 in the development of the observed phenomena. The present contribution provides experimental evidence on the formation of these oxygen species in the presence of TCDD. Furthermore, the site of action of TCDD is demonstrated and discussedd in relation to the oxygen radical formation observed.