2,3,7,8, tetrachlorodibenzo-p-dioxin induces oxygen activation associated with cell respiration.
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 low 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 were found to protect energy-linked respiration from the effect of dioxin indicating the involvement of superoxide radicals and H2O2 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 discussed in relation to the oxygen radical formation observed.
Nohl
H
H
Institute of Pharmacology and Toxicology, Veterinary University of Vienna, Austria.
de Silva
D
D
Summer
K H
KH
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002417:Cattle; D003573:Cytochrome b Group / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004147:Dioxins / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D007700:Kinetics; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D003573:Cytochrome b Group; D003574:Cytochrome c Group; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D013481:Superoxides; D002374:Catalase; D013482:Superoxide Dismutase