Protective effects of the antioxidant 4b,5,9b,10-tetrahydroindeno[1,2-b]indole against TCDD toxicity in C57BL/6J mice.
The protection against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 5 microg/kg body weight) toxicity by the antioxidant 4b,5,9b,10-tetrahydroindeno[1,2-b]indole (THII) was examined in female C57BL/6J mice. TCDD produced increases in the levels of hepatic lipid-derived aldehydes, rates of mitochondrial production of hydrogen peroxide and superoxide, and the oxidation state of cytosolic GSH. In contrast, mitochondrial GSH increased in reduction state, correlating with an increase in mitochondrial membrane potential. Systemically, TCDD lowered body weight gain, percentage body fat, and hepatic ATP levels, parameters prevented by concomitant administration of 100 microM THII in drinking water. However, TCDD-induced increases in mitochondrial respiration and decreased mitochondrial membrane fluidity were not prevented by THII. These results suggest that TCDD-mediated oxidative stress was not responsible for changes in mitochondrial respiration or membrane fluidity. Furthermore, although TCDD produced a large increase in mitochondrial oxygen consumption, this was not associated with the poor gain in weight produced by TCDD.
Shertzer
Howard G
HG
University of Cincinnati Medical Center, Cincinnati, OH, USA. shertzhg@ucmail.uc.edu
D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D010101:Oxygen Consumption; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015430:Weight Gain
D000975:Antioxidants; D004785:Environmental Pollutants; D007211:Indoles; D000072317:Polychlorinated Dibenzodioxins; D017382:Reactive Oxygen Species; C090686:4b,5,9b,10-tetrahydroindeno(1,2-b)indole; D008315:Malondialdehyde; D005978:Glutathione