Toxicological Sciences 60, 271-278 (2001)
Copyright © 2001 by the Society of Toxicology
CARCINOGENICITY |
Effects of Peroxisome Proliferators on Antioxidant Enzymes and Antioxidant Vitamins in Rats and Hamsters
* Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536;
Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709; and
Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40536; and
§ Department of Microbiology and Immunology and Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky 40536
Peroxisome proliferators (PPs) cause hepatomegaly, peroxisome proliferation, and hepatocarcinogenesis in rats and mice, whereas hamsters are less responsive to PPs. PPs increase the activities of enzymes involved in peroxisomal ß-oxidation and 
-hydroxylation of fatty acids, which has been hypothesized to result in oxidative stress. The hypothesis of this study was that differential modulation of antioxidant enzymes and vitamins might account for differences in species susceptibility to PPs. Accordingly, we measured the activities of DT-diaphorase and superoxide dismutase (SOD) and the hepatic content of ascorbic acid and 
-tocopherol in male Sprague-Dawley rats and Syrian hamsters fed 2 doses of 3 known peroxisome proliferators (dibutyl phthalate [DBP], gemfibrozil, and [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) for 6, 34, or 90 days. In untreated animals, the activity of DT-diaphorase was much higher in hamsters than in rats, but the control levels of SOD, ascorbic acid and -tocopherol were similar. In rats and hamsters treated with Wy-14,643, we observed decreases in -tocopherol content and total SOD activity. DT-diaphorase was decreased in activity following Wy-14,643 treatment in rats at all time points and doses, but only sporadically affected in hamsters. Rats and hamsters treated with DBP demonstrated increased SOD activity at 6 days; however, in the rat, DBP decreased SOD activity at 90 days and -tocopherol content was decreased throughout. In gemfibrozil treated rats and hamsters, a decrease in -tocopherol content and an increase in DT-diaphorase activity were observed. In either species, no consistent trend was observed in total ascorbic acid content after treatment with any of the PPs. In conclusion, these data suggest that both rats and hamsters are compromised in antioxidant capabilities following PP treatment and additional hypotheses for species susceptibility should be considered.
Key Words: Wy-14; 643; dibutyl phthalate; gemfibrozil; superoxide dismutase; DT-diaphorase; -tocopherol; ascorbic acid; peroxisome proliferator (PP); Sprague-Dawley rat; Syrian hamster.
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