Effects of peroxisome proliferators on antioxidant enzymes and antioxidantvitamins in rats and hamsters

Peroxisome proliferators (PPs) cause hepatomegaly, peroxisome proliferation , and hepatocarcinogenesis in rats and mice, whereas hamsters are less resp onsive to PPs. PPs increase the activities of enzymes involved in peroxisom al P-oxidation and omega -hydroxylation of fatty acids, which has been hypo thesized to result in oxidative stress. The hypothesis of this study was th at differential modulation of antioxidant enzymes and vitamins might accoun t for differences in species susceptibility to PPs. Accordingly, we measure d the activities of DT-diaphorase and superoxide dismutase (SOD) and the he patic content of ascorbic acid and cu-tocopherol in male Sprague-Dawley rat s and Syrian hamsters fed 2 doses of 3 known peroxisome proliferators (dibu tyl phthalate [DBP], gemfibrozil, and [4-chloro-6-(2,3-xylidino)-2-pyrimidi nylthio]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, b ut the control levels of SOD, ascorbic acid and alpha -tocopherol were simi lar. In rats and hamsters treated with Wy-14,643, we observed decreases in alpha -tocopherol content and total SOD activity. DT-diaphorase was decreas ed in activity following Wy-14,643 treatment in rats at all time points and doses, but only sporadically affected in hamsters. Rats and hamsters treat ed with DBP demonstrated increased SOD activity at 6 days; however, in the rat, DBP decreased SOD activity at 90 days and cu-tocopherol content was de creased throughout. In gemfibrozil treated rats and hamsters, a decrease in cu-tocopherol content and an increase in DT-diaphorase activity were obser ved. 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 anti-; oxidant capa bilities following PP treatment and additional hypotheses for species susce ptibility should be considered.