Ml. O'Brien et al., Effects of peroxisome proliferators on antioxidant enzymes and antioxidantvitamins in rats and hamsters, TOXICOL SCI, 60(2), 2001, pp. 271-278
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.