Differential effect of peroxisome proliferators on rat glutathione S-transferase isoenzymes.

We have investigated the effects of peroxisome proliferators silvex, nafenopin and diethylhexylphthalate (DEHP) on rat liver glutathione S-transferase (GST) isoenzyme activities and patterns. Silvex was a more potent in vitro GST inhibitor than nafenopin and DEHP. After 14 days oral administration to rats a reduction in total GST activity was observed, doses of compounds were chosen so that peroxisome proliferation was equivalent between compounds, nevertheless total GST activity was altered to different extents: nafenopin approximately silvex > DEHP approximately control. GST isoenzyme profiles were also altered, the proportion of GST 2-2 increased and 4-4 decreased compared to control levels. The results indicated that: (i) the peroxisome proliferators studied had similar effects on GST isoenzyme profile: (ii) modulation of the GST activity was apparently independent of peroxisome proliferation per se.