CHANGES IN HEPATIC CYTOSOLIC GLUTATHIONE S-TRANSFERASE ENZYMES INDUCED BY CLOTRIMAZOLE TREATMENT IN RATS

SUMMARY 1. The influence of the antifungal agent clotrimazole on cytosolic glutathione S‐transferase activities was studied in male Wistar rats. 2. Animals received clotrimazole by gastric lavage for 3 days (75 mg/kg per day). Hepatic glutathione S‐transferase activity was determined with five different substrates: 1‐chloro‐2,4‐dinitrobenzene (CDNB), 1,2‐dichloro‐4‐nitrobenzene (DCNB), p‐nitrobenzyl chloride (PNBC), ethacrynic acid (EA) and trans‐4‐phenyl‐3‐buten‐2‐one (TPBO). 3. The largest increases in glutathione S‐transferase activity were found with CDNB, DCNB and PNBC (+ 61%, + 50% and + 50%, respectively, when expressed per mg of cytosolic protein). Enzyme activity toward EA was induced to a lower extent (+ 33%). Changes in the formation of the conjugate of TPBO were relatively small (+22%). 4. These data indicate a differential induction of glutathione S‐transferase isoenzymes and suggest that clotrimazole is a phenobarbital‐type inducer of enzyme activity.