Changes in hepatic cytosolic glutathione S-transferase enzymes induced by clotrimazole treatment in rats.
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-nitro-benzyl 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.
González
P
P
Department of Physiology, Pharmacology and Toxicology, University of León, Spain.
Tuñón
M J
MJ
Manrique
V
V
Garcia-Pardo
L A
LA
González
J
J
D000818:Animals; D003022:Clotrimazole / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology*; D004790:Enzyme Induction; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D007093:Imidazoles; D005982:Glutathione Transferase; D003022:Clotrimazole