[Effect of diclofop on the activity of some drug-metabolizing enzymes in the liver of male Wistar rats].
The study was designed to determine whether diclofop, introduced to environment as herbicide, would exert properties of chemical inducers of rat liver monooxygenase system related to CYP1A and CYP2B isozymes. For this purpose, the effect of diclofop on 7-etoxyresorufin O-dealkylase and p-nitroanisole O-demethylase activities specific for CYP1A as well as on CYP2B mediated 7-pentoxyresorufin O-dealkylase activity was studied in male Wistar rats. This biochemical method permits to determine whether tested compound belongs to one of two main types of chemical inducers. Diclofop was dosed by gavage for 4 days at 0; 5.6, 11.2 and 56 mg/kg b.w. per day. Treatment of rats with diclofop resulted in significant increase in relative liver weight (RLW), to 19% and 31% above the control, respectively. Diclofop administered at the dose of 11.2 and 56 mg/kg b.w. per day induced a 3-fold (p < 0.001) and a 5-fold (p < 0.001) increase in the metabolism of 7-pentoxyresorufin (CYP2B-mediated reaction), respectively. No effect level for CYP2B induction was 5.6 mg/kg b.w per day. However, diclofop induced only slight increase in 7-etoxyresorufin O-dealkylase and did not show any effect on p-nitroanisole O-demethylase activity (CYP1A-mediated reactions). The results revealed that diclofop not show the ability to induce CYP1A and moreover it was weak inducer of CYP2B isozymes in the liver of male Wistar rats. Diclofop was also examined for its ability to affect the activity of phenol UDP-glucuronosyltransferase in rat liver. The results suggest that diclofop suppressed phenol form of UDP-glucuronosyltransferase activity. The isozyme activity decreased by 50% and 35% at the dose of 11.2 and 56 mg/kg b.w. per day, respectively. It should be noted that this form of enzyme inactivates during II phase of biotransformation most chemical carcinogens and other xenobiotics.
Palut
Danuta
D
Zakład Toksykologii Srodowiskowej Państwowy Zakład Higieny, 00-791 Warszawa.
Kostka
Grazyna
G
Wiadrowska
Bozena
B
Bańkowski
Robert
R
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000378:metabolism*; D019362:Cytochrome P-450 CYP2B1 / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D055768:Halogenated Diphenyl Ethers; D006540:Herbicides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010647:Phenyl Ethers / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D055768:Halogenated Diphenyl Ethers; D006540:Herbicides; D010647:Phenyl Ethers; C012891:dichlorfop-methyl; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1
Wpływ diklofopu na wybrane enzymy metabolizujace substancje obce w watrobie szczurów rasy wistar.