INFLUENCE OF PESTICIDES ON UDP-GLUCURONOSYLTRANSFERASE IN RAT-LIVER MICROSOMES

Fifteen pesticides, representatives of different chemical groups, were tested for their inhibitory effect on the glucuronidation of 4-nitrop henol (4-NP) and phenolphthalein (PPh) by rat liver microsomes. Three herbicides (simazine, chlorsulfuron, tribenuron-methyl), two insectici des (dioxacarb, carbaryl) and one fungicide (zineb) significantly decr eased the UDP-glucuronosyltransferase (UDPGT) activity. The carbamate insecticide dioxacarb was found to be the most potent inhibitor, at 1 mM concentration suppressing 4-NP-UDPGT activity completely, and reduc ing by 55% the activity associated with the conjugation of PPh. One mi llimole simazine and carbaryl affected only 4-NP glucuronidation, whil e chlorsulfuron and zineb exerted a marked inhibition of both 4-NP and PPh conversion. Concentrations of 0.1 mM carbaryl, dioxacarb and zine b were still inhibitory against 4-NP-UDPGT, with zineb producing 40% i nhibition of PPh glucuronidation. As a whole, UDPGT isoforms conjugati ng PPh were less sensitive to the agrochemicals tested. Kinetic studie s with dioxacarb, chlorsulfuron and carbaryl revealed a mixed type of inhibition with respect to the acceptor substrate 4-NP, with apparent K-i values of 70 mu M, 120 mu M and 160 mu M, respectively.