Effect of s-triazine and phenoxyalkanoic acid herbicides on UDP-glucuronosyltransferase in rat liver microsomes

Twelve herbicides, representatives of two chemical groups, substituted phen oxyalkanoic acids and s-triazines, were tested for their inhibitory effect on the glucuronidation of 4-nitrophenol (4-NP), phenolphthalein (PPh) and 4 -methylumbelliferone (4-MU) by rat liver microsomes. One millimole MCPA, am etryn and cyanazine significantly decreased PPh UDP-glucuronosyltransferase (UGT) activity, while propazine was found to be a most potent inhibitor of 4-NP glucuronidation. Concentrations of 0.1 mM dichlorprop and cyanazine w ere still inhibitory against PPh-UGT. The inhibition of 4-MU glucuronidatio n by the herbicides was low and not specific. As a whole, s-triazine deriva tives were more inhibitory than the substituted phenoxyallianoic acids. Kin etic studies with propazine revealed a non-competitive type of inhibition t owards the acceptor substrate 4-NP, with an apparent K-i value of 0.540 mM. With ametryn, an uncompetitive type of inhibition against PPh and a mixed type of inhibition towards UDPGA were found, with apparent Ki values of 0.3 30 mM and 0.380 mM, respectively. (C) 1999 Society of Chemical Industry.