Dietary effects on inhibition of rat hepatic microsomal drug-metabolizing enzymes by a pesticide (Morestan).

Female rats were fed for 21 days on 5 semi-synthetic diets containing 8 or 30% proteins, 1 or 25% lipids respectively, the control animals being given a diet containing 20% proteins and 5% lipids. The animals on each diet were then subdivided into two subgroups and on the 22nd, 23rd, 24th and 25th days were given an oral dose of 75 mg/kg of Morestan in solution in peanut oil (PO) or a dose of oil only. The microsomes were prepared 24 h after the last administration and aniline aromatic hydroxylase, aminopyrine and N-methylaniline N-demethylase activities and cytochrome P-450, protein and RNA levels were measured. Whatever the diet, Morestan inhibited N-demethylase activities and decreased the cytochrome P-450 level; liver protein and RNA levels and microsomal RNA level increased. The 25% lipid diet alone increased activity of the three enzymes studied, without modifying the cytochrome P-450 level; Morestan produced antagonism of this effect in the rats on this diet. The decreased cytochrome P-450 level caused by Morestan was higher in animals on the 8% protein diet.