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.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005659:Fungicides, Industrial / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology*; D012313:RNA / Q000378:metabolism; D051381:Rats
D005659:Fungicides, Industrial; D011506:Proteins; D011810:Quinoxalines; D012313:RNA; C005266:quinomethionate; D003577:Cytochrome P-450 Enzyme System; D010089:Oxidoreductases, N-Demethylating