The influence of thiamin deficiency on the metabolism of the oral contraceptive mestranol [3-methoxy-17-ethynyl-1,3,5(10)-estratrien-17 beta-o1] by female rat liver enzymes.
Hepatic microsomes from female rats fed a thiamin deficient diet for three weeks had approximately three times the capacity to metabolize mestranol as microsomes from similar rats fed a diet rich in thiamin. The incremental addition of thiamin to the diet depressed mestranol O-demethylation, NADPH cytochrome c reductase, and cytochrome P-450 content in a dose related manner up to 2 microgram thiamin per gram of feed. Pair-feeding experiments indicate that thiamin ingestion is responsible for the depression of mestranol O-demethylation and NADPH cytochrome c reductase activity while carbodhydrate ingestion is responsible for the decrease in cytochrome P-450. The absorbance spectra generated by the binding of ethylisocyanide to microsomes yield data which suggest that there are no qualitative alterations in cytochrome P-450 due to diet.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008656:Mestranol / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D013832:Thiamine Deficiency / Q000201:enzymology*
D003577:Cytochrome P-450 Enzyme System; D008656:Mestranol; D010088:Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase