Studies on the metabolism of l-menthol in rats.
Metabolism of l-menthol in rats was investigated both in vivo and in vitro. Metabolites isolated and characterized from the urine of rats after oral administration (800 mg/kg of body weight/day) of l-menthol were the following: p-menthane-3,8-diol (II), p-menthane-3,9-diol (III), 3,8-oxy-p-menthane-7-carboxylic acid (IV), and 3,8-dihyroxy-p-menthane-7-carboxylic acid (V). In vivo, the major urinary metabolites were compounds II and V. Repeated oral administration (800 mg/kg of body weight/day) of l-menthol to rats for 3 days resulted in the increase of both liver microsomal cytochrome P-450 content and NADPH-cytochrome c reductase activity by nearly 80%. Further treatment (for 7 days total) reduced their levels considerably, although the levels were still higher than the control values. Both cytochrome b5 and NADH-cytochrome c reductase levels were not changed during the 7 days of treatment. Rat liver microsomes readily converted l-menthol to p-menthane-3,8-diol (II) in the presence of NADPH and O2. This activity was significantly higher in microsomes obtained from phenobarbital (PB)-induced rats than from control microsomal preparations, whereas 3-methylcholanthrene (3-MC)-induced microsomes failed to convert l-menthol to compound II in the presence of NADPH and O2. l-Menthol elicited a type I spectrum with control (Ks = 60.6 microM) and PB-induced (Ks = 32.3 microM) microsomes whereas with 3MC-induced microsomes it produced a reverse type I spectrum.(ABSTRACT TRUNCATED AT 250 WORDS)
Madyastha
K M
KM
Department of Organic Chemistry, Indian Institute of Science, Bangalore.
Srivatsan
V
V
D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003573:Cytochrome b Group / Q000096:biosynthesis; D015786:Cytochromes b5; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008610:Menthol / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000096:biosynthesis; D009251:NADPH-Ferrihemoprotein Reductase / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D003573:Cytochrome b Group; D008610:Menthol; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; D009245:NADH Dehydrogenase