Studies on the metabolism of l-menthol in rats.

Abstract

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)

• Authors: K M Madyastha, V Srivatsan
• Journal: Drug metabolism and disposition: the biological fate of chemicals (Drug Metab Dispos) 1988 Sep-Oct Vol. 16 Issue 5 Pg. 765-72 ISSN: 0090-9556 [Print] United States
• PMID: 2906604 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytochrome b Group
• Menthol
• Cytochromes b5
• Cytochrome P-450 Enzyme System
• NADPH-Ferrihemoprotein Reductase
• NADH Dehydrogenase

Topics

• Animals
• Biotransformation
• Chromatography, Gas
• Cytochrome P-450 Enzyme System (biosynthesis)
• Cytochrome b Group (biosynthesis)
• Cytochromes b5
• Magnetic Resonance Spectroscopy
• Male
• Mass Spectrometry
• Menthol (metabolism, pharmacology, urine)
• Microsomes, Liver (drug effects, metabolism)
• NADH Dehydrogenase (biosynthesis)
• NADPH-Ferrihemoprotein Reductase (biosynthesis)
• Rats
• Rats, Inbred Strains
• Reference Values