Metabolism of camphors and related compounds

Abstract

1. The metabolism of (+/-)-norcamphor, (+)-camphor, (-)-camphor, (+)-epicamphor, (+/-)-camphorquinone, (+/-)-camphane-2,5-dione and camphane was investigated in rabbits. All the compounds except camphane-2,5-dione increased the content of glucuronide in the urine. 2. (+/-)-Norcamphor was reduced to endo-norborneol; (+)-camphor, contrary to expectation, was reduced to (+)-borneol, as well as being hydroxylated to (+)-5-endo-hydroxycamphor and (+)-3-endo-hydroxycamphor, 5-endo-hydroxycamphor being the predominant product. (+)-Epicamphor was reduced mainly to (+)-epiborneol; (+/-)-camphorquinone gave 3-endo-hydroxycamphor and 2-endo-hydroxyepicamphor, the former being the major metabolite. (+/-)-Camphane-2,5-dione was reduced to 5-endo-hydroxycamphor. Camphane was hydroxylated to borneol and epiborneol, the latter predominating. 3. An explanation of these findings is given in terms of steric hindrance and thermodynamic stability. 4. The possibility was investigated that NADH was involved in the reductions.

Camphor: risks and benefits of a widely used natural product

“…Asahina and Ishidate (1933;1934;1935) isolated cis-and trans-π-hydroxycamphor and camphor-π-carboxylic acid from the urine of dogs that had been fed with camphor; Shimamoto obtained 3-hydroxycamphor (15%), 5-hydroxycamphor (55%) and trans-π-hydroxycamphor (20%) from the urine of dogs, and 5-hydroxycamphor [as major metabolite] and 3-hydroxycamphor from the urine of rabbits (Shimamoto, 1934). Robertson and Hussain (1969) observed that (+)-camphor and (-)-camphor increase the content of glucuronide in the urine of rabbits; (+)-camphor was moreover reduced to (+)-borneol as well as being hydroxylated to (+)-5-endo-hydroxycamphor [major product] and (+)-3-endo-hydroxycamphor. Hydroxylation of camphor, as well as norcamphor, pericyclocamphanone and 5,5-difluorocamphor, is mainly performed by Cytochrome P-450 (Collins and Loew, 1988), a class of heme-containing monooxygenases that are distributed in the whole body (Boxenbaum, 1984), by hydrogen abstraction (Wand and Thompson, 1986).…”

In Vitro Metabolism of (-)-Camphor Using Human Liver Microsomes and CYP2A6

“…Metabolites in rabbit liver microsomes were similar to those obtained in the analogous rat liver microsomes, except that the ratio of endo-and exo-isomers of 5-hydroxycamphor produced from camphor was higher than in the rat liver preparation. 3,4) In human liver microsomes, 5-exo-hydroxycamphor was detected only an oxidation product. These results suggested that there are species-related differences in the metabolism of camphor to 3-hydroxycamphor, 5-exo-and 5-endo-hydroxycamphor by P450 enzymes in rats, rabbits and humans.…”

“…Metabolism of (Ϫ)-camphor in mammals, microorganism and plant cells have been published, e.g. dogs, 3,4) rabbits, 4) Pseudomonas putida, [5][6][7][8][9][10][11] Streptomyces griseus 12) the S. officinals [13][14][15] and Eucalyptus perriniana. 16) We recently established the biotransformation of (ϩ)-and (Ϫ)-camphor by Spodoptera litura (a species of caterpillar).…”

Scientific Opinion on Flavouring Group Evaluation 47, Revision 1 (FGE.47Rev1): Bi‐ and tricyclic secondary alcohols, ketones and related esters from chemical group 8

“…Rabbits gavaged with 1.9 -3.5 mmol/kg bw [289 -533 mg/kg bw] d-camphor excreted 59.1 % of the dose conjugated with glucuronic acid in the urine within 24 hours (Robertson and Hussain, 1969). A group of 50 Sprague-Dawley rats was administered a single dose of 1,000 mg of 40 % camphor in cottonseed oil/kg bw (approximately 400 mg camphor) by gavage and killed at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 or 10.0 hours following treatment.…”