title: Effects of capsaicinoids on oxidative metabolism of caffeine in isolated rat hepatocytes.
abstract: The metabolism of caffeine was studied in isolated rat hepatocytes, in the absence and presence of capsaicinoids. Caffeine and four primary metabolite fractions were identified by high performance liquid chromatography: 1,7-dimethylxanthine, 3,7-dimethylxanthine, 1,3-dimethylxanthine and 1,3,7-trimethyluric acid. The incubation with the lowest concentrations (0.1 and 1 microM) of capsaicinoids (natural extract, capsaicin, dihydrocapsaicin) showed a stimulatory effect on caffeine metabolism, which was further enhanced with capsaicin. At 10 microM, capsaicin stimulated the two pathways of metabolism of caffeine (N-demethylation and C-8 oxidation). In contrast, dihydrocapsaicin and the natural extract seem to inhibit the N-demethylation pathways without affecting the C-8 oxidation route. The inhibitory activity on the N-demethylation pathways and especially the N-7 demethylation pathway was pronounced at the first 30 min of incubation. These results suggest that the two pathways (N-demethylation and C-8 oxidation) are mediated by different isozymes of cytochromes P-450. This is in agreement with recent findings.
authors: Laboratoire de Pharmacologie, Faculté de Pharmacie, Monastir, Tunisia.
authors: A
authors: A
authors: Bouraoui
authors: J L
authors: JL
authors: Brazier
authors: H
authors: H
authors: Zouaghi
authors: B
authors: B
authors: Ribon
authors: E
authors: E
authors: Vermeulen
authors: M
authors: M
authors: Desage
mesh_terms: D000818:Animals; D002110:Caffeine / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D014970:Xanthines / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D014970:Xanthines; C008514:methylxanthine; D002110:Caffeine; D002211:Capsaicin