Effects of capsaicinoids on oxidative metabolism of caffeine in isolated rat hepatocytes

• Published in: European journal of drug metabolism and pharmacokinetics Vol. 20; no. 3; p. 179
• Main Authors: Bouraoui, A, Brazier, J L, Zouaghi, H, Ribon, B, Vermeulen, E, Desage, M
• Format: Journal Article
• Language: English
• Published: France 01.07.1995
• Subjects: Animals; Caffeine - metabolism; Capsaicin - pharmacology; Central Nervous System Stimulants - metabolism; Liver - metabolism; Male; Microsomes, Liver - metabolism; Oxidation-Reduction; Rats; Rats, Wistar; Xanthines - metabolism
• ISSN: 0378-7966; 2107-0180
• DOI: 10.1007/BF03189667

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.