Assessent of Tonica, an aqueous herbal haematinic, in the modulation of rat hepatic microsomal CYP-mediated drug metabolizing enzymes: Implications for drug interactions
No Thumbnail Available
Date
2009-02
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Pharmacology and Toxicology
Abstract
The effects of Tonica (TN), an herbal haematinic prepared from the stem barks of Khaya senegalensis, Mitragyna stipulosa and Kigelia africana, on the activities of hepatic microsomal cytochrome P450 (CYP) enzymes were investigated in Sprague-Dawley rats. TN was administered to rats, by oral gavage, at the normal human dose (28 mg/kg/day), 10x and 20x that dose for 6 weeks. Activities of certain hepatic CYP drug-metabolizing enzymes and pentobarbital-induced sleeping time were datermined in control and TN-treated animals. There were insignificant (p>0.05) increases in the microsomal protein content (3.25-31%) at all doses of TN in a non-dose-dependent fashion. However, there was a general insignificant attenuation of NADPH cytochrome c (P450) reductase activity in TN-treated animals compared to control (8.9-26.1%). p-Nitrophenol hydroxylase (pNPH) activity was insignificantly (p>0.05) elevated (14.8-23%) in the TN-treated rats compared to control. The activities of aminopyrine-N-demethylase (AmD) and nitroanisole-O-demethylase (NOD) at the normal and 10x the normal dose of TN were not significantly different from controls, but at 20x the normal dose these enzyme activities were insignificantly (p>0.05) elevated above controls (11.7 and 39.8% for AmD and NOD, respectively). Pentobarbital-induced sleeping time in TN pre-treated animals were insignificantly (p>0.05) inhibited compared to control (3.7-9.5%). These results suggest that TN by insignificantly elevating certain CYP isozymes may have the potential of modulating the metabolism of substances other than pentobarbital. © 2009 Academic Journals Inc.
Description
Keywords
Cytochrome P450, Khaya senegalensis, Kigelia Africana, Mitragyna stipulosa, Pentobarbital