Akademik Veri Yönetim Sistemi
14th International Symposium on Pharmaceutical Sciences (ISOPS), Ankara, Türkiye, 25 - 28 Haziran 2024, ss.317
Introduction: The simultaneous use of herbal
products with medicines increases the risk of interactions. Citrus fruit
juices are one of the most widely consumed herbal products worldwide. Cytochrome
P450 (CYP450) enzymes, which are important for xenobiotic and drug metabolism,
are found in organs like the liver. CYP1A1 is an important isozyme involved in
the metabolism of many drugs, such as caffeine, theophylline, paracetamol,
riociguat, granisetron, axitinib, erlotinib, and conivaptan. Previous studies
have reported that the juices of some Citrus species mainly grapefruit, cause
drug interactions through modulation of CYP450 enzymes (1, 2). Upon
review of the literature, there are a limited number of studies evaluating the
efficacy of Citrus species on CYP1A1-mediated metabolism. This study
aimed to investigate the effects of Citrus fruit juices on
CYP1A1 activity.
Materials and Methods: The effects of 5 mg/mL doses of Citrus
fruit juices on CYP1A1 enzyme activities in rat hepatic microsomes were
investigated using the 7-ethoxyresorufin O-deethylase
(EROD) assay. EROD activity is measured by following the CYP1A1-mediated
deethylation of the substrate 7-ethoxyresorufin to form the product resorufin,
which can be monitored fluorometrically. While caffeine was employed as a
standard, the control used in this protocol was dimethyl sulfoxide (DMSO) in
which the synthesized compounds were dissolved.
Results: Citrus
sinensis (L.) Osbeck, Citrus japonica Thunb., and Citrus
australasica F.Muell. fruit juices were found to inhibit CYP1A1 activity by
50%, 50%, and 60%, respectively (caffeine: 56%).
Conclusions: In
this study, some Citrus species were predicted to affect CYP1A1
activity. The simultaneous use of C. sinensis, C. japonica, and C.
australasica fruit juices with drugs metabolized by the CYP 1A1 isozyme
should be monitored carefully.