A Preliminary Study on The Effect of Citrus Species on Hepatic CYP1A1 Activity


Gokkaya İ., Kocyigit A., Guven N. M., Renda G., Eke B.

14th International Symposium on Pharmaceutical Sciences (ISOPS), Ankara, Turkey, 25 - 28 June 2024, pp.317

  • Publication Type: Conference Paper / Summary Text
  • City: Ankara
  • Country: Turkey
  • Page Numbers: pp.317
  • Karadeniz Technical University Affiliated: Yes

Abstract

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.