Evaluation of lentinan effects on cytochrome P450 activity in rats by a cocktail method

Document Type : Original Article

Authors

1 Jinhua Polytechnic, Jinhua 321007, Zhejiang, China

2 Jinhua Central Hospital, Jinhua 321000, Zhejiang, China

3 The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China

Abstract

Objective(s): In this study, a cocktail of probe drugs was used to assess whether lentinan could influence the activities of rat enzymes CYP3A4, CYP2D6, CYP1A2, CYP2C19, and CYP2C9 in vivo.
Materials and Methods: Fourteen days after intraperitoneal injection of lentinan, rats were given an oral dose of a cocktail solution containing phenacetin, tolbutamide, omeprazole, metoprolol, and midazolam. Then, we obtained blood in specific durations for the determination of plasma concentration of the probe drugs using UPLC-MS/MS. We also evaluated the pharmacokinetic parameters using the DAS 2.0 software.
Results: We found that various concentrations of lentinan increased the activity of rat CYP1A2, CYP3A4, CYP2D6, and CYP2C19 but not CYP2C9.
Conclusion: These findings suggest that clinical application of lentinan combination with CYP3A4, CYP1A2, CYP2C19, or CYP2D6 should be given careful consideration as this may lead to herb-drug interactions and hence treatment failure.

Keywords

Main Subjects

References

1. Suga T, Shiio T, Maeda YY, and Chihara G. Antitumor activity of lentinan in murine syngeneic and autochthonous hosts and its suppressive effect on 3-methylcholanthrene-induced carcinogenesis. Cancer Res 1984; 44:5132-5137.
2. Zhang L, Ji Q, Ni ZH, and Sun J. Prohibitin induces apoptosis in BGC823 gastric cancer cells through the mitochondrial pathway. Asian Pac J Cancer Prev 2012; 13:3803-3807.
3. Fujimoto K, Tomonaga M, and Goto S. A case of recurrent ovarian cancer successfully treated with adoptive immunotherapy and lentinan. Anticancer Res 2006; 26:4015-4018.
4. Chen YW, Hu DJ, Cheong KL, Li J, Xie J, Zhao J, et al. Quality evaluation of lentinan injection produced in China. J Pharm Biomed Anal 2013; 78-79:176-182.
5. Rendic S. Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev 2002; 34:83-448.
6. Rendic S and Guengerich FP. Update information on drug metabolism systems--2009, part II: summary of information on the effects of diseases and environmental factors on human cytochrome P450 (CYP) enzymes and transporters. Curr Drug Metab 2010; 11:4-84.
7. Zhou SF, Liu JP, and Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev 2009; 41:89-295.
8. Pelkonen O, Turpeinen M, Hakkola J, Honkakoski P, Hukkanen J, and Raunio H. Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol 2008; 82:667-715.
9. Jiang K, Li K, Qin F, Lu X, and Li F. Assessment of a novel beta2-adrenoceptor agonist, trantinterol, for interference with human liver cytochrome P450 enzymes activities. Toxicol In Vitro 2011; 25:1033-1038.
10. Tanaka E, Kurata N, and Yasuhara H. How useful is the “cocktail approach” for evaluating human hepatic drug metabolizing capacity using cytochrome P450 phenotyping probes in vivo? J Clin Pharm Ther 2003; 28:157-165.
11. Xu RA, Xu ZS, Lin GY, Hu LF, Wang XQ, and Ma JS. Effect of Repeated Wuniu Early Tea Administration on the CYP450 Activity Using a Cocktail Method. Indian J Pharm Sci 2013; 75:94-98.
12. Xu RA, Xu ZS, Hu LF, Zhang CH, Pan XF, Shi DW, et al. Effects of repeated allopurinol administration on rat cytochrome P450 activity. Pharmazie 2013; 68:365-368.
13. Wang S, Dong Y, Su K, Zhang J, Wang L, Han A, et al. Effect of codeine on CYP450 isoform activity of rats. Pharm Biol 2017; 55:1223-1227.
14. Wei YL, Du HJ, Lin YP, Wu ML, Ying XQ, Ding MX, et al. Simultaneous determination of five rat CYP450 probe drugs by UPLC-MS/MS method. Latin American Journal of Pharmacy 2016; 35:1810-1815.
15. Shimada T, Yamazaki H, Mimura M, Inui Y, and Guengerich FP. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 1994; 270:414-423.
16. Mustajoki P, Mustajoki S, Rautio A, Arvela P, and Pelkonen O. Effects of heme arginate on cytochrome P450-mediated metabolism of drugs in patients with variegate porphyria and in healthy men. Clin Pharmacol Ther 1994; 56:9-13.
17. Miners JO and Birkett DJ. Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 1998; 45:525-538.
18. Goldstein JA and de Morais SM. Biochemistry and molecular biology of the human CYP2C subfamily. Pharmacogenetics 1994; 4:285-299.
19. Lu SK, Callahan SM, and Brunner LJ. Suppression of hepatic CYP3A1/2 and CYP2C11 by cyclosporine is not mediated by altering growth hormone levels. J Pharmacol Exp Ther 2003; 305:331-337.
20. Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet 2009; 48:689-723.
21. Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II. Clin Pharmacokinet 2009; 48:761-804.

Iranian Journal of Basic Medical Sciences
Volume 22, Issue 3
March 2019
Pages 296-301

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