Orange Juice and Its Component, Hesperidin, Decrease the Expression of Multidrug Resistance-associated Protein 2 in Rat Small Intestine and Liver

Overview

Journal J Biomed Biotechnol

Specialty Biology

Date 2011 Jun 11

PMID 21660137

Citations 1

Authors

Minoru Watanabe

Naoki Matsumoto

Yuko Takeba

Toshio Kumai

Masami Tanaka

Shinobu Tatsunami

Sachiko Takenoshita-Nakaya

Yoshie Harimoto

Yuichi Kinoshita

Shinichi Kobayashi

Affiliations

Soon will be listed here.

Abstract

We investigated the effects of orange juice (OJ) or hesperidin, a component of OJ, on the pharmacokinetics of pravastatin (PRV) and the expression of both protein and mRNA of multidrug resistance-associated protein 2 (Mrp2) in the rat small intestine and liver. Eight-week-old male Sprague-Dawley rats were used in this study. OJ or a 0.079% hesperidin suspension was administered orally for 2 days. Tap water was given as a control. A single dose of PRV at 100 mg/kg p.o. was administered after 2 days of OJ, hesperidin, or tap water ingestion. The AUC, C(max), and t(1/2) values of PRV were significantly increased in OJ group. Mrp2 protein and mRNA levels in the small intestine and liver, respectively, were significantly decreased after the ingestion of OJ. The same results were obtained with hesperidin. These results suggest that the changes in PRV pharmacokinetic parameters and the decrease in Mrp2 expression caused by OJ are due to hesperidin in the juice.

Citing Articles

Vitamin D Deficiency Impacts Exposure and Response of Pravastatin in Male Rats by Altering Hepatic OATPs.

Peng J, Yang G, Huang Z Front Pharmacol. 2022; 13:841954.

PMID: 35250587 PMC: 8892078. DOI: 10.3389/fphar.2022.841954.

References

Kivisto K, Grisk O, Hofmann U, Meissner K, Moritz K, Ritter C . Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats. Drug Metab Dispos. 2005; 33(11):1593-6. DOI: 10.1124/dmd.105.006262. View

Jacobsen W, Kirchner G, Hallensleben K, Mancinelli L, Deters M, Hackbarth I . Comparison of cytochrome P-450-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver. Drug Metab Dispos. 1999; 27(2):173-9. View

Hirano M, Maeda K, Matsushima S, Nozaki Y, Kusuhara H, Sugiyama Y . Involvement of BCRP (ABCG2) in the biliary excretion of pitavastatin. Mol Pharmacol. 2005; 68(3):800-7. DOI: 10.1124/mol.105.014019. View

Tokui T, Nakai D, Nakagomi R, Yawo H, Abe T, Sugiyama Y . Pravastatin, an HMG-CoA reductase inhibitor, is transported by rat organic anion transporting polypeptide, oatp2. Pharm Res. 1999; 16(6):904-8. DOI: 10.1023/a:1018838405987. View

Borst P, Evers R, Kool M, Wijnholds J . A family of drug transporters: the multidrug resistance-associated proteins. J Natl Cancer Inst. 2000; 92(16):1295-302. DOI: 10.1093/jnci/92.16.1295. View

Careri M, Elviri L, Mangia A, Musci M . Spectrophotometric and coulometric detection in the high-performance liquid chromatography of flavonoids and optimization of sample treatment for the determination of quercetin in orange juice. J Chromatogr A. 2000; 881(1-2):449-60. DOI: 10.1016/s0021-9673(00)00256-9. View

Otter K, Mignat C . Determination of pravastatin in human plasma by high-performance liquid chromatography with ultraviolet detection. J Chromatogr B Biomed Sci Appl. 1998; 708(1-2):235-41. DOI: 10.1016/s0378-4347(97)00625-7. View

Tian R, Koyabu N, Takanaga H, Matsuo H, Ohtani H, Sawada Y . Effects of grapefruit juice and orange juice on the intestinal efflux of P-glycoprotein substrates. Pharm Res. 2002; 19(6):802-9. DOI: 10.1023/a:1016100715125. View

Abe T, Kakyo M, Sakagami H, Tokui T, Nishio T, Tanemoto M . Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2. J Biol Chem. 1998; 273(35):22395-401. DOI: 10.1074/jbc.273.35.22395. View

10.

Yamazaki M, Akiyama S, Niinuma K, Nishigaki R, Sugiyama Y . Biliary excretion of pravastatin in rats: contribution of the excretion pathway mediated by canalicular multispecific organic anion transporter. Drug Metab Dispos. 1997; 25(10):1123-9. View

11.

Ameer B, WEINTRAUB R, Johnson J, Yost R, Rouseff R . Flavanone absorption after naringin, hesperidin, and citrus administration. Clin Pharmacol Ther. 1996; 60(1):34-40. DOI: 10.1016/S0009-9236(96)90164-2. View

12.

Dresser G, Bailey D . The effects of fruit juices on drug disposition: a new model for drug interactions. Eur J Clin Invest. 2003; 33 Suppl 2:10-6. DOI: 10.1046/j.1365-2362.33.s2.2.x. View

13.

Erlund I, Meririnne E, Alfthan G, Aro A . Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. J Nutr. 2001; 131(2):235-41. DOI: 10.1093/jn/131.2.235. View

14.

Kitaoka Y, Kumai T, Kitaoka Y, Lam T, Munemasa Y, Isenoumi K . Nuclear factor-kappa B p65 in NMDA-induced retinal neurotoxicity. Brain Res Mol Brain Res. 2004; 131(1-2):8-16. DOI: 10.1016/j.molbrainres.2004.07.021. View

15.

Hagenbuch B, Meier P . The superfamily of organic anion transporting polypeptides. Biochim Biophys Acta. 2003; 1609(1):1-18. DOI: 10.1016/s0005-2736(02)00633-8. View

16.

Tatsunami S, Ito A, Kawata K, Kuwabara R, Yamada K . Determination of pharmacokinetic parameters of stavudine in Japanese patients infected with HIV-1, using a Gaussian-like input rate function. Eur J Drug Metab Pharmacokinet. 2001; 26(1-2):137-40. DOI: 10.1007/BF03190387. View

17.

Koitabashi Y, Kumai T, Matsumoto N, Watanabe M, Sekine S, Yanagida Y . Orange juice increased the bioavailability of pravastatin, 3-hydroxy-3-methylglutaryl CoA reductase inhibitor, in rats and healthy human subjects. Life Sci. 2006; 78(24):2852-9. DOI: 10.1016/j.lfs.2005.11.006. View

18.

Iacona I, Regazzi M, Buggia I, Villani P, Fiorito V, Molinaro M . High-performance liquid chromatography determination of pravastatin in plasma. Ther Drug Monit. 1994; 16(2):191-5. DOI: 10.1097/00007691-199404000-00014. View

19.

Ito K, Suzuki H, Hirohashi T, Kume K, Shimizu T, Sugiyama Y . Molecular cloning of canalicular multispecific organic anion transporter defective in EHBR. Am J Physiol. 1997; 272(1 Pt 1):G16-22. DOI: 10.1152/ajpgi.1997.272.1.G16. View

20.

Komai T, Kawai K, Tokui T, Tokui Y, Kuroiwa C, Shigehara E . Disposition and metabolism of pravastatin sodium in rats, dogs and monkeys. Eur J Drug Metab Pharmacokinet. 1992; 17(2):103-13. DOI: 10.1007/BF03188778. View