Is it possible to change milk secretion of drugs with soy enriched diets in lactating ruminants?

Soy is the most commonly used protein supplement in beef and dairy diets. Soy, which is also used as a common protein source in animal feed, is palatable and has a good amino acid balance and high bioavailability. In vivo and in vitro interaction of flavonoids, including isoflavones such as genistein and daidzein, with several ABC transporters, including breast cancer resistance protein (BCRP/ABCG2), has been demonstrated. BCRP presence in ruminants could affect the efflux of hydrophobic toxins and drugs, including their active secretion to milk and a reduction in the withdrawal time of the drug milk residues. As a result of inhibition of efflux transporters such as BCRP, changes in drug pharmacokinetics and drug transfer into milk have been observed. In this respect, the use of forage supplemented with BCRP inhibitors may be beneficial to control drug accumulation in milk and prevent undesirable contamination of milk. It is aimed to reduce the drug withdrawal periods for dairy animals with the procedure in question. In this review, it is aimed to give information about the importance of soy-enriched diets in the nutrition of ruminants during the lactation period and the effect of transport proteins on the transfer of drugs into milk.

Keywords:

BCRP/ABCG2, pharmacokinetics, soy, withdrawal time ruminat,

PDF

___

• Agatonovic-Kustrin, S., Ling, L. H., Tham, S. Y., & Alany, R. G. (2002). Molecular descriptors that influence the amount of drugs transfer into human breast milk. Journal of Pharmaceutical and Biomedical Analysis, 29(1-2), 103-119.
• Akiyama, T., Ishida, J., Nakagawa, S., Ogawara, H., Watanabe, S. I., Itoh, N. & Fukami, Y. (1987). Genistein, a specific inhibitor of tyrosine-specific protein kinases. Journal of Biological Chemistry, 262(12), 5592-5595.
• Alcorn, J., Lu, X., Moscow, J. A. & McNamara, P. J. (2002). Transporter gene expression in lactating and nonlactating human mammary epithelial cells using realtime reverse transcription-polymerase chain reaction. Journal of Pharmacology and Experimental Therapeutics, 303(2), 487-496.
• Alvarez, A. I., Merino, G., Molina, A. J., Pulido, M. M., McKellar, Q. A. & Prieto, J. G. (2006). Role of ABC transporters in veterinary drug research and parasite resistance. Current Drug Delivery, 3(2), 199-206.
• Alvarez, A. I., Vallejo, F., Barrera, B., Merino, G., Prieto, J. G., Tomas- Barberan, F. & Espin J. C. (2011). Bioavailability of the glucuronide and sulfate conjugates of genistein and daidzein in breast cancer resistance protein 1 knockout mice. Drug Metabolism and Disposition, 39, 2008–2012.
• Antignac, J. P., Cariou, R., Le Bizec, B., Cravedi, J. P. & Andre, F. (2003) Identification of phytoestrogens in bovine milk using liquid chromatography/electrospray tandem mass spectrometry. Rapid Communication in Mass Spectrometry, 17, 1256–1264.
• Ballent, M., Lifschitz, A., Virkel, G., Sallovitz, J., Maté, L. & Lanusse, C. (2012). In vivo and ex vivo assessment of the interaction between ivermectin and danofloxacin in sheep. The Veterinary Journal, 192(3), 422-427.
• Barker, S. A. & Kappel, L. C. (1997). Drug residues in milk from cows administered fenbendazole as a paste, drench, or feed top‐dressing. Journal of Veterinary Pharmacology and Therapeutics, 20(2), 160-162.
• Barnes, S. (2010). The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. Lymphatic Research and Biology, 8(1), 89-98.
• Behnke, J. M., Buttle, D. J., Stepek, G., Lowe, A. & Duce, I. R. (2008). Developing novel anthelmintics from plant cysteine proteinases. Parasites &Vectors, 1(1), 29.
• Bircsak, K. & Aleksunes, L. (2015). Interaction of isoflavones with the bcrp/abcg2 drug transporter. Current Drug Metabolism, 16(2), 124-140.
• Breedveld, P., Zelcer, N., Pluim, D., Sönmezer, Ö., Tibben, M. M., Beijnen, J. H & Schellens, J. H. (2004). Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions. Cancer Research, 64(16), 5804-5811.
• Broderick, G. A. (1995). Desirable characteristics of forage legumes for improving protein utilization in ruminants. Journal of Animal Science, 73(9), 2760-2773.
• Broderick, G. A. (2003). Effects of varying dietary protein and energy levels on the production of lactating dairy cows. Journal of Dairy Science, 86(4), 1370-1381.
• Burdette, C. Q. ve Marcus, R. K. (2013). Determination of isoflavone content in soy, red clover, and kudzu dietary supplement materials by liquid chromatography particle beam/electron ionization mass spectrometry. Journal of AOAC International, 96(5), 925-932.
• Cooray, H. C., Janvilisri, T., van Veen, H. W., Hladky, S. B. & Barrand, M. A. (2004). Interaction of the breast cancer resistance protein with plant polyphenols. Biochemical and Biophysical Research Communications, 317(1), 269-275.
• Day, A. J., DuPont, M. S., Ridley, S., Rhodes, M., Rhodes, M. J., Morgan, M. R. & Williamson, G. (1998). Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver β‐glucosidase activity. FEBS Letters, 436(1), 71-75.
• De Liguoro, M., Longo, F., Brambilla, G., Cinquina, A., Bocca, A. & Lucisano, A. (1996). Distribution of the anthelmintic drug albendazole and its major metabolites in ovine milk and milk products after a single oral dose. Journal of Dairy Research, 63(4), 533-542.
• Dupuy, J., Larrieu, G., Sutra, J. F., Lespine, A. & Alvinerie, M. (2003). Enhancement of moxidectin bioavailability in lamb by a natural flavonoid: quercetin. Veterinary Parasitology, 112(4), 337-347.
• EMA (1999). Council Regulation of the European Union No. 2377/90 and Commission Regulation Nos. 508/1999, 2385/1999, 2393/1999 and 807/2001. https://ec.europa.eu/health/sites/default/files/files/eudralex/vol5/reg_1990_2377_cons_2008/reg_1990_2377_consol_en.pdf
• Garcia-Lino, A. M., Alvarez-Fernandez, I., Blanco-Paniagua, E., Merino, G., & Alvarez, A. I. (2019). Transporters in the Mammary gland-Contribution to presence of nutrients and drugs into milk. Nutrients, 11(10), 2372.
• Henrich, C. J., Robey, R. W., Bokesch, H. R., Bates, S. E., Shukla, S., Ambudkar, S. V. & McMahon, J. B. (2007) New inhibitors of ABCG2 identified by highthroughput screening. Molecular Cancer Therapeutics, 6, 3271–3278.
• Imai, Y., Tsukahara, S., Asada, S. & Sugimoto, Y. (2004). Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. Cancer Research, 64(12), 4346-4352.
• Imperiale, F., Lifschitz, A., Sallovitz, J., Virkel, G. & Lanusse, C. (2004). Comparative depletion of ivermectin and moxidectin milk residues in dairy sheep after oral and subcutaneous administration. Journal of Dairy Research, 71(4), 427- 433.
• Ito, S. & Alcorn, J. (2003). Xenobiotic transporter expression and function in the human mammary gland. Advanced Drug Delivery Reviews, 55(5), 653-665.
• Ito, S. & Lee, A. (2003). Drug excretion into breast milk-overview. Advanced Drug Delivery Reviews, 55(5), 617-627.
• Jonker, J. W., Merino, G., Musters, S., van Herwaarden, A. E., Bolscher, E., Wagenaar, E. & Schinkel, A. H. (2005). The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk. Nature Medicine, 11(2),127-129.
• Kunta, J. R. & Sinko, P. J. (2004). Intestinal drug transporters: in vivo function and clinical importance. Current Drug Metabolism, 5(1), 109-124.
• Kuppens, I. E., Witteveen, E. O., Jewell, R. C., Radema, S. A., Paul, E. M., Mangum, S. G., & Schellens J. H. (2007) A phase I, randomized, open-label, parallel-cohort, dose-finding study of elacridar (GF120918) and oral topotecan in cancer patients. Clinical Cancer Research, 13, 3276–3285.
• Mealey, K. L. (2012). ABCG2 transporter: therapeutic and physiologic implications in veterinary species. Journal of Veterinary Pharmacology and Therapeutics, 35(2), 105-112.
• Merino, G., Molina, A. J., Garcı́a, J. L., Pulido, M. M., Prieto, J. G. & Álvarez, A. I. (2003). Intestinal elimination of albendazole sulfoxide: pharmacokinetic effects of inhibitors. International Journal of Pharmaceutics, 263(1-2), 123-132.
• Merino, G., Jonker, J. W., Wagenaar, E., van Herwaarden, A. E. & Schinkel, A. H. (2005). The breast cancer resistance protein (BCRP/ABCG2) affects pharmacokinetics, hepatobiliary excretion, and milk secretion of the antibiotic nitrofurantoin. Molecular Pharmacology, 67(5), 1758-1764.
• Merino, G., Perez, M., Real, R., Egido, E., Prieto, J. G. & Alvarez, A. I. (2010). In vivo inhibition of BCRP/ABCG2 mediated transport of nitrofurantoin by the isoflavones genistein and daidzein: A comparative study in Bcrp1−/− Mice. Pharmaceutical Research, 27(10), 2098-2105.
• Moreno, L., Imperiale, F., Mottier, L., Alvarez, L. & Lanusse, C. (2005). Comparison of milk residue profiles after oral and subcutaneous administration of benzimidazole anthelmintics to dairy cows. Analytica Chimica Acta, 536(1-2), 91-99.
• Morito, K., Hirose, T., Kinjo, J., Hirakawa, T., Okawa, M., Nohara, T. & Masamune, Y. (2001). Interaction of phytoestrogens with estrogen receptors α and β. Biological and Pharmaceutical Bulletin, 24(4), 351-356.
• Morris, M. E. & Zhang, S. (2006). Flavonoid–drug interactions: effects of flavonoids on ABC transporters. Life Sciences, 78(18), 2116-2130.
• Perez, M., Real, R., Mendoza, G., Merino, G., Prieto, J. G. ve Alvarez, A. I. (2009). Milk secretion of nitrofurantoin, as a specific BCRP/ABCG2 substrate, in assaf sheep: modulation by isoflavones. Journal of Veterinary Pharmacology and Therapeutics, 32(5), 498-502.
• Perez, M., Otero, J. A., Barrera, B., Prieto, J. G., Merino, G. & Alvarez A. I. (2013). Inhibition of ABCG2/BCRP transporter by soy isoflavones genistein and daidzein: effect on plasma and milk levels of danofloxacin in sheep. The Veterinary Journal, 196(2), 203-208.
• Pulido, M. M., Molina, A. J., Merino, G., Mendoza, G., Prieto, J. G. & Alvarez, A. I. (2006). Interaction of enrofloxacin with breast cancer resistance protein (BCRP/ABCG2): influence of flavonoids and role in milk secretion in sheep. Journal of Veterinary Pharmacology and Therapeutics, 29(4), 279-287.
• Rolfe, B. G. (1988). Flavones and isoflavones as inducing substances of legume nodulation. BioFactors (Oxford, England), 1(1), 3-10.
• Schadewinkel‐Scherkl, A. M., Rasmussen, F., Merck, C. C., Nielsen, P. & Frey, H. H. (1993). Active transport of benzylpenicillin across the blood‐milk barrier. Pharmacology & Toxicology, 73(1), 14-19.
• Schrickx, J. A. & Fink-Gremmels, J. (2008). Implications of ABC transporters on the disposition of typical veterinary medicinal products. European Journal of Pharmacology, 585(2-3), 510-519.
• Shukla, S., Ohnuma, S. & Ambudkar, S. (2011). Improving cancer chemotherapy with modulators of ABC drug transporters. Current Drug Targets, 12(5), 621-630.
• Song, T., Barua, K., Buseman, G. & Murphy, P. A. (1998). Soy isoflavone analysis: quality control and a new internal standard. The American Journal of Clinical Nutrition, 68(6), 1474S-1479S.
• Szakacs, G., Paterson, J. K., Ludwig, J. A., Booth-Genthe, C. & Gottesman, M. M. (2006). Targeting multidrug resistance in cancer. Nature Reviews Drug Discovery, 5(3), 219-234.
• Urpi-Sarda, M., Morand, C., Besson, C., Kraft, G., Viala, D., Scalbert, A. & Manach, C. (2008). Tissue distribution of isoflavones in ewes after consumption of red clover silage. Archives of Biochemistry and Biophysics, 476, 205–210.
• USDA (2008). U.S. Department of Agriculture, Agricultural Research Service. USDA Database for the Isoflavone Content of Selected Foods. Release 2.0. Nutrient Data Laboratory; https://www.ars.usda.gov/ARSUserFiles/80400525/Data/isoflav/Isoflav_R2.pdf.
• van Herwaarden, A. E. & Schinkel, A. H. (2006). The function of breast cancer resistance protein in epithelial barriers, stem cells and milk secretion of drugs and xenotoxins. Trends in Pharmacological Sciences, 27(1), 10-16.
• Virkel, G., Ballent, M., Lanusse, C. & Lifschitz, A. (2018). Role of ABC transporters in veterinary medicine: Pharmaco-toxicological implications. Current Medicinal Chemistry, 26(7), 1251-1269.
• Walle, T., Browning, A. M., Steed, L. L., Reed, S. G. & Walle, U. K. (2005). Flavonoid glucosides are hydrolyzed and thus activated in the oral cavity in humans. The Journal of Nutrition, 135(1), 48-52.
• Yao, L. H., Jiang, Y. M., Shi, J., Tomas-Barberan, F. A., Datta, N., Singanusong, R. & Chen, S. S. (2004). Flavonoids in food and their health benefits. Plant Foods for Human Nutrition, 59(3), 113-122.
• Zhang, S. & Morris, M. E. (2003). Effects of the flavonoids biochanin A, morin, phloretin, and silymarin on P-glycoprotein-mediated transport. Journal of Pharmacology and Experimental Therapeutics, 304(3), 1258-1267.
• Zhang, S., Yang, X. & Morris, M. E. (2004a). Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport. Molecular Pharmacology, 65(5), 1208-1216.
• Zhang, S., Yang, X. & Morris, M. E. (2004b). Combined effects of multiple flavonoids on breast cancer resistance protein (ABCG2)-mediated transport. Pharmaceutical Research, 21(7), 1263-1273.
• Zhao, X. & Lacasse, P. (2008). Mammary tissue damage during bovine mastitis: Causes and control. Journal of Animal Science, 86, 57-65.