Pharmacokinetics of collagen dipeptides (Gly-Pro and Pro-Hyp) and tripeptides (Gly-Pro-Hyp) in rats.

Gly-Pro Gly-Pro-Hyp Pro-Hyp pharmacokinetics rats

Journal

Journal of food science
ISSN: 1750-3841
Titre abrégé: J Food Sci
Pays: United States
ID NLM: 0014052

Informations de publication

Date de publication:
05 Dec 2023
Historique:
revised: 25 10 2023
received: 12 09 2023
accepted: 16 11 2023
medline: 5 12 2023
pubmed: 5 12 2023
entrez: 5 12 2023
Statut: aheadofprint

Résumé

Although systemic exposure to peptides, such as Gly-Pro-Hyp, Pro-Hyp, and Gly-Pro, has been reported following administration of collagen hydrolysates from fish scale and porcine skin in vivo, the individual peptide pharmacokinetics remain unknown. We administered the three peptides individually to rats via the intravenous (5 mg/kg) and intragastric (100 mg/kg) routes and then monitored systemic exposure and urinary excretion. The peptides in biological samples were analyzed via liquid chromatography/tandem mass spectrometry. Gly-Pro-Hyp tended to exhibit higher first-pass metabolism than Pro-Hyp; the absolute oral bioavailabilities of Gly-Pro-Hyp and Pro-Hyp were 4.4% and 19.3%, respectively. Gly-Pro levels were very low in the systemic circulation. Pro-Hyp biotransformed from Gly-Pro-Hyp behaved similarly to Pro-Hyp alone when administered orally. Flip-flop kinetics (elimination rate ≫ absorption rate) were evident, probably reflecting transporter-mediated slow absorption. A double-peak phenomenon was observed for Gly-Pro-Hyp and Pro-Hyp when administered orally, and 5.9% ± 2.6% and 1.9% ± 0.3% of each dose were excreted in urine after intravenous administration, respectively. Urinary recovery of Gly-Pro was limited to 0.4% ± 0.5% of the intravenous dose. This work represents the first individual pharmacokinetics of Gly-Pro-Hyp, Pro-Hyp, and Gly-Pro in vivo.

Identifiants

pubmed: 38051020
doi: 10.1111/1750-3841.16871
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : National Research Foundation of Korea
Organisme : Ministry of Food and Drug Safety of South Korea

Informations de copyright

© 2023 Institute of Food Technologists.

Références

Abe, M., Hoshi, T., & Tajima, A. (1986). Hydrogen ion-coupled transport of D-glucose by phlorizin-sensitive sugar carrier in intestinal brush-border membranes. Biochimica et Biophysica Acta, 861, 483-488.
Aito-Inoue, M., Lackeyram, D., Fan, M. Z., Sato, K., & Mine, Y. (2007). Transport of a tripeptide, Gly-Pro-Hyp, across the porcine intestinal brush-border membrane. Journal of Peptide Science, 13, 468-474.
Garrison, K. L., Sahin, S., & Benet, L. Z. (2015). Few drugs display flip-flop pharmacokinetics and these are primarily associated with classes 3 and 4 of the BDDCS. Journal of Pharmaceutical Sciences, 104, 3229-3235.
Hironaka, T., Itokawa, S., Ogawara, K., Higaki, K., & Hironaka, T. (2009). Quantitative evaluation of PEPT1 contribution to oral absorption of cephalexin in rats. Pharmaceutical Research, 26, 40-50.
Hu, Y., Smith, D. E., Ma, K., Jappar, D., Thomas, W., & Hillgren, K. M. (2008). Targeted disruption of peptide transporter Pept1 gene in mice significantly reduces dipeptide absorption in intestine. Molecular Pharmacology, 5, 1122-1130.
Ichikawa, S., Morifuji, M., Ohara, H., Matsumoto, H., Takeuchi, Y., & Sato, K. (2010). Hydroxyproline-containing dipeptides and tripeptides quantified at high concentration in human blood after oral administration of gelatin hydrolysate. International Journal of Food Science and Nutrition, 61, 52-60.
King, C. G., Morton, L. F., Onley, D. J., Peachey, A. R., Ichinobe, T., Okumura, M., Farndale, R. W., & Barnes, M. J. (1999). Collagen platelet interaction. Gly-Pro-Hyp is uniquely specific for platelet Cp VI and mediates platelet activation by collagen. Cardiovascular Research, 41, 450-457.
Laskin, D. L., Kimura, T., Sakakibara, S., Riley, D. J., & Berg, R. A. (1986). Chemotactic activity of collagen-like polypeptides for human peripheral blood neutrophils. Journal of Leukocyte Biology, 39, 255-266.
Lee, H. J., Jang, H. L., Ahn, D. K., Kim, H. J., Jeon, H. Y., Seo, D. B., Lee, J. H., Choi, J. K., & Kang, S. S. (2019). Orally administered collagen peptide protects against UVB-induced skin aging through the absorption of dipeptide forms, Gly-Pro and Pro-Hyp. Bioscience Biotechnology and Biochemistry, 83, 1146-1156.
Moskowitz, R. W. (2000). Role of collagen hydrolysate in bone and joint disease. Seminars in Arthritis and Rheumatism, 30, 87-99.
Okawa, T., Yamaguchi, Y., Takada, S., Sakai, Y., Numata, N., Nakamura, F., Nagashima, Y., Ikezawa, Z., & Aihara, M. (2012). Oral administration of collagen tripeptide improves dryness and pruritus in the acetone-induced dry skin model. Journal of Dermatology Science, 66, 136-143.
Posada, M. M., & Smith, D. E. (2013). Relevance of PepT1 in the intestinal permeability and oral absorption of cefadroxil. Pharmaceutical Research, 30, 1017-1025.
Postlethwaite, A. E., & King, A. (1976). Collagen and collagen like peptide-induced chemotaxis of human blood monocytes. Journal of Experimental Medicine, 143, 1299-1307.
Ramshaw, J. A., Shah, N. K., & Brodsky, B. (1998). Gly-X-Y tripeptide frequencies in collagen: A context for host-guest triple-helical peptides. Journal of Structural Biology, 122, 86-91.
Sontakke, S. B., Jung, J. H., Piao, Z., & Chung, H. J. (2016). Orally available collagen tripeptide: Enzymatic stability, intestinal permeability, and absorption of Gly-Pro-Hyp and Pro-Hyp. Journal of Agricultural and Food Chemistry, 64, 7127-7133.
Taga, Y., Kusubata, M., Ogawa-Goto, K., & Hattori, S. (2014). Highly accurate quantification of hydroxyproline-containing peptides in blood using a protease digest of stable isotope-labeled collagen. Journal of Agricultural and Food Chemistry, 62, 12096-12102.
Takasugi, Y., Kawata, K., Okuda, T., Koga, Y., Mizuguchi, N., Yamanaka, S., & Watanabe, S. (2003). Strain differences to effects of aging on concentrations of amino acids in cerebrospinal fluid between Sprague Dawley rat and Wistar Kyoto rat. Experimental Animals, 52, 429-432.
Tsuruoka, N., Yamato, R., Sakai, Y., Yoshitake, Y., & Yonekura, H. (2007). Promotion by collagen tripeptide of type I collagen gene expression in human osteoblastic cells and fracture healing of rat femur. Bioscience, Biotechnology and Biochemistry, 71, 2680-2687.
Wang, C. L., Fan, Y. B., Lu, H. H., Tsai, T. H., Tsai, M. C., & Wang, H. P. (2010). Evidence of D-phenylglycine as delivering tool for improving L-DOPA absorption. Journal of Biomedical Science, 17, 71.
Watanabe-Kamiyama, M., Shimizu, M., Kamiyama, S., Taguchi, Y., Sone, H., Morimatsu, F., Shirakawa, H., Furukawa, Y., & Komai, M. (2010). Absorption and effectiveness of orally administered low molecular weight collagen hydrolysate in rats. Journal of Agricultural and Food Chemistry, 58, 835-841.
Yamamoto, S., Deguchi, K., Onuma, M., Numata, N., & Sakai, Y. (2016). Absorption and urinary excretion of peptides after collagen tripeptide ingestion in humans. Biological and Pharmaceutical Bulletin, 39, 428-434.
Yamamoto, S., Hayasaka, F., Deguchi, K., Okudera, T., Furusawa, T., & Sakai, Y. (2015). Absorption and plasma kinetics of collagen tripeptide after peroral or intraperitoneal administration in rats. Bioscience Biotechnology and Biochemistry, 79, 2026-2033.
Yazaki, M., Ito, Y., Yamada, M., Goulas, S., Teramoto, S., Nakaya, M. A., Ohno, S., & Yamaguchi, K. (2017). Oral ingestion of collagen hydrolysate leads to the transportation of highly concentrated Gly-Pro-Hyp and its hydrolyzed form of Pro-Hyp into the bloodstream and skin. Journal of Agricultural and Food Chemistry, 65, 2315-2322.

Auteurs

Jihyun Won (J)

College of Pharmacy, Chung-Ang University, Seoul, South Korea.

Juhyung Kang (J)

College of Pharmacy, Chung-Ang University, Seoul, South Korea.

Keumhan Noh (K)

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.

Hee-Chul Chung (HC)

Department of Health food R&D, Newtree Co., Ltd., Seoul, South Korea.

Wonku Kang (W)

College of Pharmacy, Chung-Ang University, Seoul, South Korea.

Classifications MeSH