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Toxicity of a 90-day repeated oral dose of a collagen peptide derived from skate (Raja kenojei) skin: a rat model study

  • Heung-Sik Seo (Health Care Institute, Korea Testing and Research Institute) ;
  • Jun-Ho Kim (Health Care Institute, Korea Testing and Research Institute) ;
  • Sang-Ho Kim (Health Care Institute, Korea Testing and Research Institute) ;
  • Myeong-Kyu Park (Health Care Institute, Korea Testing and Research Institute) ;
  • Nak-Won Seong (Health Care Institute, Korea Testing and Research Institute) ;
  • Geun-Hee Kang (Yeongsan Skate Co., Ltd) ;
  • Joong-Sun Kim (College of Veterinary Medicine, Chonnam National University) ;
  • Sung-Ho Kim (College of Veterinary Medicine, Chonnam National University) ;
  • Jong-Choon Kim (College of Veterinary Medicine, Chonnam National University) ;
  • Changjong Moon (College of Veterinary Medicine, Chonnam National University)
  • Received : 2022.12.19
  • Accepted : 2023.03.02
  • Published : 2023.07.15

Abstract

Collagen peptides are widely employed as therapeutic materials due to their numerous beneficial properties, including for the following uses: antiaging, antioxidant applications, antibacterial applications, wound healing, tissue engineering, medication delivery, and cosmetics. Although collagen peptides are useful in these applications, to our knowledge, few published studies have been undertaken on their repeated-dose toxicity. We evaluated the possible subchronic toxicity of a collagen peptide derived from skate (Raja kenojei) skin (CPSS) in Sprague-Dawley rats by administering repeated oral doses over 90 days. Rats of both sexes were assigned randomly to one of four experimental groups, respectively receiving 0, 500, 1000, or 2000 mg/kg/day of CPSS. At all doses tested, repeated oral CPSS administration had no treatment-related adverse effects in terms of clinical signs, body weight, food consumption, detailed clinical observation, sensory reactivity, functional assessment, urinalysis, ophthalmic examination, gross pathology, hematology, serum biochemistry, hormone analysis, organ weight, and histopathology. Even though there were some alterations in hematologic parameters, serum biochemistry parameters, organ weight, and histopathological findings, these did not follow a dose-response pattern and were within historical limits for control rats. The oral no-observed-adverse-effect level (NOAEL) of the CPSS was 2000 mg/kg/day for both male and female rats in the applied experimental circumstances, and no target organs were identified.

Keywords

Acknowledgement

This study was supported by a grant from the Support for Development and Commercialization of Marine Bio-Strategic Materials Project (Project Number: 20200329), Korea Institute of Marine Science and Technology Promotion, Korea.

References

  1. Kuzan A, Smulczynska-Demel A, Chwilkowska A, Saczko J, Frydrychowski A, Dominiak M (2015) An estimation of the biological properties of fish collagen in an experimental in vitro study. Adv Clin Exp Med 24:385-392. https://doi.org/10.17219/acem/31704
  2. Wang L, An X, Yang F, Xin Z, Zhao L, Hu Q (2008) Isolation and characterization of collagens from the skin, scale and bone of deep-sea redfish (Sebastes mentella). Food Chem 108:616-623. https://doi.org/10.1016/j.foodchem.2007.11.017
  3. Wang Z, Wang Q, Wang L, Xu W, He Y, Li Y, He S, Ma H (2017) Improvement of skin condition by oral administration of collagen hydrolysates in chronologically aged mice. J Sci Food Agric 97:2721-2726. https://doi.org/10.1002/jsfa.8098
  4. Tanaka M, Koyama Y, Nomura Y (2009) Effects of collagen peptide ingestion on UV-B-induced skin damage. Biosci Biotechnol Biochem 73:930-932. https://doi.org/10.1271/bbb.80649
  5. Felician FF, Xia C, Qi W, Xu H (2018) Collagen from marine biological sources and medical applications. Chem Biodivers 15:e1700557. https://doi.org/10.1002/cbdv.201700557
  6. Ricard-Blum S (2011) The collagen family. Cold Spring Harb Perspect Biol 3:a004978. https://doi.org/10.1101/cshperspect.a004978
  7. Wisniewski K, Artemowicz B, Lutostanska A, Mackowiak J, Koziolkiewicz W (1994) Central activity of peptide gly-pro-hyp-the main component of collagen degradation products mixture. Acta Neurobiol Exp (Wars) 54:33-38. https://pubmed.ncbi.nlm.nih.gov/8023712/ https://doi.org/10.55782/ane-1994-999
  8. Ohara H, Ichikawa S, Matsumoto H, Akiyama M, Fujimoto N, Kobayashi T, Tajima S (2010) Collagen-derived dipeptide, proline-hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts. J Dermatol 37:330-338. https://doi.org/10.1111/j.1346-8138.2010.00827.x
  9. Sontakke SB, Jung JH, Piao Z, Chung HJ (2016) Orally available collagen tripeptide: enzymatic stability, intestinal permeability, and absorption of gly-pro-hyp and pro-hyp. J Agric Food Chem 64:7127-7133. https://doi.org/10.1021/acs.jafc.6b02955
  10. Hartmann R, Meisel H (2007) Food-derived peptides with biological activity: from research to food applications. Curr Opin Biotechnol 18:163-169. https://doi.org/10.1016/j.copbio.2007.01.013
  11. Yang H, Wang H, Zhao Y, Wang H, Zhang H (2015) Effect of heat treatment on the enzymatic stability of grass carp skin collagen and its ability to form fibrils in vitro. J Sci Food Agric 95:329-336. https://doi.org/10.1002/jsfa.6724
  12. Woo M, Noh JS (2020) Regulatory effects of skate skin-derived collagen peptides with different molecular weights on lipid metabolism in the liver and adipose tissue. Biomedicines 8:187. https://doi.org/10.3390/biomedicines8070187
  13. Woo M, Seol BG, Kang KH, Choi YH, Cho EJ, Noh JS (2020) Effects of collagen peptides from skate (Raja kenojei) skin on improvements of the insulin signaling pathway via attenuation of oxidative stress and inflammation. Food Funct 11:2017-2025. https://doi.org/10.1039/c9fo02667c
  14. Tak YJ, Kim YJ, Lee JG, Yi YH, Cho YH, Kang GH, Lee SY (2019) Effect of oral ingestion of low-molecular collagen peptides derived from skate (Raja kenojei) skin on body fat in overweight adults: a randomized, double-blind, placebo-controlled trial. Mar Drugs 17:157. https://doi.org/10.3390/md17030157
  15. De Luca C, Mikhal'chik EV, Suprun MV, Papacharalambous M, Truhanov AI, Korkina LG (2016) Skin antiageing and systemic redox effects of supplementation with marine collagen peptides and plant-derived antioxidants: A single-blind case-control clinical study. Oxid. Med. Cell. Longev, 2016, 4389410. https://doi.org/10.1155/2016/4389410
  16. Pozzolini M, Millo E, Oliveri C, Mirata S, Salis A, Damonte G, Arkel M, Scarfi S (2018) Elicited ROS scavenging activity, photoprotective, and wound-healing properties of collagen-derived peptides from the marine sponge Chondrosia reniformis. Mar Drugs 16:465. https://doi.org/10.3390/md16120465
  17. Peng X, Xu J, Tian Y, Liu W, Peng B (2020) Marine fish peptides (collagen peptides) compound intake promotes wound healing in rats after cesarean section. Food Nutr Res 64:4247. https://doi.org/10.29219/fnr.v64.4247
  18. Cheng X, Shao Z, Li C, Yu L, Raja MA, Liu C (2017) Isolation, characterization and evaluation of collagen from jellyfish Rhopilema esculentum kishinouye for use in hemostatic applications. PLoS One 12:e0169731. https://doi.org/10.1371/journal.pone.0169731
  19. Vigneswari S, Gurusamy TP, Khalil A, Ramakrishna HPS, Amirul S, A. A (2020) Elucidation of antimicrobial silver sulfadiazine (SSD) blend/poly(3-Hydroxybutyrate-co-4-Hydroxybutyrate) immobilised with collagen peptide as potential biomaterial. Polym (Basel) 12:2979. https://doi.org/10.3390/polym12122979
  20. Venkatesan J, Anil S, Kim SK, Shim MS (2017) Marine fish proteins and peptides for cosmeceuticals: a review. Mar Drugs 15:143. https://doi.org/10.3390/md15050143
  21. Wu J, Fujioka M, Sugimoto K, Mu G, Ishimi Y (2004) Assessment of effectiveness of oral administration of collagen peptide on bone metabolism in growing and mature rats. J Bone Miner Metab 22:547-553. https://doi.org/10.1007/s00774-004-0522-2
  22. Liang J, Pei XR, Zhang ZF, Wang N, Wang JB, Li Y (2012) A chronic oral toxicity study of marine collagen peptides preparation from chum salmon (Oncorhynchus keta) skin using Sprague-Dawley rat. Mar Drugs 10:20-34. https://doi.org/10.3390/md10010020
  23. Moskowitz RW (2000) Role of collagen hydrolysate in bone and joint disease. Semin Arthritis Rheum 30:87-99. https://doi.org/10.1053/sarh.2000.9622
  24. Han ZZ, Xu HD, Kim KH, Ahn TH, Bae JS, Lee JY, Gil KH, Lee JY, Woo SJ, Yoo HJ, Lee HK, Kim KH, Park CK, Zhang HS, Song SW (2010) Reference data of the main physiological parameters in control Sprague-Dawley rats from pre-clinical toxicity studies. Lab Anim Res 26:153-164. https://doi.org/10.5625/lar.2010.26.2.153
  25. Lee JM, Lee MA, Do HN, Song YI, Bae RJ, Lee HY, Park SH, Kang JS, Kang JK (2012) Historical control data from 13-week repeated toxicity studies in Crj:CD (SD) rats. Lab Anim Res 28:115-121. https://doi.org/10.5625/lar.2012.28.2.115
  26. Greaves P (2012) Histopathology of preclinical toxicity studies. Interpretation and relevance in Drug Safety evaluation, 4th edn. Elesevier, New York
  27. Haschek WM, Wallig M, Rousseaux CG (2009) Fundamentals of toxicologic pathology, 2nd edn. Academic Press, San Diego
  28. Yang YS, Lee SB, Choi SJ, Lee BS, Heo JD, Song CW, Kim HY, Kim JC, Lee K (2014) Evaluation of subchronic inhalation toxicity of methylcyclopentane in rats. Food Chem Toxicol 63:186-194. https://doi.org/10.1016/j.fct.2013.11.001
  29. Seong NW, Seo HS, Kim JH, Kim YJ, Kim E, Lee JY, Ko JW, Kim JC (2018) A 13-week subchronic toxicity study of an Eriobotrya japonica leaf extract in rats. J Ethnopharmacol 226:1-10. https://doi.org/10.1016/j.jep.2018.07.024