Abstract
Background
The medicinal properties and benefits of collagen peptides (CPs) are widely recognized and utilized. However, the potential genotoxicity of CPs remains elusive.
Objective
The objective of this study was to assess the potential genotoxicity of CP derived from skate (Raja kenojei) skin (CPSS). To achieve this, we conducted a comprehensive study using three standard battery systems in accordance with the test guidelines provided by the Organisation for Economic Cooperation and Development and the Korean Ministry of Food and Drug Safety, as well as the principles of Good Laboratory Practice.
Results
We performed a bacterial reverse mutation (Ames) test using the pre-incubation method, with or without a metabolic activation system (S9 mixture). The Ames test, conducted on Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, as well as Escherichia coli strain WP2uvrA, demonstrated that CPSS did not cause gene mutations in any of the tested strains, regardless of the dose level. In addition, we performed an in vitro chromosome aberration test using cultured Chinese hamster lung fibroblast cells, with and without the S9 mixture, and an in vivo mouse bone marrow micronucleus test on specific pathogen-free male ICR mice. Both the in vitro chromosomal aberration test and the in vivo micronucleus test revealed no chromosomal aberrations resulting from CPSS treatment.
Conclusion
Our findings demonstrate that CPSS does not exhibit mutagenic or clastogenic activity in either in vitro or in vivo test systems, supporting its potential as a safe material for medical use.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Cha SB et al (2021) Evaluation of the in vitro and in vivo genotoxicity of a Dioscorea Rhizome water extract. Toxicol Res 37:385–393
Chen Q et al (2009) Investigation of the genotoxicity of quinocetone, carbadox and olaquindox in vitro using Vero cells. Food Chem Toxicol 47:328–334
Cheng X et al (2017) Isolation, Characterization and Evaluation of Collagen from Jellyfish Rhopilema esculentum Kishinouye for Use in Hemostatic Applications. PLoS ONE 12:e0169731
De Luca C et al (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
Felician FF, Xia C, Qi W, Xu H (2018) Collagen from Marine Biological Sources and Medical Applications. Chem Biodivers 15:e1700557
Japanese Environmental Mutagen Society MMSG (1988) The atlas of chromosomal aberrations induced by chemicals. Asakura-Shoten, Tokyo
Kim JY, Ri Y, Do SG, Lee YC, Park SJ (2014) Evaluation of the genotoxicity of ginseng leaf extract UG0712. Lab Anim Res 30:104–111
Kirsch-Volders M et al (2003) Report from the in vitro micronucleus assay working group. Mutat Res 540:153–163
Kuzan A et al (2015) An Estimation of the Biological Properties of Fish Collagen in an Experimental In Vitro Study. Adv Clin Exp Med 24:385–392
Mortelmans K, Zeiger E (2000) The Ames Salmonella/microsome mutagenicity assay. Mutat Res 455:29–60
OECD (2016b) Test No. 474: Mammalian Erythrocyte Micronucleus Test. https://doi.org/10.1787/9789264264762-en
OECD (2016a) Test No. 473: In Vitro Mammalian Chromosomal Aberration Test. https://doi.org/10.1787/9789264264649-en
OECD (2020) Test No. 471: Bacterial Reverse Mutation Test. https://doi.org/10.1787/9789264071247-en
Ohara H et al (2010) Collagen-derived dipeptide, proline-hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts. J Dermatol 37:330–338
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
Phillips DH, Arlt VM (2009) Genotoxicity: damage to DNA and its consequences. EXS 99:87–110
Postlethwaite AE, Seyer JM, Kang AH (1978) Chemotactic attraction of human fibroblasts to type I, II, and III collagens and collagen-derived peptides. Proc Natl Acad Sci U S A 75:871–875
Pozzolini M et al (2018) Elicited ROS Scavenging Activity, Photoprotective, and Wound-Healing Properties of Collagen-Derived Peptides from the Marine Sponge Chondrosia reniformis. Mar Drugs 16:465
Rajanbabu V, Chen JY (2011) Applications of antimicrobial peptides from fish and perspectives for the future. Peptides 32:415–420
Seo HS et al (2023) Toxicity of a 90-day repeated oral dose of a collagen peptide derived from skate (Raja kenojei) skin: a rat model study. Toxicol Res 39:383–398
Sorushanova A et al (2019) The Collagen Suprafamily: From Biosynthesis to Advanced Biomaterial Development. Adv Mater 31:e1801651
Tak YJ et al (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
Venkatesan J, Anil S, Kim SK, Shim MS (2017) Marine Fish Proteins and Peptides for Cosmeceuticals: A Review. Mar Drugs 15:143
Vigneswari S, Gurusamy TP, Khalil HPSA, Ramakrishna S, Amirul AA (2020) Elucidation of Antimicrobial Silver Sulfadiazine (SSD) Blend/Poly(3-Hydroxybutyrate–4-Hydroxybutyrate) Immobilised with Collagen Peptide as Potential Biomaterial. Polymers-Basel 12:2979
Wang Z et al (2017) Improvement of skin condition by oral administration of collagen hydrolysates in chronologically aged mice. J Sci Food Agric 97:2721–2726
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
Woo M et al (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
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
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
Yun JW et al (2017) Evaluation of in vitro and in vivo genotoxicity of Angelica acutiloba in a standard battery of assays. Lab Anim Res 33:231–236
Zeiger E (2013) Bacterial mutation assays. Methods Mol Biol 1044:3–26
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This work 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, and the National Research Foundation (NRF) of Korea funded by the Korean Government (RS-2023-00219517).
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HSS designed the research plan. HSS, JSK, MKP, NWS, GHK, SHK, JSK, SHK, JCK, and CM performed the experiments and analyzed the data. HSS, JCK, and CM wrote the manuscript.
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The protocols for the animal study were approved by the Institutional Animal Care and Use Committee of Korea Testing and Research Institute (IAC2020-2809).
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Seo, HS., Kim, JS., Park, MK. et al. Genotoxicity evaluation of collagen peptide derived from skate (Raja kenojei) skin: In vitro and in vivo studies. Mol. Cell. Toxicol. (2024). https://doi.org/10.1007/s13273-023-00423-5
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DOI: https://doi.org/10.1007/s13273-023-00423-5