글루타치온을 이용한 피부접촉물질에 초기 독성 탐색 기술
Initial Toxicity Screening Techniques of Skin Contact Materials Using Glutathione
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목적: 화학물질의 대사계인 S9 fraction를 이용하는 유전독성시험 in vitro 시스템에 단백질-유사 기능으로 기대되는 glutathione (GSH)를 추가하여 화학물질의 피부의 자극성 및 감작성을 탐색할 수 있는 동물대체시험법으로 glutathione-containing screen system (GCS system)을 개발하는 것이 목적이다. 방법: 자극성 및 감작성의 물질은 유해활성산소 및 유기 라디칼을 생성하거나 단백질과 결합하여 GSH 감소 및 GSH 산화형인 glutathione disulfide (GSSG)의 증가를 유도한다. 이러한 점을 고려하여 자극성 및감작성을 탐색하기 위해 total GSH와 GSSG/GSH 비 등의 GSH 변화를 측정하였다. 결과: 피부자극성 양성물질인 heptanal에 의해 total GSH가 감소되어 자연분해를 통해 활성화되며 피부감작성 양성물질인 eugenol은 total GSH 감소와 더불어 GSSG/GSH ratio 증가가 유도되어 효소에 의한 생화학적 전환을 통해 활성화되는 indirect-acting toxicant로 추정되었다. 결론: 이러한 결과를 고려할 때 피부자극성물질은 S9 fraction이 없는 direct system, 피부감작성물질은 S9 fraction을 포함하고 있는 indirect system에서 GSH에 대한 영향이 클 것으로 추정되었다. 그러나 GCS system의 direct system와 indirect system에서 더 많은 양성물질을 이용한 연구를 통해 시스템에서의 자극성 및 감작성의 잠재적 경향성을 파악하여 개발의 필요성이 있다.
Abstract
Purpose: We developed a glutathione-containing screening (GCS) system capable of confirming toxicity at the substance screening stage aimed at reducing the time and cost of the cosmetic raw material development stage. Methods: Based on genotoxicity testing, a GCS system, comprising a direct and indirect system, was developed to reduce the time and cost to identify toxicity during the screening of candidate cosmetic substances. Toxicity potential was confirmed by identifying changes in the content of total glutathione (GSH), which conjugates only toxic substances, and those in the glutathione disulfide (GSSG)/GSH ratio. Results: Heptanal, a positive control substance in skin irritation tests, showed a decrease in total GSH and was identified as a direct-acting toxicant. Eugenol, a positive control substance in skin sensitization tests, showed a decrease in total GSH and an altered GSSG/GSH ratio and was identified as an indirect-acting toxicant. Conclusion: The GCS system could identify toxicity characteristics of skin irritation and sensitization. However, more positive chemicals are required to induce skin irritation or sensitization to challenge a chemical's toxic classification such as irritation or sensitization according to the GCS system, direct and indirect systems.
참고문헌 (44)
- Agner T, "Sodium lauryl sulphate for irritant patch testing : a dose-response study using bioengineering methods for determination of skin irritation", Journal of Investigative Dermatology, 95, pp.543~547 (1990)
- Ahmad N, "Cytochrome p450: a target for drug development for skin diseases", Journal of Investigative Dermatology, 123, pp.417~425 (2004)
- Anadón A, "The role of in vitro methods as alternatives to animals in toxicity testing", Expert Opinion on Drug Metabolism & Toxicology, 10, pp.67~79 (2014)
- Bandyopadhyay U, "Reactive oxygen species: oxidative damage and pathogenesis", Current Science, 77, pp.658~666 (1999)
- Barel AO, "Handbook of cosmetic science and technology", pp.353~365 (2014), CRC press
- Bergström MA, "A skinlike cytochrome P450 cocktail activates prohaptens to contact allergenic metabolites", Journal of Investigative Dermatology, 127, pp.1145~1153 (2007)
- Betharia S, "Encyclopedia of toxicology", pp.165~175 (2014), Elsevier Academic Press
- Clayton GD, "Patty's industrial hygiene and toxicology", pp.2635~ (1982), Wiley Interscience
- Dupuis G, "Allergic contact dermatitis to alpha-methylene-gamma-butyrolactones. preparation of alantolactone–protein conjugates and induction of contact", Molecular Immunology, 17, pp.1045~1051 (1980)
- Golla S, "Quantitative structure-property relationships modeling of skin irritation", Toxicology in Vitro, 23, pp.176~184 (2009)
- Götz C, "Xenobiotic metabolism capacities of human skin in comparison with a 3D epidermis model and keratinocyte-based cell culture as in vitro alternatives for chemical testing: activating enzymes (Phase I)", Experimental Dermatology, 21, pp.358~363 (2012)
- 홍양희, "기능성 소재 개발을 위한 돼지태반추출물의 경구 및 피부 동물모델 안정성 평가", 아시안뷰티화장품학술지, 12(5), pp.733~743 (2014), 한국피부과학연구원
- Jones DP, "Redox potential of GSH", GSSG couple: assay and biological significance, 2002, pp.348, 93~112
- Jugert FK, "Multiple cytochrome P450 isozymes in murine skin : induction of P450 1A, 2B, 2E, and 3A by dexamethasone", Journal of Investigative Dermatology, 102, pp.970~975 (1994)
- Kaplowitz N, "Idiosyncratic drug hepatotoxicity", Nature Reviews Drug Discovery, 4, pp.489~499 (2005)
- Khan WA, "Monoclonal antibodies directed characterization of epidermal and hepatic cytochrome P-450 isozymes induced by skin application of therapeutic crude coal tar", Journal of Investigative Dermatology, 93, pp.40~45 (1989)
- 김배환, "인공피부를 이용한 피부자극 대체시험법 소개", 아시안뷰티화장품학술지, 9(2), pp.139~147 (2011), 한국피부과학연구원
- 이아영, "인체피부모델을 이용한 미백 효능물질 PF3758309의 in vitro 피부 자극성 평가", 아시안뷰티화장품학술지, 16(3), pp.417~425 (2018), 한국피부과학연구원[DOI]
- 이진구, "선진 외국의 동물대체시험법 개발현황과 전망", 한국동물실험대체법학회지, 10(1), pp.1~16 (2016), 한국동물실험대체법학회[DOI]
- 이경은, "각질형성세포에서 LPS로 유도된 염증반응에 대한 마가목, 쐐기풀, 죽여 및 오배자 혼합추출물의 항염 효과", 대한화장품학회지, 40(1), pp.45~54 (2014), 사단법인 대한화장품학회[DOI]
- LoPachin RM, "Protein adduct formation as a molecular mechanism in neurotoxicity", Toxicological Science, 86, pp.214~225 (2005)
- Lu SC, "Regulation of glutathione synthesis", Molecular Aspects of Medicine, 30, pp.42~59 (2009)
- Madden JC, "In silico prediction of skin metabolism and its implication in toxicity assessment", Computational Toxicology, 3, pp.44~57 (2017)
- Mercer AE, "Functional and toxicological consequences of metabolic bioactivation of methapyrilene via thiophene S-oxidation: induction of cell defence, apoptosis and hepatic necrosis", Toxicology and Applied Pharmacology, 239, pp.297~305 (2009)
- Merk HF, "Dermatotoxicology", pp.61~73 (1996), Taylor and Francis
- Nizioł-Łukaszewska Z, "Hydrophilic dogwood extracts as materials for reducing the skin irritation potential of body wash cosmetics", Molecules, 22, pp.E320~ (2017)
- OECD, "Test No. 471: bacterial reverse mutation test, OECD guidelines for the testing of chemicals, section 4", OECD Publishing, ~ (1997)
- OECD, "Test No. 439: in vitro skin irritation: reconstructed human epidermis test method, OECD guidelines for the testing of chemicals, section 4", OECD Publishing, ~ (2013)
- OECD, "Test No. 473: in vitro mammalian chromosomal aberration test, OECD guidelines for the testing of Chemicals, section 4", OECD Publishing, ~ (2016)
- OECD, "Test No.429: skin sensitization: local lymph node assay, OECD guidelines for the testing of chemicals, section 4", OECD Publishing, ~ (2010)
- OECD, "Test No. 442A: skin sensitization: local lymph node assay: DA, OECD guidelines for the testing of chemicals, section 4", OECD Publishing, ~ (2010)
- OECD, "Test No. 442B: skin sensitization: local lymph node assay: BrdU-ELISA or –FCM, OECD guidelines for the testing of Chemicals, section 4", OECD Publishing, ~ (2018)
- 박영철, "The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a “Central Dogma” for Toxic Mechanisms?", 한국독성학회지, 30(3), pp.179~184 (2014), 한국독성학회[DOI]
- Park YC, "The molecular & biochemical principles for toxicology", pp.23~ (2010), Korean studies information
- Patlewicz G, "Skin-sensitization structure-activity relationships for aldehydes", Contact Dermatitis, 44, pp.331~336 (2001)
- Reisinger K, "Systematic evaluation of non-animal test methods for skin sensitisation safety assessment", Toxicology in Vitro, 29, pp.259~270 (2015)
- Rhein LD, "Surfactants in personal care products and decorative cosmetics", pp.345~ (2006), CRC Press
- Son JS, "Review of alternative methods for the safety assessment of cosmetic ingredients : in terms of skin irritation, sensitization and phototoxicity", Journal of Cancer Prevention, 17, pp.270~279 (2012)
- Thompson D, "Formation of glutathione conjugates during oxidation of eugenol by microsomal fractions of rat liver and lung", Biochemical Pharmacology, 39, pp.1587~1595 (1990)
- Welss T, "In vitro skin irritation:facts and future. state of the art review of mechanisms and models", Toxicology in Vitro, 18, pp.231~243 (2004)
- Weston JK, "Activation of inflammasomes by agents causing idiosyncratic skin reactions: a possible biomarker", Chemical Research in Toxicology, 27, pp.949~951 (2014)
- Winterbourn CC, "Thiol chemistry and specificity in redox signaling", Free Radical Biology and Medicine, 45, pp.549~561 (2008)
- Yang SM, "Investigation method for toxicity profile of cosmetics ingredients and trends in safety evaluation", Regulatory Research on Food, Drug & Cosmetic, 10, pp.131~139 (2015)
- Yin H, "Free radical lipid peroxidation : mechanisms and analysis", Chemical reviews, 111, pp.5944~5972 (2011)