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알파 아마니틴에 의한 간독성에 대한 갯방풍의 보호 효과

In vitro Protective Effects of Glehnia Littoralis on Alpha-amanitin Induced Hepatotoxicity

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Purpose: Glehnia littoralis has been used to treat ischemic stroke, phlegm, cough, systemic paralysis, antipyretics and neuralgia. The pharmacological mechanisms of Glehnia littoralis include calcium channel block, coumarin derivatives, anticoagulation, anti-convulsive effect, as well as anti-oxidant and anti-inflammatory effects. Alpha-amanitin (α-amanitin) is a major toxin from extremely poisonous Amanita fungi. Oxidative stress, which may contribute to severe hepatotoxicity was induced by α-amanitin. The aim of this study was to investigate whether Glehnia littoralis ethyl acetate extract (GLEA) has the protective antioxidant effects on α-amanitin -induced hepatotoxicity. Methods: Human hepatoma cell line HepG2 cells were pretreated in the presence or absence of GLEA (50, 100 and 200μg/ml) for 4 hours, then exposed to 60μmol/L ofα-amanitin for an additional 4 hours. Cell viability was evaluated using the MTT method. AST, ALT, and LDH production in a culture medium and intracellular MDA, GSH, and SOD levels were determined. Results: GLEA (50, 100 and 200μg/ml) significantly increased the relative cell viability by 7.11, 9.87, and 14.39%, respectively, and reduced the level of ALT by 10.39%, 34.27%, and 52.14%, AST by 9.89%, 15.16%, and 32.84%, as well as LDH by 15.86%, 22.98%, and 24.32% in culture medium, respectively. GLEA could also remarkably decrease the level of MDA and increase the content of GSH and SOD in the HepG2 cells. Conclusion: In the in vitro model, Glehnia littoralis was effective in limiting hepatic injury afterα-amanitin poisoning. Its antioxidant effect is attenuated by antidotal therapy.

Abstract

Purpose: Glehnia littoralis has been used to treat ischemic stroke, phlegm, cough, systemic paralysis, antipyretics and neuralgia. The pharmacological mechanisms of Glehnia littoralis include calcium channel block, coumarin derivatives, anticoagulation, anti-convulsive effect, as well as anti-oxidant and anti-inflammatory effects. Alpha-amanitin (α-amanitin) is a major toxin from extremely poisonous Amanita fungi. Oxidative stress, which may contribute to severe hepatotoxicity was induced by α-amanitin. The aim of this study was to investigate whether Glehnia littoralis ethyl acetate extract (GLEA) has the protective antioxidant effects on α-amanitin -induced hepatotoxicity. Methods: Human hepatoma cell line HepG2 cells were pretreated in the presence or absence of GLEA (50, 100 and 200μg/ml) for 4 hours, then exposed to 60μmol/L ofα-amanitin for an additional 4 hours. Cell viability was evaluated using the MTT method. AST, ALT, and LDH production in a culture medium and intracellular MDA, GSH, and SOD levels were determined. Results: GLEA (50, 100 and 200μg/ml) significantly increased the relative cell viability by 7.11, 9.87, and 14.39%, respectively, and reduced the level of ALT by 10.39%, 34.27%, and 52.14%, AST by 9.89%, 15.16%, and 32.84%, as well as LDH by 15.86%, 22.98%, and 24.32% in culture medium, respectively. GLEA could also remarkably decrease the level of MDA and increase the content of GSH and SOD in the HepG2 cells. Conclusion: In the in vitro model, Glehnia littoralis was effective in limiting hepatic injury afterα-amanitin poisoning. Its antioxidant effect is attenuated by antidotal therapy.

참고문헌 (27)

  1. 서영완, "염생식물로부터 Peroxynitrite와 DPPH 라디칼 소거 활성 검색", KSBB Journal, 19(1), pp.57~61 (2004), 한국생물공학회
  2. Ng T, "The antioxidant effects of aqueous and organic extracts of Panax quinquefolium, Panax notoginseng, Codonopsis pilosula, Pseudostellaria heterophylla and Glehnia littoralis", J Ethnopharmacol, 93, pp.285~288 (2004)
  3. Nakano Y, "Antiproliferative Constituents in Umbelliferae Plants II.: Screening for Polyacetylenes in Some Umbelliferae Plants, and Isolation of Panaxynol and Falcarindiol from the Root of Heracleum moellendorffii", Biol Pharma Bull, 21, pp.257~261 (1998)
  4. Han M, "Effects of 24 Chinese medicinal herbs on nucleic acid, protein and cell cycle of human lung adenocarcinoma cell", Zhongguo Zhong Xi Yi Jie He Za Zhi, 15, pp.147~149 (1995)
  5. Li J, "Biphenyl ferulate from Glehnia littoralis", Zhongguo Zhong Xi Yi Jie He Za Zhi, 28, pp.553~555 (2005)
  6. Wang S, "Experimental study on effects of 18kinds of Chinese herbal medicine for synthesis of thromboxane A2 and PGI2", Zhongguo Zhong Xi Yi Jie He Za Zhi, 13, pp.167~170 (1993)
  7. Fang X, "The immunosuppressive activities of polysaccharides from Glehnia littoralis (bei sha shen)", Yao xue xue bao, 21, pp.931~934 (1986)
  8. McCutcheon A, "Antifungal screening of medicinal plants of British Columbian native peoples", J Ethnopharmacol, 44, pp.157~169 (1994)
  9. Deutsch M, "Amanita phalloides poisoning: reassessment of prognostic factors and indications for emergency liver transplantation", J hepatol, 47, pp.728~729 (2007)
  10. DÜNDAR ZD, "The role of oxidative stress inα-amanitin-induced hepatotoxicity in an experimental mouse model", Turk J Med Sci, 47 (2017)
  11. Zheleva A, "Free radical reactions might contribute to severe alpha amanitin hepatotoxicity-a hypothesis", Med hypotheses, 69, pp.361~367 (2007)
  12. Nikolova G, "severe mushroom toxin alpha amanitin causes generation of reactive oxygen species in liver tissues of mice-a comparative study by two different instrumental methods", Trakia Journal of Sciences, 8, pp.149~154 (2010)
  13. Wu X, "Hepatoprotective Effects of Aqueous Extract from Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Higher Basidiomycetes) on α-Amanitin- Induced Liver Injury in Mice", Int J Med Muschrooms, 15, pp.383~391 (2013)
  14. Letschert K, "Molecular characterization and inhibition of amanitin uptake into human hepatocytes", Toxicol Sci, 91, pp.140~149 (2006)
  15. Marciniak B, "Evaluation of micronuclei in mice bone marrow and antioxidant systems in erythrocytes exposed to alpha-amanitin", Toxicon, 63, pp.147~153 (2013)
  16. Poucheret P, "Amatoxin poisoning treatment decision-making: pharmaco-therapeutic clinical strategy assessment using multidimensional multivariate statistic analysis", Toxicon, 55, pp.1338~1345 (2010)
  17. Enjalbert F, "Treatment of amatoxin poisoning:20-year retrospective analysis", J Toxicol Clin Toxicol, 40, pp.715~757 (2002)
  18. Yilmaz I, "A Case Study: What Doses of Amanita phalloides and Amatoxins Are Lethal to Humans?", Wilderness Environ Med, 26, pp.491~496 (2015)
  19. Magdalan J, "Failure of benzylpenicillin, Nacetylcysteine and silibinin to reduce alpha-amanitin hepatotoxicity", In Vivo, 23, pp.393~399 (2009)
  20. Magdalan J, "Benzylpenicillin, acetylcysteine and silibinin as antidotes in human hepatocytes intoxicated with alpha-amanitin", Exp Toxicol Pathol, 62, pp.367~373 (2010)
  21. Tong TC, "Comparative treatment of alpha-amanitin poisoning with N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin in a murine model", Ann Emerg Med, 50, pp.282~288 (2007)
  22. Yuan Z, "Constituents ofthe underground parts of Glehnia littoralis", Chem Pharm Bull (Tokyo), 50, pp.73~77 (2002)
  23. Krithika R, "Isolation, characterization and antioxidative effect of phyllanthin against CCl4-induced toxicity in HepG2 cell line", Chem Biol Interact, 181, pp.351~358 (2009)
  24. Cherubini A, "Potential markers of oxidative stress in stroke", Free Radic Biol Med, 39, pp.841~852 (2005)
  25. Kim KA, "Mechanism of refractory ceramic fiber- and rock woolinduced cytotoxicity in alveolar macrophages", Int Arch Occup Environ Health, 74, pp.9~15 (2001)
  26. Khanal T, "Saponins isolated from the root of Platycodon grandiflorum protect against acute ethanol-induced hepatotoxicity in mice", Food Chem Toxicol, 47, pp.530~535 (2009)
  27. de Freitas RB, "Hepatotoxicity evaluation of aqueous extract from Scutia buxifolia", Molecules, 18, pp.7570~7583 (2013)

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