Browse > Article
http://dx.doi.org/10.22537/jksct.16.2.108

The Effect of Glehnia Littoralis on Alpha-amanitin Induced Hepatotoxicity in a Murine Model  

Ryu, Chang Yeon (Department of Emergency Medicine, School of Medicine, Chosun University)
Sun, Kyung Hoon (Department of Emergency Medicine, School of Medicine, Chosun University)
Hong, Ran (Department of Pathology, School of Medicine, Chosun University)
Park, Yongjin (Department of Emergency Medicine, School of Medicine, Chosun University)
Publication Information
Journal of The Korean Society of Clinical Toxicology / v.16, no.2, 2018 , pp. 108-115 More about this Journal
Abstract
Purpose: Glehnia littoralis has been reported to have several pharmacological properties but no in vivo reports describing the protective effects of this plant on${\alpha}$-amanitin-induced hepatotoxicity have been published. ${\alpha}$-Amanitin is a peptide found in several mushroom species that accounts for the majority of severe mushroom poisonings leading to severe hepatonecrosis. In our previous in vitro study, we found that ${\alpha}$-amanitin induced oxidative stress, which may contribute to its severe hepatotoxicity. The aim of this study was to investigate whether Glehnia littoralis acetate extract (GLEA) has protective antioxidant effects on ${\alpha}$-amanitin-induced hepatotoxicity in a murine model. Methods: Swiss mice (n=40 in all groups) were divided into four groups (n=10/group). Three hours after giving ${\alpha}$-amanitin (0.6 mg/kg, i.p.) to the mice, they were administered silibinin (50 mg/kg/d, i.p.) or Glehnia littoralis ethyl acetate extract (100 mg/kg/d, oral) therapies once a day for 3 days. After 72 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurement, and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was assessed by a pathologist blinded to the treatment group and divided into 4 categories according to the grade of hepatonecrosis. Results: GLEA significantly improved the beneficial functional parameters in ${\alpha}$-amanitin-induced hepatotoxicity. In the histopathological evaluation, the toxicity that was generated with ${\alpha}$-amanitin was significantly reduced by GLEA, showing a possible hepatoprotective effect. Conclusion: In this murine model, Glehnia littoralis was effective in limiting hepatic injury after ${\alpha}$-amanitin poisoning. Increases of aminotransferases and degrees of hepatonecrosis were attenuated by this antidotal therapy.
Keywords
Alpha-amanitin; Glehnia littoralis; Antioxidant; Antidotes; Animal model;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Institute KFR. National Academy of Agricultural Science. Poisonous mushroom in the woods. In. Seoul: Korea Forest Research Institute; 2014.
2 Schenk-Jaeger KM, Rauber-Luthy C, Bodmer M, Kupferschmidt H, Kullak-Ublick GA, Ceschi A. Mushroom poisoning: a study on circumstances of exposure and patterns of toxicity. European journal of internal medicine 2012;23:e85-e91.   DOI
3 Unluoglu I, Tayfur M. Mushroom poisoning: an analysis of the data between 1996 and 2000. European Journal of Emergency Medicine 2003;10:23-6.   DOI
4 Kroncke K, Fricker G, Meier P, Gerok W, Wieland T, Kurz G. alpha-Amanitin uptake into hepatocytes. Identification of hepatic membrane transport systems used by amatoxins. Journal of biological chemistry 1986;261:12562-7.
5 Escudi? L, Francoz C, Vinel J-P, Moucari R, Cournot M, Paradis V, et al. Amanita phalloides poisoning: reassessment of prognostic factors and indications for emergency liver transplantation. Journal of Hepatology 2007;46:466-73.   DOI
6 Jan MA, Siddiqui TS, Ahmed N, Ul-Haq I, Khan Z. Mushroom poisoning in children: clinical presentation and outcome. J Ayub Med Coll Abbottabad 2008;20:99-101.
7 Zheleva A, Tolekova A, Zhelev M, Dobreva Z, Halacheva K, Popova S. In vivo antioxidant and prooxidant properties of Amanita phalloides mushroom toxins. Trakia J Sci 2005;3:34-8.
8 Zheleva A, Gadjeva V, Zhelev M. Free radical formation might contribute to the severe amatoxin hepatotoxicity. Trakia J Sci 2003;1:42-5.
9 Zheleva A, Tolekova A, Zhelev M, Uzunova V, Platikanova M, Gadzheva V. Free radical reactions might contribute to severe alpha amanitin hepatotoxicity-a hypothesis. Medical hypotheses 2007;69:361-7.   DOI
10 Ng T, Liu F, Wang H. The antioxidant effects of aqueous and organic extracts of Panax quinquefolium, Panax notoginseng, Codonopsis pilosula, Pseudostellaria heterophylla and Glehnia littoralis. Journal of ethnopharmacology 2004;93:285-8.   DOI
11 Kong C-S, Um YR, Im Lee J, Kim YA, Yea SS, Seo Y. Constituents isolated from Glehnia littoralis suppress proliferations of human cancer cells and MMP expression in HT1080 cells. Food chemistry 2010;120:385-94.   DOI
12 Um YR, Kong C-S, Im Lee J, Kim YA, Nam TJ, Seo Y. Evaluation of chemical constituents from Glehnia littoralis for antiproliferative activity against HT-29 human colon cancer cells. Process Biochemistry 2010;45:114-9.   DOI
13 Yoon T, Lee DY, Lee AY, Choi G, Choo BK, Kim HK. Antiinflammatory effects of Glehnia littoralis extract in acute and chronic cutaneous inflammation. Immunopharmacology and immunotoxicology 2010;32:663-70.   DOI
14 Busi C, Fiume L, Costantino D, Langer M, Vesconi F. Amanita toxins in gastroduodenal fluid of patients poisoned by the mushroom, Amanita phalloides. New England Journal of Medicine 1979;300:800-.
15 Nakano Y, Matsunaga H, Saita T, MORI M, KATANO M, OKABE H. 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. Biological and Pharmaceutical Bulletin 1998;21:257-61.   DOI
16 Bo Hyun K, Kyung Hoon S, Sun Pyo K, Yongjin P. In vitro Protective Effects of Glehnia Littoralis on Alpha-amanitin Induced Hepatotoxicity. J Korean Soc Clin Toxicol 2017;15:107-15.
17 Tong TC, Hernandez M, Richardson III WH, Betten DP, Favata M, Riffenburgh RH, et al. Comparative treatment of ${\alpha}$-amanitin poisoning with N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin in a murine model. Annals of emergency medicine 2007;50:282-8.   DOI
18 Gupta N, Pant S, Vijayaraghavan R, Rao PL. Comparative toxicity evaluation of cyanobacterial cyclic peptide toxin microcystin variants (LR, RR, YR) in mice. Toxicology 2003;188:285-96.   DOI
19 Fantozzi R, Ledda F, Caramelli L, Moroni F, Blandina P, Masini E, et al. Clinical findings and follow-up evaluation of an outbreak of mushroom poisoning-survey of Amanita phalloides poisoning. Klinische Wochenschrift 1986;64:38-43.   DOI
20 Yilmaz I, Ermis F, Akata I, Kaya E. A Case Study: What Doses of Amanita phalloides and Amatoxins Are Lethal to Humans? Wilderness Environ Med 2015;26:491-6.   DOI
21 Marciniak B, Lopaczynska D, Kowalczyk E, Skoskiewicz J, Witczak M, Majczyk M, et al. Evaluation of micronuclei in mice bone marrow and antioxidant systems in erythrocytes exposed to alpha-amanitin. Toxicon 2013;63:147-53.   DOI
22 Huang G-J, Deng J-S, Liao J-C, Hou W-C, Wang S-Y, Sung P-J, et al. Inducible nitric oxide synthase and cyclooxygenase-2 participate in anti-inflammatory activity of imperatorin from Glehnia littoralis. Journal of agricultural and food chemistry 2012;60:1673-81.   DOI
23 Poucheret P, Fons F, Dore JC, Michelot D, Rapior S. Amatoxin poisoning treatment decision-making: pharmaco-therapeutic clinical strategy assessment using multidimensional multivariate statistic analysis. Toxicon 2010;55:1338-45.   DOI
24 Molander D, Wroblewski F, La Due J. Transaminase compared withcholinesterase and alkaline phosphatase an index of hepatocellular integrity. In: CLINICAL RESEARCH PROCEEDINGS; 1955.
25 Enjalbert F, Rapior S, Nouguier-Soule J, Guillon S, Amouroux N, Cabot C. Treatment of amatoxin poisoning: 20-year retrospective analysis. J Toxicol Clin Toxicol 2002;40:715-57.   DOI
26 Magdalan J, Ostrowska A, Piotrowska A, Gomulkiewicz A, Podhorska-Okolow M, Patrzalek D, et al. Benzylpenicillin, acetylcysteine and silibinin as antidotes in human hepatocytes intoxicated with alpha-amanitin. Exp Toxicol Pathol 2010;62:367-73.   DOI
27 Zhang L, Ravipati AS, Koyyalamudi SR, Jeong SC, Reddy N, Smith PT, et al. Antioxidant and anti-inflammatory activities of selected medicinal plants containing phenolic and flavonoid compounds. Journal of agricultural and food chemistry 2011;59:12361-7.   DOI
28 Yoon T, Cheon MS, Lee AY, Do YL, Moon BC, Chun JM, et al. Anti-inflammatory activity of methylene chloride fraction from Glehnia littoralis extract via suppression of $NF-{\kappa}B$ and mitogen-activated protein kinase activity. Journal of pharmacological sciences 2010;112:46-55.   DOI
29 Magdalan J, Piotrowska A, GomuŁkiewicz A, Sozanski T, Podhorska-OkoŁow M, Szelag A, et al. Benzylpenicyllin and acetylcysteine protection from ${\alpha}$-amanitin-induced apoptosis in human hepatocyte cultures. Experimental and toxicologic pathology 2011;63:311-5.   DOI