Hostname: page-component-745bb68f8f-b95js Total loading time: 0 Render date: 2025-01-22T04:10:55.491Z Has data issue: false hasContentIssue false
  • English
  • Français

Hepatotoxicity of botanicals†

Published online by Cambridge University Press:  02 January 2007

Felix Stickel ,
Gerlinde Egerer  and
Helmut Karl Seitz
Felix Stickel*
Affiliation:
Department of Medicine and Gastroenterology, Krankenhaus der Barmherzigen Brüder, Technical University of Munich, D-80639 Munich, Germany;
Gerlinde Egerer
Affiliation:
Medizinishe Poliklinik, University of Heidelberg, Heidelberg, Germany;
Helmut Karl Seitz
Affiliation:
Laboratory of Alcohol Research and Nutrition, Salem Medical Center, Heidelberg, Germany
*
*Corresponding author.
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Objective

Hepatic impairment resulting from the use of conventional drugs is widely acknowledged, but there is less awareness of the potential hepatotoxicity of herbal preparations and other botanicals, many of which are believed to be harmless and are commonly used for self-medication without supervision. The aim of this paper is to examine the evidence for hepatotoxicity of botanicals and draw conclusions regarding their pathology, safety and applications.

Design

Current literature on the hepatotoxicity of herbal drugs and other botanicals is reviewed. The aetiology, clinical picture and treatment of mushroom (Amanita) poisoning are described.

Results

Hepatotoxic effects have been reported for some Chinese herbal medicines (such as Jin Bu Huan, Ma-Huang and Sho-saiko-to), pyrrolizidine alkaloid-containing plants, germander (Teucrium chamaedrys), chaparral (Larrea tridentata), Atractylis gummifera, Callilepsis laureola, and others. The frequency with which botanicals cause hepatic damage is unclear. There is a lack of controlled treatment trials and the few studies published to date do not clarify the incidence of adverse effects. Many plant products do not seem to lead to toxic effects in everyone taking them, and they commonly lack a strict dose-dependency. For some products, such as Sho-saiko-to, the picture is confused further by demonstrations of hepatoprotective properties for some components. Mushroom poisoning is mostly due to the accidental consumption of Amanita species. Treatment with silymarin, thioctic acid, penicillin and liver transplantation have been shown to be effective but require early diagnosis.

Conclusions

Severe liver injury, including acute and chronic abnormalities and even cirrhotic transformation and liver failure, has been described after the ingestion of a wide range of herbal products and other botanical ingredients, such as mushrooms. It is concluded that in certain situations herbal products may be just as harmful as conventional drugs.

Keywords

Herbal medicineChinese medicineGermanderPyrrolizidine alkaloidsChaparralHerbal hepatotoxicityAmanitaMushroom poisoningToxic liver injury
Type
Research Article
Information
Public Health Nutrition , Volume 3 , Issue 2 , June 2000 , pp. 113 - 124
Copyright
Copyright © CABI Publishing 2000

Footnotes

†

This paper is the third in a series on medicinal herbs.

References

1Sherlock, S, Dooley, J. Drugs and the liver. In: Sherlock, S, Dooley, J, eds. Diseases of the Liver and Biliary System, 10th edn.Oxford: Blackwell Science, 1997: 337–69.Google Scholar
2Nebert, DW, Nelson, DR, Coon, MJ, et al. . The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol 1991; 10(1): 1–14.CrossRefGoogle ScholarPubMed
3Taylor-Reilly, P.Young doctor's view on alternative medicine. BMJ 1983; 287: 337–9.CrossRefGoogle Scholar
4Moore, J, Phipps, K, Marcer, D, Lewith, G.Why do people seek treatment by alternative medicine. BMJ 1985; 290: 28–9.CrossRefGoogle ScholarPubMed
5Eisenberg, DM, Kessler, RC, Foster, C, Norlock, FE, Collins, DR and Delbanco, TL. Unconventional medicine in the United States. Prevalence, costs and patterns of use. N. Engl. J. Med. 1993; 328: 246–52.CrossRefGoogle ScholarPubMed
6Ridker, PM. Toxic effects of herbal tea. Arch. Environ. Health 1987; 42: 133–6.CrossRefGoogle Scholar
7Schiano, T. Liver injury from herbs and other botanicals. In: Gitlin, N, ed. Clinics in Liver Disease. Chicago: WB Saunders, 1998: 607–30.Google Scholar
8Carlsson, C.Herbs and hepatitis. Lancet 1990; 336: 1068.CrossRefGoogle ScholarPubMed
9Chan, TYK, Chan, JCN, Tomlinson, B, Critchley, AJH. Chinese herbal medicines revisited: a Hong Kong perspective. Lancet 1993; 342: 1532–4.CrossRefGoogle ScholarPubMed
10Sheehan, MP, Rustin, MHA, Atherton, DJ, et al. Efficacy of traditional Chinese herbal therapy in adult atopic dermatitis. Lancet 1992; 340: 13–17.CrossRefGoogle ScholarPubMed
11Sheehan, MP, Atherton, DJ. A controlled trial of traditional Chinese medicinal plants in widespread non-exudative atopic eczema. Br. J. Dermatol. 1992; 126: 179–84.CrossRefGoogle ScholarPubMed
12Davies, EG, Pollock, I, Steel, HM. Chinese herbs for eczema. Lancet 1990; 336: 38.Google Scholar
13Graham-Brown, R.Toxicity of Chinese herbal remedies. Lancet 1992; 346: 674.Google Scholar
14Perharic-Walton, L, Murray, V.Toxicity of traditional Chinese herbal remedies. Lancet 1992; 346: 674.Google Scholar
15Kane, JA, Kane, SP, Jain, S.Hepatitis induced by traditional Chinese herbs; possible toxic components. Gut 1995; 36: 146–7.CrossRefGoogle ScholarPubMed
16Yoshida, EM, McLean, CA, Cheng, ES, et al. Chinese herbal medicine, fulminant hepatitis and liver transplantation. Am. J. Gastroenterol. 1996; 12: 2647–8.Google Scholar
17Woolf, GM, Petrovic, LM, Roiter, SE, Wainwright, S, Villamil, FG, Katkow, WN. Acute hepatitis associated with the Chinese herbal product Jin Bu Huan. Ann. Intern. Med. 1994; 10: 729–35.CrossRefGoogle Scholar
18Piciotto, A, Campo, N, Brizzolara, R, et al. Chronic hepatitis induced by Jin Bu Huan. J. Hepatol. 1998; 28: 165–7.CrossRefGoogle Scholar
19Nadir, A, Agrawal, S, King, PD, Marshall, JB. Acute hepatitis associated with the use of a Chinese herbal product, Ma-Huang. Am. J. Gastroenterol. 1996; 91: 1436–8.Google ScholarPubMed
20Mowrey, DB. The major scientific breakthrough of the 90's. Reducing body fat through thermogenics. Health Store News 1994; 11: 1–4.Google Scholar
21Benichou, C.Criteria of drug-induced liver disorders. Report of an international consensus meeting. J. Hepatol. 1990; 11: 272–6.Google ScholarPubMed
22Huxtable, RJ. The myth of beneficient nature: the risks of herbal preparations. Ann. Intern. Med. 1992; 117: 165–6.CrossRefGoogle Scholar
23Wu, TN, Yang, KC, Lai, JS, Ko, KN, Chang, PY, Lion, SH. Lead poisoning caused by contaminated cordyceps, a Chinese herbal preparation. Sci. Total Environ. 1996; 182: 193–5.CrossRefGoogle Scholar
24Galloway, JH, Marsh, ID, Bittiner, ID, Messenger, AG, Gawkrodger, DJ, Glet, R.Chinese herbs for eczema, the active compound?. Lancet 1991; 337: 566.CrossRefGoogle ScholarPubMed
25Itoh, S, Marutani, K, Nishijima, T.Liver injuries induced by herbal medicine, sho-saiko-to (xiao-chai-hu-tang). Dig. Dis. Sci. 1995; 8: 1845–8.CrossRefGoogle Scholar
26Okah, H, Yamamoto, S, Kuroki, T, Harihara, S, Marumo, T, Kim, SR. Prospective study of chemoprevention of hepatocellular carcinoma with sho-saiko-to (TJ-9). Cancer 1995; 76: 743–9.3.0.CO;2-V>CrossRefGoogle Scholar
27Yano, H, Mizoguchi, A, Fukuda, K, Haramaki, M, Ogasawara, S, Momosaki, S.The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase. Cancer Res. 1994; 54: 448–54.Google ScholarPubMed
28Sakaida, I, Matsumura, Y, Akiyama, S, Hayashi, K, Ishige, A, Okita, K.Herbal medicine sho-saiko-to (TJ-9) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet. J. Hepatol. 1998; 28: 298–306.CrossRefGoogle ScholarPubMed
29Yamashiki, M, Nishimura, A, Suzuki, H, Sakaguchi, S, Kosaka, Y.Effects of the Japanese herbal medicine ‘sho-saiko-to’ (TJ-9) on in vitro interleukin-10 production by peripheral blood mononuclear cells of patients with chronic hepatitis C. Hepatology 1997; 25: 1390–7.CrossRefGoogle ScholarPubMed
30Batey, RG, Bensoussan, A, Fan Yang, Yi, Bollipo, S, Hossain, M.Preliminary report of a randomized, double-blind placebo-controlled trial of a Chinese herbal medicine preparation CH-100 in the treatment of chronic hepatitis C. J. Gastroenterol. Hepatol. 1998; 13: 244–7.CrossRefGoogle ScholarPubMed
31Wilmot, FC, Robertson, GW. Senecio disease or cirrhosis of the liver due to senecio poisoning. Lancet 1920; ii: 828–9.Google Scholar
32Bras, G, Jeliffe, DB, Stuart, KL. Veno-occlusive disease of the liver with non-portal type of cirrhosis occurring in Jamaica. Arch. Pathol. 1954; 57: 285.Google Scholar
33Tandon, BN, Tandon, RK, Tandon, HD, Narndranathan, M, Joshi, YK. An epidemic of veno-occlusive disease of liver in central India. Lancet 1976; ii: 271–2.CrossRefGoogle Scholar
34Datta, DV, Khuroo, MS, Mattocks, AR, Aikat, BK, Chhuttani, PN. Herbal medicine and veno-occlusive disease in India. Postgrad. Med. J. 1978; 54: 511–15.CrossRefGoogle Scholar
35Katzka, DA, Saul, SH, Jorkasky, D, Sigal, H, Reynolds, JC, Soloway, RD. Azathioprine and hepatic veno-occlusive disease in renal transplant patients. Gastroenterology 1986; 90: 446–54.CrossRefGoogle Scholar
36Stillman, AE, Huxtable, RJ, Consroe, P, Kohnen, P, Smith, S.Hepatic veno-occlusive disease due to pyrrolizidine (Senecio) poisoning in Arizona. Gastroenterology 1977; 73: 349–52.CrossRefGoogle ScholarPubMed
37Fox, DW, Hart, MC, Bergeson, PS, Jarrett, PB, Stillman, AE, Huxtable, RJ. Pyrrolizidine (Senecio) intoxication mimicking Reye's syndrome. J. Pediatr. 1978; 93: 980–2.CrossRefGoogle Scholar
38Ghanem, J, Hershko, C.Veno-occlusive disease and primary hepatic vein thrombosis in Israeli Arabs. Israel J. Med. Sci. 1981; 17: 339–47.Google ScholarPubMed
39Kumana, CR, Ng, M, Lin, HJ, Ko, W, Wu, PC, Todd, D.Hepatic veno-occlusive disease due to toxic alkaloids in herbal tea. Lancet 1983; ii: 1360–1.CrossRefGoogle Scholar
40Weston, CFM, Cooper, BT, Davies, JD, Levine, DF. Veno-occlusive disease of the liver secondary to ingestion of comfrey. BMJ 1987; 295: 183.CrossRefGoogle ScholarPubMed
41Roulet, M, Laurini, R, Rivier, L, Calame, A.Hepatic veno-occlusive disease in a newborn infant of a woman drinking herbal tea. J. Pediatr. 1988; 112: 433–6.CrossRefGoogle Scholar
42Valla, D, Benhamou, JP. Drug-induced vascular and sinusoidal lesions of the liver. Clin. Gastroenterol. 1988; 2: 481–500.Google ScholarPubMed
43Zimmermann, HJ, Lewis, JH. Chemical and toxin-induced liver disease. Gastroenterol. Clin. North Am. 1995; 24: 739.CrossRefGoogle Scholar
44Larrey, D.Hepatotoxicity of herbal remedies. J. Hepatol. 1997; 26: 47–54.CrossRefGoogle ScholarPubMed
45Ridker, PM, Ohkuma, S, McDermott, WV, Trey, C, Huxtable, RJ. Hepatic venocclusive disease associated with the consumption of pyrrolizidine-containing dietary supplements. Gastroenterology 1985; 88: 1050–4.CrossRefGoogle ScholarPubMed
46Bach, N, Thung, SN, Schaffner, F.Comfrey herb-tea-induced hepatic veno-occlusive disease. Am. J. Med. 1989; 87: 97–9.CrossRefGoogle ScholarPubMed
47Smith, LW, Culvenor, CCJ. Plant sources of hepatotoxic pyrrolizidine alkaloids. J. Nat. Prod. 1981; 44: 129–52.CrossRefGoogle ScholarPubMed
48Huxtable, RJ. The harmful potential of herbal and other plant products. Drug Safety 1990; 5 (Suppl. 1), 126–36.CrossRefGoogle ScholarPubMed
49Harris, PN, Chen, KK. Development of hepatic tumors in rats following ingestion of Senecio longilobus. Cancer Res. 1980; 30: 2881–6.Google Scholar
50Petry, TW, Bowden, GT, Huxtable, RJ, Sipes, IG. Characterization of hepatic DNA damage induced in rats by the pyrrolizidine alkaloid monocrotaline. Cancer Res. 1984; 44: 1505–9.Google ScholarPubMed
51Mattocks, AR. Chemistry and Toxicology of Pyrrolizidine Alkaloids. London: Academic Press, 1986.Google Scholar
52Tyler, VE. Plant drugs in the twenty-first century. HerbalGram 1987; 11: 6–11.Google Scholar
53Diaz, D, Ferroudji, S, Heran, B.Hépatite aigue à la Germandrée petit-chene. Gastroenterol. Clin. Biol. 1993; 16: 1006–7.Google Scholar
54Larrey, D, Vial, T, Pauwels, A, et al. Hepatitis after germander (Teucrium chamaedrys) administration: another instance of herbal medicine hepatotoxicity. Ann. Intern. Med. 1992; 117: 129–32.CrossRefGoogle ScholarPubMed
55Mostefa-Kara, N, Pauwels, A, Pines, E, Biour, C, Levy, VG. Fatal hepatitis after herbal tea. Lancet 1992; 340: 674.CrossRefGoogle ScholarPubMed
56Larrey, D, Pageaux, GP. Hepatotoxicity of herbal remedies and mushrooms. Semin. Liver Dis. 1995; 15(3), 183–8.CrossRefGoogle ScholarPubMed
57Ben Yahia, M, Mavier, P, Matreau, JM. Hépatite chronique active et cirrhose induites par la germandrée petit-chene: a propos de trois cas. Gastroenterol. Clin. Biol. 1993; 17: 959–62.Google Scholar
58Dao, T, Peytier, A, Galateau, F, Valla, A.Hépatite chronique cirrhogene a la germandrée petit-chene. Gastroenterol. Clin. Biol. 1993; 17: 609–10.Google Scholar
59Savona, G, Garcia-Alvarez, MC, Rodriguez, B.Dihydroteugin, a neo-clerodane diterpenoid from Teucrium chamaedris. Phytochemistry 1982; 21: 721–3.CrossRefGoogle Scholar
60Rodriguez, MC, Barluenga, J, Pascual, C, Rodriguez, B, Savona, G, Piozzi, F.Neo-clerodane diterpenoids from Teucrium chamaedris: the identity of teucrin B with dihydroteugin. Phytochemistry 1984; 23: 2960–1.CrossRefGoogle Scholar
61Piozzi, F, Rodriguez, B, Savona, G.Advances in the chemistry of the furanoditerpenoids from Teucrium species. Heterocycles 1987; 25: 807–41.Google Scholar
62Itoh, N, Kimura, T, Nakanishi, H, et al. Metallothionine-independent hepatoprotection by zinc and sakuraso-saponin. Toxicol. Lett. 1997; 93(2/3), 135–40.CrossRefGoogle ScholarPubMed
63Maronpot, RR, Giles, HD, Dykes, DJ, Irwin, RD. Furan-induced hepatic cholangiocarcinomas in Fisher 344 rats. Toxicol. Pathol. 1991; 19: 561–70.CrossRefGoogle Scholar
64Elmore, LW, Sirica, AE. ‘Intestinal-type’ of adenocarcinoma preferentially induced in right/caudate liver lobes of rats treated with furan. Cancer Res. 1993; 53: 254–9.Google ScholarPubMed
65Mitchell, JR, Potter, WZ, Hinson, JA, Jollow, DJ. Hepatic necrosis caused by furosemide. Nature 1974; 251: 508–11.CrossRefGoogle ScholarPubMed
66Ramsdell, HS, Parkinson, A, Eddy, AC, Eaton, DL. Bioactivation of aflatoxin B1 by human liver microsomes. Role of cytochrome P450 IIIA enzymes. Toxicol. Appl. Pharmacol. 1991; 108: 436–47.CrossRefGoogle ScholarPubMed
67Labbe, G, Descatoire, V, Beaune, Ph, et al. Suicide inactivation of cytochrome p 450 by methoxalen. Evidence for the covalent binding of a reactive intermediate to the protein moiety. J. Pharmacol. Exp. Ther. 1989; 250: 1034–42.Google Scholar
68Loeper, J, Descatoire, V, Letteron, P, et al. Hepatotoxicity of germander in mice. Gastroenterology 1994; 106: 464–72.CrossRefGoogle ScholarPubMed
69Kouzi, SA, McMurty, RJ, Nelson, SD. Hepatotoxicity of germander (Teucrium chamedrys L.) and one of its constituent neoclerodane diterpenes, teucrin A in the mouse. Chem. Res. Toxicol. 1994; 7: 850–6.CrossRefGoogle ScholarPubMed
70Lekehal, M, Pessayre, D, Lereau, JM, Moulis, C, Fourasté, I, Fau, D.Hepatotoxicity of the herbal medicine, germander. Metabolic activation of its furano diterpenoids by cytochrome P450 3A depletes cytoskeleton-associated protein thiols and forms plasma membrane blebs in rat hepatocytes. Hepatology 1996; 24: 212–18.CrossRefGoogle ScholarPubMed
71Fau, D, Lekehal, M, Farrell, G, et al. Diterpenoids from germander, an herbal medicine, induce apoptosis in isolated rat hepatocytes. Gastroenterology 1997; 113: 1334–46.CrossRefGoogle ScholarPubMed
72Mattei, A, Rucay, P, Samuel, D.Liver transplantation for severe acute liver failure after herbal medicine (Teucrium polium) administration. J. Hepatol. 1995; 22: 597.CrossRefGoogle ScholarPubMed
73Sheikh, NM, Philen, RM, Love, LA. Chaparral-associated hepatotoxicity. Arch. Intern. Med. 1997; 157: 913–19.CrossRefGoogle ScholarPubMed
74Kassler, WJ, Blanc, P, Greenblatt, R.The use of medicinal herbs by human immunodeficiency virus-infected patients. Arch. Intern. Med. 1991; 2281–8.CrossRefGoogle ScholarPubMed
75Gordon, DF, Rosenthal, G, Hart, J, Sirota, R, Baker, AL. Chaparral ingestion: the broadening spectrum of liver injury caused by herbal medications. JAMA 1995; 273: 489–90.CrossRefGoogle ScholarPubMed
76Katz, M, Saibil, F.Herbal hepatitis: subacute hepatic necrosis secondary to chaparral leaf. J. Clin. Gastroenterol. 1990; 12: 203–6.CrossRefGoogle ScholarPubMed
77Capdevila, J, Gil, L, Orellana, M.Inhibitors of cytochrome P-450-dependent arachidonic acid metabolism. Arch. Biochem. Biophys. 1988; 261: 257–63.CrossRefGoogle ScholarPubMed
78Agarwal, R, Wang, ZY, Bik, DP, Mukhtar, H.Nordihydroguaiaretic acid, an inhibitor of lipoxygenase, also inhibits cytochrome P-450-mediated monooxygenase activity in rat epidermal and hepatic microsomes. Drug Metab. Dispos. 1991; 19: 620–4.Google ScholarPubMed
79Obermeyer, WR, Musser, SM, Betz, JM, Casey, RE, Pohland, AE, Page, SW. Chemical studies of phytoestrogens in flax and chaparral (43824). Proc. Soc. Exp. Biol. Med. 1995; 208: 6–12.CrossRefGoogle Scholar
80Alderman, S, Kailas, S, Goldfarb, S, Singaram, C, Malone, DG. Cholestatic hepatitis after ingestion of chaparral leaf: confirmation by endoscopic retrograde cholangiopancreatography and liver biopsy. J. Clin. Gastroenterol. 1994; 19: 242–7.CrossRefGoogle ScholarPubMed
81Obatomi, DK, Brant, S, Anthony-Pillai, V, Bach, PH. Toxicity of atractylosides in precision-cut rat and porcine renal and hepatic tissue slices. Toxicol. Appl. Pharmacol. 1998; 148: 35–45.CrossRefGoogle ScholarPubMed
82Mokhobo, KP. Herb use and necro-degenerative hepatitis. S. Afr. Med. J. 1976; 50: 1096–9.Google ScholarPubMed
83Beuers, U, Spengler, U, Pape, G.Hepatitis after chronic abuse of senna. Lancet 337; 2: 372–3.Google Scholar
84Popper, H, Rubin, E, Gardiol, D, Schaffner, F, Paronetto, F.Drug-induced liver disease: a penalty for progress. Arch. Intern. Med. 1965; 115: 128–36.CrossRefGoogle Scholar
85Colin-Jones, DG, Harvey, J.Mistletoe hepatitis. BMJ 1982; 284: 744.CrossRefGoogle Scholar
86McGregor, FB, Abernethy, VE, Dahabra, S, Cobden, I, Hayes, PC. Hepatotoxicity of herbal remedies. BMJ 1989; 299: 1156–7.CrossRefGoogle Scholar
87Mullins, ME, Horowitz, BZ. The case of the salad shooters: intravenous injection of wild lettuce extract. Vet. Hum. Toxicol. 1998; 40: 290–1.Google ScholarPubMed
88Hamid, S, Rojter, S, Vierling, J.Protracted cholestatic hepatitis after the use of prostata. Ann. Intern. Med. 1997; 127: 169.CrossRefGoogle ScholarPubMed
89Anderson, IB, Mullen, WH, Meeker, JE, et al. Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature. Ann. Intern. Med. 1996; 124: 726–34.CrossRefGoogle ScholarPubMed
90Gordon, WP, Huitric, AC, Seth, CL, McClanahan, RH, Nelson, SD. The metabolism of the abortifacient terpene, (R)-(+)-pulegone, to a proximate toxin, menthofuran. Drug Metab. Dispos. 1987; 15: 589–94.Google Scholar
91Thomassen, D, Slattery, JT, Nelson, SD. Menthofuran-dependent and independent aspects of pulegone hepatotoxicity: roles of glutathione. J. Pharmacol. Exp. Ther. 1990; 253: 567–72.Google ScholarPubMed
92Thomassen, D, Knebel, N, Slattery, X, McClanahan, RH, Nelson, SD. Reactive intermediates in the oxidation of menthofuran by cytochromes P-450. Chem. Res. Toxicol. 1992; 5: 123–30.CrossRefGoogle ScholarPubMed
93Jacobs, J, Von Behren, J, Kreuzer, R.Serious mushroom poisoning in California requiring hospital admission, 1990 through 1994. West. J. Med. 1990; 165: 283–7.Google Scholar
94Litowitz, TL, Clark, LR, Soloway, RA. 1993 annual report of the American Association of Poison Control Centers toxic exposures surveillance system. Am. J. Emerg. Med. 1994; 12: 546–84.CrossRefGoogle Scholar
95McPartland, JM, Vilogalys, RJ, Cubeta, MA. Mushroom poisoning. Am. Fam. Physician 1997; 55: 1797–800, 1805–9, 1811–12.Google ScholarPubMed
96Wieland, O.Changes in liver metabolism induced by the poisons of Amanita phalloides. Clin. Chem. 1965; 11: 323–38.Google ScholarPubMed
97Bartolini, ST, Omer, F, Giannini, A.Amanita poisoning: a clinical–histopathological study of 64 cases of intoxication. Hepatogastroenterology 1985; 32: 229–31.Google Scholar
98Chang, IM, Yon, HS, Kim, YX, Ahn, JW. Aucubin: potential antidote for alpha-amanitin poisoning. J. Toxicol. Clin. Toxicol. 1984; 22: 77–85.CrossRefGoogle ScholarPubMed
99Kroncke, KD, Fricker, G, Meier, PJ, Gerok, W, Wieland, T, Kurz, G.Alpha-amanitin uptake into hepatocytes. J. Biol. Chem. 1986; 261: 12562–7.CrossRefGoogle ScholarPubMed
100Faulstich, H.Analysis of toxins of Amanita-containing mushrooms. Z. Naturforsch. 1974; 29: 86–8.CrossRefGoogle ScholarPubMed
101Faulstich, H, Talas, A, Wellnoner, HH. Toxicokinetics of labelled amatoxins in the dog. Arch. Toxicol. 1985; 56: 190–4.CrossRefGoogle ScholarPubMed
102Passo, B, Harrison, CD. A new look at an old problem: mushroom poisoning. Am. J. Med. 1975; 58: 505–9.CrossRefGoogle Scholar
103Faulstich, H.New aspects of Amanita poisoning. Klin. Wochenschr. 1979; 57: 1143–52.CrossRefGoogle ScholarPubMed
104Becker, CE, Tong, TG, Boerner, U.Diagnosis and treatment of Amanita-phalloides-type mushroom poisoning. West. J. Med. 1976; 125: 100–9.Google ScholarPubMed
105Klein, AS, Hart, J, Brems, JJ. Amanita poisoning: treatment and the role of liver transplantation. Am. J. Med. 1989; 86: 187–93.CrossRefGoogle ScholarPubMed
106Floersheim, GL. Treatment of human amatoxin poisoning: myths and advances in therapy. Med. Toxicol. Adverse Drug. Exp. 1987; 2: 1–9.Google ScholarPubMed
107Wauters, JP, Rossel, C, Farguet, JJ. Amanita phalloides poisoning treated by early charcoal hemoperfusion. BMJ 1978; 11: 1465.CrossRefGoogle Scholar
108Floersheim, GL. Curative properties against alpha-amanita poisoning by cytochrome C. Science 1972; 177: 800–9.CrossRefGoogle Scholar
109Floersheim, GL, Eberhard, M, Tschumi, P, Duckert, F.Effects of penicillin and silymarin on liver enzymes and blood clotting factors in dogs given a boiled preparation of Amanita phalloides. Toxicol. Appl. Pharmacol. 1978; 46: 455–62.CrossRefGoogle Scholar
110Floersheim, GL, Weber, O, Tschumi, P, Ulbrich, M.Die klinische Knollenblaetterpilzvergiftung: Prognostische Faktoren und therapeutische Massnahmen. Schweiz. Med. Wochenschr. 1982; 112: 1164–77.Google Scholar
111Marshall, AW, Gravl, RS, Morgan, MY, Sherlock, S.Treatment of alcohol-related liver disease with thioctic acid: a six months randomized double-blind trial. Gut 1982; 23: 1088–93.CrossRefGoogle Scholar
112Beckurts, KTE, Hoelscher, AH, Heidecke, CD, Zilker, TR, Natrath, W, Siewert, JR. The place of liver transplantation in the treatment of acute liver failure caused by Amanita phalloides poisoning. Dtsch. Med. Wochenschr. 1997; 122: 351–5.CrossRefGoogle Scholar