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Toxicity of pyrrolizidine alkaloids - a serious health problem

Yıl 2011, Cilt: 1 Sayı: 2, 79 - 87, 31.01.2014

Helmut Wiedenfeld

Öz

Pyrrolizidine alkaloids (PAs) are toxic for human and livestock. The PAs undergo a metabolic toxication process in the liver which is the first target organ for PA poisoning. World-wide many incidents of PA intoxications in humans have been reported. This intoxication is not only related to the amount and duration of the exposure but also to age and gender. Besides the metabolic toxication, detoxication processes are also important. The paper discusses the toxication and detoxication processes and gives an overview about PA poisoning cases in humans.

Key words: Pyrrolizidine alkaloids, metabolic toxication; detoxication; poisoning in humans 

Anahtar Kelimeler

-

Kaynakça

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  • Gilruth JA. Hepatic cirrhosis due to ragwort (Senecio jacobaea). Div. Vet. Sci. New Zealand, Dept. Agric., Bull. 1904; No. 9. 252-254.
  • Bull LB, Dick AT. The chronic pathological effects on the liverof the rat of the pyrrolizidine alkaloids heliotrine, lasiocarpine, and their N-oxides. J. Pathol. Bacteriol. 1959; 78: 483-502.
  • Willmott FC, Robertson GW. Senecio disease or cirrhosis of the liver due to Senecio poisoning. Lancet 1920; 23 October: 848-849.
  • Steyn DG. Poisoning of human beings by weeds contained in cereals (bread poisoning). Onderstepoort J. Vet Sci Anim. Ind. 1933; 1: 219-266.
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  • Milenkov SM, Kizhaikin Y. Toxic hepatitis with ascites. Proc. Sympos. V. M. Molotov Med. Inst., Tashkent. 1952.
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  • Mohabbat O, Srivastava RN, Younos MS, Sediq GG, Menzad AA, Aram GN. An outbreak of hepatic veno-occlusive disease in north-western Afghanistan. Lancet 1976; 7 August: 269-271.
  • Chauvin P, Dillon J-C., Moren A. (1994) Épidémie d’ intoxication alimentaire á l’ héliotrope, Tadjikistan, Novembre 1992-Mars 1993. Cahiers Santé 4: 263- 268.
  • Chauvin P., Dillon J-C, Moreu A, Talbak S, Barakaev S. Heliotrope poisoning in Tadjikistan. Lancet 1993; 341: 1633.
  • Mayer F, Lüthy J. Heliotrope poisoning in Tadjikistan. Lancet 1993; 342: 246-247.
  • International Programme on Chemical Safety.(IPCS) Pyrrolizidine Alkaloids Health and Safety Guide. Health and Safety Guide No. 26. Geneva: WHO, 1989.
  • Roeder E. Medicinal plants in Europe containing pyrrolizidine alkaloids. Pharmazie 1995; 50: 83-98.
  • Roeder E. Medicinal plants in China containing pyrrolizidine alkaloids. Pharmazie 2000; 55: 711-726.
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Pirolizidin alkaloidlerin toksisitesi - ciddi bir sağlık problemi

Yıl 2011, Cilt: 1 Sayı: 2, 79 - 87, 31.01.2014

Helmut Wiedenfeld

Öz

Pirolizidin alkaloidleri (PA) insanlar ve çiflik hayvanları için toksiktir. Karaciğer, PA’ların toksik etkiyi gösterdikleri ilk hedef organdır ve burada metabolik toksikasyon işlemi başlar. Dünya çapında, insanlarda PA intoksikasyonları rapor edilmiştir. Bu intoksikasyonlar sadece maruz kalınan miktar ve süreye bağlı değildir. Aynı zamanda yaş ve cinsiyetle de ilişkilidir. Metabolik toksikasyonun yanısıra detoksifikasyon işlemi de önemlidir. Bu çalışma, PA’ların toksikasyonu ve detoksifikasyonu proseslerini tartışmakta ve PA’larla ilgili olarak insanlarda zehirlenme vakaları hakkında genel bilgi vermektedir.

Anahtar Kelimeler : Pirolizidin alkaloidleri,

Anahtar Kelimeler

Pirolizidin alkaloidleri metabolik toksikasyon detoksifikasyon insanlarda zehirlenme

Kaynakça

  • Gilruth JA. Hepatic cirrhosis affecting horses and cattle (so-called “Winton disease”). New Zealand Department of Agriculture, 11th annual report. pp., 1903: 228-279.
  • Gilruth JA. Hepatic cirrhosis due to ragwort (Senecio jacobaea). Div. Vet. Sci. New Zealand, Dept. Agric., Bull. 1904; No. 9. 252-254.
  • Bull LB, Dick AT. The chronic pathological effects on the liverof the rat of the pyrrolizidine alkaloids heliotrine, lasiocarpine, and their N-oxides. J. Pathol. Bacteriol. 1959; 78: 483-502.
  • Willmott FC, Robertson GW. Senecio disease or cirrhosis of the liver due to Senecio poisoning. Lancet 1920; 23 October: 848-849.
  • Steyn DG. Poisoning of human beings by weeds contained in cereals (bread poisoning). Onderstepoort J. Vet Sci Anim. Ind. 1933; 1: 219-266.
  • Bourkser GV. On the question of the aetiology and pathogenesis of toxic hepatitis with ascites (heliotrope toxicosis). Hyg. Sanit.1947; 6: 24-26.
  • Milenkov SM, Kizhaikin Y. Toxic hepatitis with ascites. Proc. Sympos. V. M. Molotov Med. Inst., Tashkent. 1952.
  • Tandon HD, Tandon BN. Epidemic of liver disease – Gulran District, Herat Province, Afghanistan, Alexandria, World Health Organization, Regional Office for the Eastern Mediterranean (Assignment report No. EM/AFG/OCD/001/RB). 1975.
  • Mohabbat O, Srivastava RN, Younos MS, Sediq GG, Menzad AA, Aram GN. An outbreak of hepatic veno-occlusive disease in north-western Afghanistan. Lancet 1976; 7 August: 269-271.
  • Chauvin P, Dillon J-C., Moren A. (1994) Épidémie d’ intoxication alimentaire á l’ héliotrope, Tadjikistan, Novembre 1992-Mars 1993. Cahiers Santé 4: 263- 268.
  • Chauvin P., Dillon J-C, Moreu A, Talbak S, Barakaev S. Heliotrope poisoning in Tadjikistan. Lancet 1993; 341: 1633.
  • Mayer F, Lüthy J. Heliotrope poisoning in Tadjikistan. Lancet 1993; 342: 246-247.
  • International Programme on Chemical Safety.(IPCS) Pyrrolizidine Alkaloids Health and Safety Guide. Health and Safety Guide No. 26. Geneva: WHO, 1989.
  • Roeder E. Medicinal plants in Europe containing pyrrolizidine alkaloids. Pharmazie 1995; 50: 83-98.
  • Roeder E. Medicinal plants in China containing pyrrolizidine alkaloids. Pharmazie 2000; 55: 711-726.
  • Bras G, Jelliffe DB, Stuart KL. Veno-occlusive disease of liver with nonportal type of cirrhosis, occurring in Jamaica. Arch. Pathol. 1954; 57: 285-300.
  • Bras G, Brooks SEH, Watler DC. Cirrhosis ofLiver in Jamaica. J. Pathol. Bacteriol. 1961; 82: 503-11.
  • FDA. FDA Advises Dietary Supplement Manufacturers to Remove Comfrey Products From the Market. 2001.
  • EFSA. Opinion of the Scientific Panel on contaminants in the Food Chain of the European Food Safety Authority (EFSA) on a request from the European Commission related to pyrrolizidine alkaloids as undesirable substances in animal feed. EFSA J. 2007; 447:1-51.
  • Bundesanzeiger, June 17, 4805; cited by: Dtsch. Apoth. Ztg. 1992; 132, 1406-1408.
  • Bundesgesetzblatt Verordnung des Bundesministers für Gesundheit und öffentlicher Dienst vom 5. Mai 1989 betreffend Arzneimittel, die nicht in Verkehr gebracht werden dürfen. 555/1994 Wien, Österreich.
  • Staatsblaad Besluit van 19 januari 2001, houdende vaststelling van het Warenwetbesluit Kruidenpreparaten. Staatsblad van het Koninkrijk der Nederlanden. 2001; 56:1–12.
  • Schoental R. The chemical aspects of seneciosis. Proc. Roy. Soc. Med. 1959; 53: 284-288.
  • Dickinson J.O, Cooke MP, King RR, Mohamed PA. Milk transfer of pyrrolizidine alkaloids in cattle. J. Am. Vet. Med. Assoc. 1976; 169: 1192-1196.
  • Dickinson JO. Release of pyrrolizidine alkaloids into milk. Proc. West. Pharmacol. Soc. 1980; 23: 377-379.
  • Johnson WD, Robertson KA, Pounds JG, Allen JR. Dehydroretronecine- induced skin tumours in mice. J. Natl. Cancer Inst. 1978; 61: 85-89.
  • Goeger DE, Cheeke PR, Schmitz JA, Buhler DR. Toxicity of tansy ragwort (Senecio jacobaea) to goats. Am. J. Vet. Res. 1982; 43: 252-254.
  • Lüthy J, Heim TH, Schlatter CH. Transfer of [3H] pyrrolizidine alkaloids from Senecio vulgaris L. and metabolites into rat milk and tissues. Toxicol. Lett. 1983; 17: 283-288.
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  • Mattocks AR, White INH. The conversion of pyrrolizidine alkaloids to dihydropyrrolizine derivatives by rat-liver microsomes in vitro. Chem. Biol. Interact. 1971; 3: 383-396.
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  • Coulombe RA, Drew GL, Stermitz FR. Pyrrolizidine alkaloids crosslink DNA with actin. Toxicol. Appl. Pharmacol. 1999; 154:198-202.
  • Yan J, Nichols J, Yang Y-C, Fu PP. Detection of riddelliine-derived DNA adducts in blood of rats fed riddelliine. Int. J. Mol. Sci. 2002; 3: 1019- 26.
  • Fu PP, Xia Q, Lin G, Chou MW. Genotoxic pyrrolizidine alkaloids mechanisms leading to DNA adduct formation and tumorigenicity. Int. J. Mol. Sci. 2002; 3:948-64.
  • Fu PP, Xia Q, Lin G. Pyrrolizidine alkaloids – genotoxicity, metabolism enzymes, metabolic activation, and mechanism. Drug Metabol. Revs. 2004; 36: 1-55.
  • Xia Q, Chou MW, Edgar JA, Doerge DR, Fu PP. Formation of DHP- derived DNA adducts from metabolic activation of the prototype heliotridine-type pyrrolizidine alkaloid, lasiocarpine. Cancer Lett.
  • Mattocks AR. Chemistry and Toxicology of Pyrrolizidine Alkaloids, London, New Yorck, Academic Express. 1986.
  • Cheeke PR, Gorman GR. Influence of dietary protein and sulphur amino-acid levels on the toxicity of Senecio jacobaea (tansy ragwort) to rats. Nutr. Rep. Int. 1974; 9: 197-207.
  • Nigra L, Huxtable RJ. Hepatic glutathione concentrations and the release of pyrrolic metabolites of the pyrrolizidine alkaloid, monocrotaline, from the isolated perfused liver. Toxicon 1992; 30: 1195-1202.
  • Reed RL, Miranda CL, Kedzierski B, Henderson MC, Buhler DR. Microsomal formation of a pyrrolic alcohol glutathione conjugate of the pyrrolizidine alkaloid senecionine. Xenobiotica 1992; 1: 1321-1327.
  • Peterson JE, Jago MV. Comparison of the toxic effects of dehydroheliotridine and heliotrine in pregnant rats and their embryos. J. Pathol. 1980; 131: 339-355.
  • Robertson KA. Alkylation of N2 in deoxyguanosine by dehydroretronecine, a carcinogenic metabolite of the pyrrolizidine alkaloid monocrotaline. Cancer Res. 1982; 42: 8-14.
  • Peterson JE, Samuel A, Jago MV. Pathological effects ofdehydroheliotridine, a metabolite of heliotridine-based pyrrolizidinealkaloids in the young rat. J. Pathol. 1972; 107: 107-189.
  • Prakash AR, Pereira TN, Reilly PEB, Seawright AA. (1999) Pyrrolizidine alkaloids in human diet. Mutation Res. 1999; 443: 53-67.
  • Allen JR, Hsu I-C, Carstens LA. (1975) Dehydroretronecine induced rhabdomyosarcomas in rats. Cancer Res. 1975; 35: 997–1002.
  • Shumaker RC, Robertson KA, Hsu IC, Allen JR. Neoplastic transformation in tissues of rats exposed to monocrotaline or dehydroretronecine. J. Natl. Cancer Inst. 1976; 56: 787-789.
  • Mattocks AR, Cabral JRP. Carcinogenicity of some pyrrolizidine alkaloid metabolites and analogues. Cancer Lett. 1982; 17: 61-66.
  • Peterson JE, Culvenor CCJ. Plant and fungal toxins. In: Keeler, R.F. & Tu, A.T., ed. Handbook of natural toxins, New York, Marcel Dekker, Vol. 1. 1983; pp. 637-681.
  • Culvenor CCJ, Edgar JA, Jago MV, Outteridge A, Peterson JE, Smith LW. (1976) Hepato- and pneumotoxicity of pyrrolizidine alkaloids and derivatives in relation to molecular structure. Chem.-Biol. Interact. 1976; 12: 299-324.
  • Williams DE, Reed RL, Kedziersk B, Dannan GA, Guengerich FP, Buhler DR. Bioactivation and detoxication of the pyrrolizidine alkaloid senecionine by cytochrome P-450 enzymes in rat liver. Drug Metab. Dispos. 1989; 17: 387-392.
  • Miranda CL, Chung W, Reed RE, Zhao X, Henderson MC, Wang JL, Williams DE, Buhler DR. Flavin-containing monooxygenase: a major detoxifying nzyme for the pyrrolizidine alkaloid senecionine in guinea pig tissues. Biochem. Biophys. Res. Commun. 1991; 178: 546-552.
  • McLean EK. The toxic actions of pyrrolizidine (Senecio) alkaloids. Pharmacol. Rev. 1970; 22: 429-483.
  • Huxtable RJ. Human health implications of pyrrolizidine alkaloids and herbs containing them. In: Cheeke PR, ed. Toxicants of Plant Origin, Vol 1. 1989; pp. 42-86 Boca Raton: CRC Press.
  • Stegelmeier BL, Edgar JA, Steven M, Colegate SM, Gardner DR, Schoch TK, Coulombe RA jr. Pyrrolizidine alkaloids plants, metabolism and toxicity. J. Nat. Toxins 1999; 8: 5-116.
  • Rasenack R, Müller C, Kleinschmidt M, Rasenack J, Wiedenfeld H. Veno-occlusive disease in a foetus caused by pyrrolizidine alkaloids of food origin. Fetal Diagn. Ther. 2003; 18: 223-25.
  • Yee SB, Kinser S, Hill DA, Barton CC, Hotchkiss JA, Harkema JR, Ganey PE, Roth RA. Synergistic hepatotoxicity from coexposure to bacterial endotoxin and the pyrrolizidine alkaloid monocrotaline. Toxicol. Appl. Pharmacol. 2000; 166: 173-185.
  • Newberne .M, Rogers AE. Nutrition, monocrotaline and aflatoxin B1 in liver carcinogenesis. Plant Food Man. 1973; 1: 23-31.
  • White INH, Mattocks AR, Butler WH. The conversion of thepyrrolizidine alkaloid retrorsine to pyrrolic derivatives in vivo andin vitro and its acute toxicity to various animal species.Chem. Biol. Interact. 1973; 6: 207-218.
  • Tuchweber B, Kovacs K, Jago MV, Beaulieu T. (1974) Effect of steroidal and nonsteroidal microsomal enzyme inducers on the hepatotoxicity of pyrrolizidine alkaloids in rats. Res. Commun. Chem. Pathol. Pharmacol. 1974; 7: 459-480.
  • Lin JJ, Liu C, Svoboda DJ. (1974) Long-term effects of aflatoxin B1 and vocal hepatitis on marmoset liver: a preliminary report. Lab. Invest. 1974; 30: 267-278.
  • Bull LB, Culvenor CCJ, Dick AT. The pyrrolizidine alkaloids, Amsterdam, 1968; North Holland Publishing Co.
  • Freiman I, Schmaman A, Zamit R, Appleberg M. Veno-occlusive disease of the liver – some new aspects. S. Afr. Med. J. 1968; 42: 126-129.
  • Grases PJ, Beker SG. Veno-Occlusive Disease of the Liver – A Case from Venezuela. Am. J. Med. 1972; 53: 511-16.
  • Macksad A, Schoental R, Coady A. The Hepatotoxic Action of a Traditionl Bedu Plant Remedy “Ramram”. J. Kwt. Med. Assoc. 1970; 4: 297-299.
  • Brooks SEH, Miller CG, McKenzie K, Audretsch JJ, Bras G. Acute Veno- occlusive Disease of the Liver. Arch. Path. 1970; 89: 507-520.
  • Al-Hasany M, Mohamed AS. Veno-occlusive of the Liver in Iraq. Arch. Dis. Childhood 1970; 45: 722-24.
  • Tandon BN, Tandon RK, Tandon HD, Narndranathan M, Joshi JK. An Epidemic Veno-Occlusive Disease of Liver in Central India. Lancet 1976; 7 August: 271-72.
  • Lyford CL, Vergara GG, Moeller DD. Hepativ Veno-Occlusive Disease Originating in Ecuador. Gastroenterology 1976; 70: 105-8.
  • Krishnamachari KAVR, Bhat RV, Krishnamurthi D, Krishnaswamy K, Nagarajan V. Aethiopathogenesis of endemic ascites in Surguja district of Madhya Pradesh. Indian J. Med. Res. 1977; 65: 672-78.
  • Hou JG, Xia YT, Yu CS, An Y, Tang YH. Veno-occlusive disease of the liver –with two fatal cases. Zhongua Neike Zazhi 1980; 19: 187-191.
  • Datta DV, Khuroo MS, Mattocks AR, Aikat BK, Chhuttani PN. Herbal medicines and veno-occlusive disease in India. Postgraduate Medical Journal 1878; 54: 511-15.
  • Saint-Aimé MM, Ponsar C, Lacombe C, Lacombe W. Maladie Veino- Occlusive du Foie chez L´Enfant Martiniquais. Bordeaux Médical
  • Stillman AE, Huxtable RJ, Fox DW, Hart MC, Bergeson PS, Counts JM. Poisoning associated with Herbal Teas –Arizona, Washington. Morbidity and Mortality Weekly Report 1977; 26: 257-59.
  • McGee JO, Patrick RS, Wood CB, Blumgart LH. A case of veno- occlusive disease of theliver in Britain associated with herbal tea consumption. J. Clin. Path. 1976; 29: 788-794.
  • Ridker PM, Ohkuma S, McDermott WV, Trey C, Huxtable RJ. Hepatic veno-occlusive disease associated with consumption of pyrrolizidine alkaloid containing dietary supplements. Gastroenterology 1985; 88: 1050-1054.
  • Culvenor CCJ, Edgar JA, Smith LW, Kumana CR, Lin HJ. Lancet 1986; 26 April: 978.
  • Margalith D, Heraief C, Schindler AM, Birchler R, Mosimann F, Aladjem D, Gonvers JJ. Veno-occlusive disease of the liver due to the se of tea made from Senecio plants. J. Hepatol. 1985; Suppl., 280.
  • Weston CFM, Cooper BT, Davies JD, Levine DF. Veno-occlusive disease of the liver secondary to ingestion of comfrey. Brit. Med. J. 1987; 295: 183.
  • Tomioka M, Calvo F, Siguas A, Sanchez L, Nava E, Garcia U, Valdivia M, Reategui E. Enfermedad hepatica veno-oclusiva asociada a l ingestion de humanrripa (Senecio tephrosioides). Rev. Gastroenterol. Peru 1995; 15: 299-302.
  • Cansado AO, Valades EC, Blanco PM, de Santamaria JS, Gonsalez JM, Téllez TR. Enfermedad venooclusiva hepatica por ingestion de infusiones de Senecio vulgaris. Gastroenterolog. Hepatol. 1995; 18: 413-416.
  • Sperl W, Stuppner H, Gassner I, Judmaier W, Dietze O, Vogel W. Reversible hepatic veno-occlusive disease in an infant after consumption of pyrrolizidine-containing herbal tea. Eur. J. Pedriatr. 1995; 154: 112-116.
  • Vilar JH, Garcia M, Cabrera P. Enfermedad venooclusiva hepática de causa Tóxica por Senecio vulgaris. Gastroenterol. Hepatol. 2000; 23: 285-6.
Toplam 112 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Articles
Yazarlar

Helmut Wiedenfeld Bu kişi benim

Yayımlanma Tarihi 31 Ocak 2014
Gönderilme Tarihi 2 Kasım 2013
Yayımlandığı Sayı Yıl 2011 Cilt: 1 Sayı: 2

Kaynak Göster

APA Wiedenfeld, H. (2014). Pirolizidin alkaloidlerin toksisitesi - ciddi bir sağlık problemi. Clinical and Experimental Health Sciences, 1(2), 79-87.
AMA Wiedenfeld H. Pirolizidin alkaloidlerin toksisitesi - ciddi bir sağlık problemi. Clinical and Experimental Health Sciences. Ocak 2014;1(2):79-87.
Chicago Wiedenfeld, Helmut. “Pirolizidin Alkaloidlerin Toksisitesi - Ciddi Bir sağlık Problemi”. Clinical and Experimental Health Sciences 1, sy. 2 (Ocak 2014): 79-87.
EndNote Wiedenfeld H (01 Ocak 2014) Pirolizidin alkaloidlerin toksisitesi - ciddi bir sağlık problemi. Clinical and Experimental Health Sciences 1 2 79–87.
IEEE H. Wiedenfeld, “Pirolizidin alkaloidlerin toksisitesi - ciddi bir sağlık problemi”, Clinical and Experimental Health Sciences, c. 1, sy. 2, ss. 79–87, 2014.
ISNAD Wiedenfeld, Helmut. “Pirolizidin Alkaloidlerin Toksisitesi - Ciddi Bir sağlık Problemi”. Clinical and Experimental Health Sciences 1/2 (Ocak 2014), 79-87.
JAMA Wiedenfeld H. Pirolizidin alkaloidlerin toksisitesi - ciddi bir sağlık problemi. Clinical and Experimental Health Sciences. 2014;1:79–87.
MLA Wiedenfeld, Helmut. “Pirolizidin Alkaloidlerin Toksisitesi - Ciddi Bir sağlık Problemi”. Clinical and Experimental Health Sciences, c. 1, sy. 2, 2014, ss. 79-87.
Vancouver Wiedenfeld H. Pirolizidin alkaloidlerin toksisitesi - ciddi bir sağlık problemi. Clinical and Experimental Health Sciences. 2014;1(2):79-87.

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