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Tierarztl Prax Ausg G Grosstiere Nutztiere 2011; 39(06): 363-372
DOI: 10.1055/s-0038-1623090
Übersichtsartikel
Schattauer GmbH

Pyrrolizidinalkaloide und die Seneciose bei Tieren

Teil 2: Klinik, Speziesunterschiede, Rückstandsverhalten, Futtermittelkontamination und GrenzwertePyrrolizidine alkaloids and seneciosis in farm animals. Part 2: Clinical signs, species-specific sensitivity, food residues, feed contamination, limit values
E. Petzinger
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Publikationsverlauf

Eingegangen: 15. März 2011

Akzeptiert nach Revision: 17. Juni 2011

Publikationsdatum:
10. Januar 2018 (online)

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Zusammenfassung

Im Vordergrund der Vergiftungen mit Pyrrolizidinalkaloiden (PA) steht die chronische Toxinaufnahme durch Verzehr kontaminierten Heus, die zu Leberschäden in Form einer letal verlaufenden Leberzirrhose bzw. einer venenokklusiven Erkrankung in Leber und Lunge führen kann. Die Vergiftungssymptomatik ist nicht bei allen Tierspezies identisch und bezieht auch zentralnervöse Störungen mit ein. Bei betroffenen Pferden werden deutlich erhöhte Serumwerte hepatogener Enzyme und eine verzögerte Bromsulphthalein-Retentionszeit als Indikatoren für einen fatalen Krankheitsverlauf gewertet. Die chronische Seneciose des Pferdes ist unheilbar. Kaninchen, Japanische Wachteln und Meerschweinchen gelten als vergiftungsresistent. Schafe und besonders Ziegen erweisen sich als so unempfindlich, dass nur nach Aufnahme extremer Pflanzenmengen, die das eigene Körpergewicht um ein Mehrfaches übersteigen, Giftwirkungen auftreten. Dagegen sind Schweine, Rinder und Pferde sowie Hühner und ebenso der Mensch gegenüber Vergiftungen mit PA-haltigen Pflanzen sehr empfindlich. Bei empfindlichen Tierspezies genügen sehr geringe Mengen an getrocknetem kontaminiertem Heu, um die als unbedenklich für den Menschen angesehene tägliche PA-Aufnahmemenge von 1 μg/kg KM zu überschreiten. Damit sind die Futtermittel, in denen erkennbare Pflanzenteile an Jakobskreuzkraut vorkommen, von der Verfütterung auszuschließen bzw. zu vernichten.

Summary

At the forefront of pyrrolizidine alkaloid (PA) poisoning is the chronic ingestion of contaminated hay, which causes liver damage resulting in an ongoing fatal liver cirrhosis or in the veno-occlusive disease in liver or lung, respectively. The symptomatology of PA-poisoning is not identical for all animal species, and also includes central nervous symptoms. In affected horses significantly elevated levels of hepatogenic serum enzymes and an increase of the retention time for bromosulfophthalein indicates the fatal outcome of the intoxication. Chronic seneciosis of horses is incurable. Rabbits, Japanese quails, and guinea pigs are regarded as poison-resistant species. Sheep and in particular goats are insensitive unless extremely high amounts of plants which exceed the animal’s body weight by several-fold are ingested. In contrast, pigs, cattle, and horses as well as chicken and likewise man are very sensitive to poisonings by PA-containing plants. In sensitive animal species a very small amount of contaminated dry hay is needed to exceed the daily dose of 1 μg/kg body weight PA which is taken as harmless for man by health authorities. Therefore, all feed with visible pieces of Senecio jacobaea plants are not acceptable as animal fodder and should be destroyed.

Schlüsselwörter

Jakobskreuzkraut - Schweinsberger Krankheit - Leberzirrhose - venenokklusive Erkrankung - Toxinresistenz - Lebensmittelrückstände - Futtermittelsicherheit

Key words

Liver cirrhosis - veno-occlusive disease - toxin resistance - food residues - feed safety
 

  • Literatur

  • 1 ANZFA (Australia New Zealand Food Authority (2001) Pyrrolizidine alkaloids in food. A toxicological review and risk assessment. http://www.anzfa.gov.au.
    PubMedGoogle Scholar
  • 2 BfR (Bundesinstitut für Risikobewertung). Salatmischung mit Pyrrolizidinalkaloid-haltigem Greiskraut verunreinigt. Stellungnahme Nr. 028/2007 vom 10. Januar 2007 http://www.bfr.bund.de/cm/208/salatmischung_mit_pyrrolizidinalkaloid_haltigem_geiskraut_verunreinigt.pdf.
    PubMedGoogle Scholar
  • 3 BGA (Bundesgesundheitsamt): Abwehr von Arzneimittelrisiken. Stufe II. Pyrrolizidinhaltige Humanarzneimittel. 10.08.1988; Az: GV 7–7251–01– 25365.
    PubMedGoogle Scholar
  • 4 BGA (Bundesgesundsheitsamt): Abwehr von Arzneimittelrisiken. Stufe II; Bundesanzeiger. 17.06.1992 111: 4805.
    PubMedGoogle Scholar
  • 5 Brink NG. Somatic and teratogenic effects induced by heliotrine in drosophila. Mut Res 1982; 104: 105-111.
    CrossrefPubMedGoogle Scholar
  • 6 Buckmaster GW, Cheeke PR, Shull LR. Pyrrolidine alkaloid poisoning in rats: protective effects of dietary cysteine. J Anim Sci 1976; 43: 464-473.
    CrossrefPubMedGoogle Scholar
  • 7 Buckmaster GW, Cheeke PR, Arscott GH, Dickinson EO, Pierson ML, Shull LR. Response of Japanese quail to dietary and injected pyrrolizidine (Senecio) alkaloids. J Anim Sci 1977; 45: 1322-1325.
    CrossrefPubMedGoogle Scholar
  • 8 Candrian U, Lüthy J, Schmid P, Schlatter CH, Gallasz E. Stability of pyrrolizidine alkaloids in hay and silage. J Agric Food Chem 1984; 32: 935-937.
    CrossrefPubMedGoogle Scholar
  • 9 Chan PC, Mahler J, Bucher JR, Travlos GS, Reid JB. Toxicity and carcinogenicity of riddelliine following 13 weeks of treatment to rats and mice. Toxicon 1994; 32: 891-908.
    CrossrefPubMedGoogle Scholar
  • 10 Cheeke PR, Garman GR. Influence of dietary protein and sulphur amino acid levels on the toxicity of Senecioa jacobaea (tansy ragwort) to rats. Nutr Report Internat 1974; 9: 197-207.
    PubMedGoogle Scholar
  • 11 Cheeke PR, Schmitz JA, Lassen ED, Pearson EG. Effects of dietary supplementation with ethoxyquin, magnesium oxide, methionine hydroxy analog, and B vitamins on tansy ragwort (Senecio jacobaea) toxicosis in beef cattle. Am J Vet Res 1985; 46: 2179-2183.
    PubMedGoogle Scholar
  • 12 Cheeke PR. Toxicity and metabolism of pyrrolizidine alkaloids. J Anim Sci 1988; 66: 2343-2350.
    CrossrefPubMedGoogle Scholar
  • 13 Chung WG, Buhler DR. Major factors for the susceptibility of guinea pig to the pyrrolizidine alkaloid jacobine. Drug Metabol Disp 1995; 23: 1263-1267.
    PubMedGoogle Scholar
  • 14 Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. COT statement on pyrrolizidine alkaloids in food. Food Standard Agency; 2008
    Google Scholar
  • 15 Crews C, Berthiller F, Krska R. Update on analytical methods for toxic pyrroli zidine alkaloids. Anal Bioanal Chem 2010; 396: 327-338.
    CrossrefPubMedGoogle Scholar
  • 16 Curran JM, Sutherland RJ, Peet RL. A screening test for subclinical liver disease in horses affected by pyrrolizidine alkaloid toxicosis. Aust Vet J 1996; 74: 236-240.
    CrossrefPubMedGoogle Scholar
  • 17 Dickinson JO, Cooke MP, King RR, Mohamed PA. Milk transfer of pyrrolizidine alkaloids in cattle. J Am Vet Med Assoc 1976; 169: 1192-1196.
    PubMedGoogle Scholar
  • 18 Dunlop RH, Malbert C-H. eds. Part 2: Pathophysiology of plant toxicants. In: Veterinary Pathophysiology. Ames, Iowa: Blackwell; 2004: 490-499.
    Google Scholar
  • 19 EFSA. Opinion of the Scientific Panel on Contaminants in the food chain on a request from the European Commission related to pyrrolizidine alkaloids as undesirable substances in animal feed. EFSA J 2007; 447: 1-51.
    PubMedGoogle Scholar
  • 20 Fowler ME. Pyrrolizidine alkaloid poisoning in calves. J Am Vet Med Assoc 1968; 152: 1131-1137.
    PubMedGoogle Scholar
  • 21 Fu PP, Xia N, Lin G, Chou MW. Pyrrolizidine alkaloids – Genotoxicity, metabolism enzymes, metabolic activation, and mechanisms. Drug Metabol Rev 2004; 36: 1-55.
    PubMedGoogle Scholar
  • 22 Garrett BJ, Holtan DW, Cheeke PR, Schmitz JA, Rogers QR. Effects of dietary supplementation with butylated hydroxyanisole, cysteine, and vitamin B on tansy ragwort (Senecio jacobaea) toxicosis in ponies. Am J Vet Res 1984; 45: 459-464.
    PubMedGoogle Scholar
  • 23 Giles CJ. Outbreak of ragwort (Senecio jacobaea) poisoning in horses. Equine Vet J 1983; 15: 248-250.
    CrossrefPubMedGoogle Scholar
  • 24 Goeger DE, Cheeke PR, Schmitz JA, Buhler DR. Toxicity of tansy ragwort (Senecio jacobaea) to goats. Am J Vet Res 1982; 43: 252-254.
    PubMedGoogle Scholar
  • 25 Grabner A. Enzootische Leberdystrophie und hepatoenzephales Syndrom bei Pferden durch Vergiftung mit Senecio alpinus. Pferdeheilk 1990; 6: 119-124.
    CrossrefPubMedGoogle Scholar
  • 26 Green CR, Christie GS. Malformations in foetal rats induced by the pyrrolizidine alkaloid, heliotrine. Br J Exp Path 1961; 42: 369-378.
    PubMedGoogle Scholar
  • 27 Harris PN, Henderson FG, Chen KK. Hepatic cirrhosis induced in sheep by Senecio longilobus. AMA Arch Pathol 1957; 64: 297-302.
    PubMedGoogle Scholar
  • 28 Hooper PT. Pyrrolizidine alkaloid poisoning. Pathology with particular reference to differences in animal and plant species. In: Effects of Poisonous Plants on Livestock. Keeler RF, Van Kampen KR, James LF. eds. New York: Academic Press; 1978: 161-176.
    Google Scholar
  • 29 http://www.clinitox.chbzw. www.vetpharm.uzh.ch/giftdb/pflanzen/0038_vet.html.
    PubMed
  • 30 http://www.landwirtschaftskammer.de/fachangebot/ackerbau/gruenland/jakobsgreiskraut.htm.
    PubMed
  • 31 http://laves.niedersachsen.de/live/live.php?navigation_id=20045&article_id=73807&_psmand=23.
    PubMed
  • 32 http://www.tierisch.ch/Berichte/Jacobs-Kreuzkraut.html.
    PubMed
  • 33 Huxtable RJ. Human embryotoxicity of pyrrolizidine-containing drugs. Hepatology 1989; 9: 510-511.
    CrossrefPubMedGoogle Scholar
  • 34 IPCS International Program of Chemical Society: Criteria 80. Pyrrolizidine Alkaloids. World Health Organization; 1988
    Google Scholar
  • 35 Jago MV, Bingley JB, Piercy DWT, Whittam JH, Lanigan GW, Titchen DA. Excretion of the pyrrolizidin alkaloid heliotrine in the urine and bile of sheep. J Pathol Bacteriol 1969; 98: 115-128.
    PubMedGoogle Scholar
  • 36 Ji L, Liu T, Chen Y, Wang Z. Protective mechanisms of N-acetyl-cysteine against pyrrolizidine alkaloid clivorine-induced hepatoxicity. J Cell Biochem 2009; 108: 424-432.
    CrossrefPubMedGoogle Scholar
  • 37 Johnson AE. Changes in calves and rats consuming milk from cows fed chronic lethal doses of Senecio jacobaea(tansy ragwort). Am J Vet Res 1976; 37: 107-110.
    PubMedGoogle Scholar
  • 38 Johnson AE. Failure of mineral-vitamin supplement to prevent tansy ragwort (Senecio jacobaea) toxicosis in cattle. Am J Vet Res 1982; 43: 718-723.
    PubMedGoogle Scholar
  • 39 Johnson AE. Toxicity of tansy ragwort to cattle. In: Symposium on pyrrolizidine (senecio) alkaloids: toxicity, metabolism, and poisonous plant control measures. Cheeke PR. ed. 1979: 129-134. Nutrition Research Institute, Oregon State University; Corvallis, OR.:
    Google Scholar
  • 40 Johnson AE, Molyneux RJ, Stuart LD. Toxicity of Riddell’s groundsel (Senecio riddellii) to cattle. Am J Vet Res 1985; 46: 577-582.
    PubMedGoogle Scholar
  • 41 Kempf M. Entwicklung und Anwendung von Methoden zur Erfassung von Pyrrolizidinalkaloiden in Honig und Pollen. Thesis 2009. Universität Würzburg;
    Google Scholar
  • 42 Kempf M, Wittig M, Schoenfeld K, Cramer L, Schreier P, Beuerle T. Pyrrolizidine alkaloids in food; downstream contamination in the food chain caused by honey and pollen. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2011; 28 (03) 325-331.
    CrossrefPubMedGoogle Scholar
  • 43 Kempf M, Heil S, Hasslauer I, Schmidt L, von der Ohe K, Theuring C, Reinhard A, Schreier P, Beuerle T. Pyrrolizidine alkaloids in pollen and pollen products. Mol Nutr Food Res 2010; 54: 292-300.
    CrossrefPubMedGoogle Scholar
  • 44 Kim HY, Stermitz FR, Molyneux RJ, Wilson DW, Taylor D, Coulombe RA. Structural influences on pyrrolizidine alkaloid-induced cytopathology. Toxicol Appl Pharmacol 1993; 122: 61-69.
    CrossrefPubMedGoogle Scholar
  • 45 Knight AP. Plant poisoning of horses. In: Feeding and Care of the Horse. 2nd ed.. Lewis LD. ed. Philadelphia: Lippincott Williams & Wilkins; 1996: 447-501.
    Google Scholar
  • 46 Köhler H. Über ungewöhnlich große Leberzellen beim Leberkoller des Pferdes (Schweinsberger Krankheit). Zbl allg Path Path Anat 1950; 86: 282-288.
    PubMedGoogle Scholar
  • 47 Kovach JS, Ames MM, Powis G, Moertel CG, Hahn RG, Creagan ET. Toxicity and pharmacokinetics of a pyrrolizidine alkaloid, indicine-N-oxide, in humans. Cancer Res 1979; 39: 4540-4544.
    PubMedGoogle Scholar
  • 48 McLean EK. The toxic actions of pyrrolizidine (Senecio) alkaloids. Pharmacol Rev 1970; 22: 429-483.
    PubMedGoogle Scholar
  • 49 Mendel VE, Witt MR, Gitchell BS, Grible DN, Rogers QR, Segall HJ, Knight HD. Pyrrolizidine alkaloid-induced liver disease in horses: An early diagnosis. Am J Vet Res 1988; 49: 572-578.
    PubMedGoogle Scholar
  • 50 Medeiros RMT, Górniak SL, Guerra JL. Fetotoxicity and reproductive effects of monocrotaline in pregnant rats. J Ethnopharmacol 2000; 69: 181-188.
    CrossrefPubMedGoogle Scholar
  • 51 Miranda CL, Chung W, Reed RE, Zhao X, Hendeson MC, Wang JL, Williams DE, Buhler DR. Flavin-containing monooxygenase: a major detoxifying enzyme for the pyrrolizidine alkaloid senecionine in guinea pig tissues. Biochem Biophys Res Commun 1991; 178: 546-552.
    CrossrefPubMedGoogle Scholar
  • 52 Molyneux RJ, James LF. Pyrrolizidine alkaloids in milk: thresholds of intoxication. Vet Hum Toxicol 1990; 32 (Suppl.): 94-103.
    PubMedGoogle Scholar
  • 53 Moore RE, Knottenbelt D, Matthews JB, Beynon RJ, Whitfield PD. Biomarkers for ragwort poisoning in horses: identification of protein targets. BMC Veterinary Res 2008; 4: 30-40.
    PubMedGoogle Scholar
  • 54 Muhammad F, Riviere JE. Dermal toxicity. In: Veterinary Toxicology. Gupta RC. ed. New York: Academic Press Elsevier; 2007: 263-276.
    Google Scholar
  • 55 Newberne PM. The influence of a low lipotrope diet on response of maternal and fetal rats to lasiocarpine. Cancer Res 1968; 28: 2327-2337.
    PubMedGoogle Scholar
  • 56 Pearson EG. Liver failure attributable to pyrrolizidine alkaloid toxicosis and associated with inspiratory dyspnoe in ponies: Three cases (1982–1988). JAVMA 1991; 198: 1651-1654.
    PubMedGoogle Scholar
  • 57 Persaud TV, Hoyte DA. Pregnancy and progeny in rats treated with the pyrrolizidine alkaloid fulvine. Exp Pathol (Jena) 1974; 9: 59-63.
    PubMedGoogle Scholar
  • 58 Peterka M, Sarin S, Roeder E, Wiedenfeld H, Halašková M. Differing embryotoxic effects of senecionine and senecionine-N-oxide on the chick embryo. Funct Dev Morphol 1994; 4: 89-92.
    PubMedGoogle Scholar
  • 59 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.
    CrossrefPubMedGoogle Scholar
  • 60 Petzinger E. Pyrrolizidinalkaloide und die Seneciose bei Tieren. Teil 1: Vorkommen, Chemie, Toxikologie. Tierärztl Prax 2011; 39 (G): 221-230.
    PubMedGoogle Scholar
  • 61 Pierson ML, Cheeke PR, Dickinson EO. Resistance of the rabbit to dietary pyrrolizidine (Senecio) alkaloids. Res Comm Chem Path Pharm 1977; 16: 561-564.
    PubMedGoogle Scholar
  • 62 Pohlenz J, Lüthy J, Minder HP, Bivetti A. Enzootische Leberzirrhose beim Rind, verursacht durch Pyrrolizidinalkaloide nach Aufnahme von Senecio alpinus (Alpenkreuzkraut). Schweiz Arch Tierheilk 1980; 122: 183-193.
    PubMedGoogle Scholar
  • 63 Prakash AS, Perreira TN, Reilly PEB, Seawright AA. Pyrrolizidine alkaloids in human diet. Mut Res 1999; 443: 53-67.
    PubMedGoogle Scholar
  • 64 Rasenack R, Müller C, Kleinschmidt M, Rasenack J, Wiedenfeld H. Venoocclusive disease in a fetus caused by pyrrolizidine alkaloids of food origin. Fetal Diagn Ther 2003; 18: 223-225.
    CrossrefPubMedGoogle Scholar
  • 65 Roeder E. Analysis of pyrrolizidine alkaloids. Curr Org Chem 1999; 3: 557-576.
    PubMedGoogle Scholar
  • 66 Roulet M, Laurini R, Rivier L, Calamé A. Hepatic veno-occlusive disease in newborne infant of a woman drinking herbal tea. J Pediatr 1988; 112: 433-436.
    CrossrefPubMedGoogle Scholar
  • 67 Schoental R. Liver lesions in young rats suckled by mothers treated with the pyrrolizidine (Senecio) alkaloids, Lasiocarpine and retrorsine. J Pathol Bacteriol 1959; 77: 485-495.
    CrossrefPubMedGoogle Scholar
  • 68 Schultz S. Giftpflanze im Rucola. Gestrüpp des Grauens. Spiegel online 12. August 2009 http://www.spiegel.de/wirtschaft/service/0,1518,643634,00.html.
    PubMedGoogle Scholar
  • 69 Seibold-Weiger K, Vochem M, Mackensen-Haen S, Speer C. Fatal hepatic veno-occlusive disease in a newborn infant. Am J Perinat 1997; 14: 107-111.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 70 Sergi C, Beedgen B, Lindenkamp O, Hofmann WJ. Fatal course of venoocclusive disease of the liver (endophlebitis hepatic obliterans) in a preterm infant. Pathol Res Pract 1999; 195: 847-851.
    CrossrefPubMedGoogle Scholar
  • 71 Shull LR, Buckmaster GW, Cheeke PR. Factors influencing pyrrolizidine (Senecio) alkaloid metabolism: species, liver sulfhydryls, and rumen fermentation. J Anim Sci 1976; 43: 1247-1253.
    CrossrefPubMedGoogle Scholar
  • 72 Soto-Blanco B, Medeiros RMT, Guerra JL, Górniak SL. Lack of protective action of cysteine against the fetotoxic effect of monocrotaline. Food Chem Toxicol 2001; 39: 635-639.
    CrossrefPubMedGoogle Scholar
  • 73 Stegelmeier BL, Edgar JA, Steven M, Gardner DR, Schoch TK, Coulumbe RA, Molyneux RJ. Pyrrolizidine alkaloid plants, metabolism and toxicity. J Natural Tox 1999; 8: 95-116.
    PubMedGoogle Scholar
  • 74 Sundareson AE. An experimental study on placental permeability to cirrhotic poisons. J Pathol Bacteriol 1942; 54: 289-298.
    CrossrefPubMedGoogle Scholar
  • 75 Thorpe E, Ford EJH. Development of hepatic lesions in calves fed ragwort (Senecio jacobaea). J Comp Pathol 1968; 78: 195-218.
    CrossrefPubMedGoogle Scholar
  • 76 Tu Z-B, Konno C, Soejarto DD, Waller DP, Bingel AS, Molyneux RJ, Edgar JA, Cordell GA, Fong HHS. Identification of senecionine and senecionine N-oxide as antifertility constituents in Senecio vulgaris . J Pharmaceut Sci 1988; 77: 461-463.
    CrossrefPubMedGoogle Scholar
  • 77 White IN, Mattocks AR, Butler WH. The conversion of the pyrrolizidine alkaloid retrorsine to pyrrolic derivatives in vivo and in vitro and its acute toxicity to various animal species. Chem Biol Interact 1973; 6: 207-218.
    CrossrefPubMedGoogle Scholar
  • 78 White RD, Krumperman PH, Cheeke PR, Deinzer ML, Buhler DR. Mutagenic responses of tansy ragwort (Senecio jacobaea) plant, pyrrolizidine alkaloids and metabolites in goat milk with salmonella/mammalian-microsome mutagenicity test. J Animal Sci 1984; 58: 1245-1254.
    CrossrefPubMedGoogle Scholar
  • 79 WHO (1988) Pyrrolizidine alkaloids. Environmental Health Criteria No. 80, Geneva. International Programme on Safety. 275-337.
    PubMedGoogle Scholar
  • 80 Wiedenfeld H, Roeder E, Bourauel T, Edgar J. eds. Pyrrolizidine Alkaloids. Structure and Toxicity. Bonn: University Press; 2008: 1-143.
    Google Scholar
  • 81 Wiedenfeld H, Edgar J. Toxicity of pyrrolizidine alkaloids to humans and ruminants. Phytochem Rev 2011; 10: 137-151.
    CrossrefPubMedGoogle Scholar
  • 82 Wiedenfeld H. Plants containing pyrrolizidine alkaloids – toxicity and problems. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2011; 28 (03) 282-292.
    CrossrefPubMedGoogle Scholar
  • 83 Yan CC, Huxtable RJ. Relationship between the glutathione concentration and metabolism of the pyrrolizidine alkaloid monocrotaline in isolated perfused liver. Toxicol Appl Pharmacol 1995; 130: 13-17.
    PubMedGoogle Scholar