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Tierarztl Prax Ausg G Grosstiere Nutztiere 2011; 39(06): 363-372
DOI: 10.1055/s-0038-1623090
DOI: 10.1055/s-0038-1623090
Übersichtsartikel
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 valuesFurther Information
Publication History
Eingegangen:
15 March 2011
Akzeptiert nach Revision:
17 June 2011
Publication Date:
10 January 2018 (online)
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.
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Literatur
- 1 ANZFA (Australia New Zealand Food Authority (2001) Pyrrolizidine alkaloids in food. A toxicological review and risk assessment. http://www.anzfa.gov.au.
- 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.
- 3 BGA (Bundesgesundheitsamt): Abwehr von Arzneimittelrisiken. Stufe II. Pyrrolizidinhaltige Humanarzneimittel. 10.08.1988; Az: GV 7–7251–01– 25365.
- 4 BGA (Bundesgesundsheitsamt): Abwehr von Arzneimittelrisiken. Stufe II; Bundesanzeiger. 17.06.1992 111: 4805.
- 5 Brink NG. Somatic and teratogenic effects induced by heliotrine in drosophila. Mut Res 1982; 104: 105-111.
- 6 Buckmaster GW, Cheeke PR, Shull LR. Pyrrolidine alkaloid poisoning in rats: protective effects of dietary cysteine. J Anim Sci 1976; 43: 464-473.
- 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.
- 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.
- 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.
- 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.
- 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.
- 12 Cheeke PR. Toxicity and metabolism of pyrrolizidine alkaloids. J Anim Sci 1988; 66: 2343-2350.
- 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.
- 14 Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. COT statement on pyrrolizidine alkaloids in food. Food Standard Agency; 2008
- 15 Crews C, Berthiller F, Krska R. Update on analytical methods for toxic pyrroli zidine alkaloids. Anal Bioanal Chem 2010; 396: 327-338.
- 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.
- 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.
- 18 Dunlop RH, Malbert C-H. eds. Part 2: Pathophysiology of plant toxicants. In: Veterinary Pathophysiology. Ames, Iowa: Blackwell; 2004: 490-499.
- 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.
- 20 Fowler ME. Pyrrolizidine alkaloid poisoning in calves. J Am Vet Med Assoc 1968; 152: 1131-1137.
- 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.
- 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.
- 23 Giles CJ. Outbreak of ragwort (Senecio jacobaea) poisoning in horses. Equine Vet J 1983; 15: 248-250.
- 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.
- 25 Grabner A. Enzootische Leberdystrophie und hepatoenzephales Syndrom bei Pferden durch Vergiftung mit Senecio alpinus. Pferdeheilk 1990; 6: 119-124.
- 26 Green CR, Christie GS. Malformations in foetal rats induced by the pyrrolizidine alkaloid, heliotrine. Br J Exp Path 1961; 42: 369-378.
- 27 Harris PN, Henderson FG, Chen KK. Hepatic cirrhosis induced in sheep by Senecio longilobus. AMA Arch Pathol 1957; 64: 297-302.
- 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.
- 29 http://www.clinitox.chbzw. www.vetpharm.uzh.ch/giftdb/pflanzen/0038_vet.html.
- 30 http://www.landwirtschaftskammer.de/fachangebot/ackerbau/gruenland/jakobsgreiskraut.htm.
- 31 http://laves.niedersachsen.de/live/live.php?navigation_id=20045&article_id=73807&_psmand=23.
- 32 http://www.tierisch.ch/Berichte/Jacobs-Kreuzkraut.html.
- 33 Huxtable RJ. Human embryotoxicity of pyrrolizidine-containing drugs. Hepatology 1989; 9: 510-511.
- 34 IPCS International Program of Chemical Society: Criteria 80. Pyrrolizidine Alkaloids. World Health Organization; 1988
- 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.
- 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.
- 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.
- 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.
- 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.:
- 40 Johnson AE, Molyneux RJ, Stuart LD. Toxicity of Riddell’s groundsel (Senecio riddellii) to cattle. Am J Vet Res 1985; 46: 577-582.
- 41 Kempf M. Entwicklung und Anwendung von Methoden zur Erfassung von Pyrrolizidinalkaloiden in Honig und Pollen. Thesis 2009. Universität Würzburg;
- 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.
- 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.
- 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.
- 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.
- 46 Köhler H. Über ungewöhnlich große Leberzellen beim Leberkoller des Pferdes (Schweinsberger Krankheit). Zbl allg Path Path Anat 1950; 86: 282-288.
- 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.
- 48 McLean EK. The toxic actions of pyrrolizidine (Senecio) alkaloids. Pharmacol Rev 1970; 22: 429-483.
- 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.
- 50 Medeiros RMT, Górniak SL, Guerra JL. Fetotoxicity and reproductive effects of monocrotaline in pregnant rats. J Ethnopharmacol 2000; 69: 181-188.
- 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.
- 52 Molyneux RJ, James LF. Pyrrolizidine alkaloids in milk: thresholds of intoxication. Vet Hum Toxicol 1990; 32 (Suppl.): 94-103.
- 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.
- 54 Muhammad F, Riviere JE. Dermal toxicity. In: Veterinary Toxicology. Gupta RC. ed. New York: Academic Press Elsevier; 2007: 263-276.
- 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.
- 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.
- 57 Persaud TV, Hoyte DA. Pregnancy and progeny in rats treated with the pyrrolizidine alkaloid fulvine. Exp Pathol (Jena) 1974; 9: 59-63.
- 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.
- 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.
- 60 Petzinger E. Pyrrolizidinalkaloide und die Seneciose bei Tieren. Teil 1: Vorkommen, Chemie, Toxikologie. Tierärztl Prax 2011; 39 (G): 221-230.
- 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.
- 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.
- 63 Prakash AS, Perreira TN, Reilly PEB, Seawright AA. Pyrrolizidine alkaloids in human diet. Mut Res 1999; 443: 53-67.
- 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.
- 65 Roeder E. Analysis of pyrrolizidine alkaloids. Curr Org Chem 1999; 3: 557-576.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 74 Sundareson AE. An experimental study on placental permeability to cirrhotic poisons. J Pathol Bacteriol 1942; 54: 289-298.
- 75 Thorpe E, Ford EJH. Development of hepatic lesions in calves fed ragwort (Senecio jacobaea). J Comp Pathol 1968; 78: 195-218.
- 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.
- 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.
- 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.
- 79 WHO (1988) Pyrrolizidine alkaloids. Environmental Health Criteria No. 80, Geneva. International Programme on Safety. 275-337.
- 80 Wiedenfeld H, Roeder E, Bourauel T, Edgar J. eds. Pyrrolizidine Alkaloids. Structure and Toxicity. Bonn: University Press; 2008: 1-143.
- 81 Wiedenfeld H, Edgar J. Toxicity of pyrrolizidine alkaloids to humans and ruminants. Phytochem Rev 2011; 10: 137-151.
- 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.
- 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.