Pyrrolizidine alkaloids (PA) are found mainly in plants of three families: boraginaceae, Compositae and Leguminosae. In North America, PA poisoning of livestock is caused primarily by consumption of Senecio and Crotalaria spp. The PA of Senecio spp. cause irreversible hepatic damage; toxicity signs are a consequence of impaired liver function. Crotalaria intoxication leads to pulmonary damage as a primary effect; hepatic effects are less prominent. Large species differences exist in susceptibility to PA toxicosis. Small herbivores such as sheep, goats, rabbits, guinea pigs and other herbivorous laboratory animals are highly resistant to PA toxicity, associated with a low rate of hepatic production of reactive metabolites (pyrroles) and(or) a high rate of activity of detoxifying enzymes. Diester PA common to Heliotropium and Echium spp. are metabolized in the ovine rumen to 1-methyl metabolites, whereas the macrocyclic ester PA of Senecio spp. are not. Exposure to PA results in high concentrations of liver Cu, reduced liver Zn, and abnormal Fe metabolism with hematopoiesis markedly impaired. Pyrrolizidine alkaloid toxicity alters vitamin A metabolism in rats, depressing plasma and liver levels of vitamin A. Synthetic antioxidants in the diet confer protective activity in laboratory animals (e.g., rats, mice) against PA toxicoses. The PA and their metabolites are secreted in the milk of lactating animals, but this probably does not represent a significant human health hazard.

Toxicity and metabolism of pyrrolizidine alkaloids

Plants that affect the skin and liver are considered together in this chapter because some plant toxins cause liver disease that results in secondary skin disease. One of the most noticeable signs indicative of an animal with liver disease is the appearance of dermatitis and hair loss affecting the white-skinned areas. Some plants contain compounds or pigments that once absorbed from the digestive system induce a direct effect on nonpigmented skin when it is exposed to light, without any effect on the liver. Other plants contain toxic alkaloids that cause irreversible liver disease resulting in a secondary photosensitization. Yet other plants have compounds that cause a skin reaction when they come in contact with skin, or they have spines or thorns that can cause mechanical injury to the skin.

A Guide to Plant Poisoning of Animals in North America

This study was designed to confirm the toxicity of a plant implicated in an outbreak of poisoning of stock in Frankfort, Free State Province, South Africa. Cows died acutely after being introduced into a camp, where an abundant, green shrublet was noted to be heavily grazed. This plant was subsequently identified as Senecio inaequidens DC. (Asteraceae) by the South African National Biodiversity Institute (SANBI). Extraction and chemical analyses for pyrrolizidine alkaloids (PAs) in Senecio inaequidens revealed the presence of 4 different compounds, namely retrorsine and senecionine (known to be hepatotoxic) and 2 unidentified compounds. The average total PA (free base plus N-oxide) concentration in plant parts of S. inaequidens collected at Frankfort during the outbreak was 0.81 %, compared with the total alkaloid content in the dried, milled S. inaequidens plant material, collected 7 weeks after the outbreak, of only 0.18 %. Male Sprague-Dawley rats (n=4), aged 8-9 weeks, were dosed per os. Each rat received a different dose of the crude Senecio inaequidens extract, ranging from 0.049 mg/g body weight (b.w.) to 0.25 mg/g b.w. No clinical signs were observed in the rat receiving the lowest dose. Rats receiving higher doses showed depression, an unsteady gait, pilo-erection and jaundice, which was particularly noticeable in the ears. Clinical chemistry evaluation revealed an increase in the activities of ALP (except Rat 4), AST and GGT in all animals. Total serum bilirubin, creatinine and urea concentrations were also elevated. All rats had low serum globulin concentrations with an A/G ratio above 1.2. Post mortem examination of the rats revealed marked hepatic lesions. Histopathologically, these changes were characterised by necrosis (variable in extent) of the centrilobular and midzonal hepatocytes (but sparing the portal hepatocytes), with extensive haemorrhage and congestion. Proliferation of the bile ducts, fibrosis and oedema were also present. Ultrastructural changes in affected rats were characterised by margination of chromatin, the presence of numerous autolysosomes in necrotic hepatocytes, intramitochondrial woolly inclusions and changes in the endoplasmic reticulum. A sheep, also dosed with the crude extract, failed to exhibit clinical signs, clinical chemistry aberrations or macroscopic lesions; however, examination of the liver of this sheep revealed histopathological and ultrastructural changes similar, though milder, to those displayed by the rats. Pyrrolizidine alkaloids were extracted from the liver and kidneys of the rats and the sheep. In the case of the sheep, retrorsine was also detected in the lungs, urine and bile.

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The toxicity of Senecio inaequidens DC.

approved: Peter R. Cheeke Three in vivo and 3 in vitro studies were conducted. A seven week study on the effect of feeding ammoniated endophyte-infected tall fescue (E+) straw to steers showed a reduction in digestibility (P<0.05) with no influence (P>.005) on the feed intake (FI) , average daily gain (ADG) or rectal temperature (RT) (P>.05); however, marginally low serum prolactin (PRL) was observed. A study on wethers using E+ seed with dietary levels of the major ergopeptide alkaloid, ergovaline (EV), ranging from 0 to 2000 ppb showed reduced FI, ADG and, serum PRL and was accompanied by increased RT (P<0.05). Feeding of wethers with ammoniated seed screenings, however, did not improve wether performance or serum PRL; this was hypothesized to be because the feed was not ground, thus reducing exposure of alkaloids within the seed to the ammonia. Another study evaluated the interaction of ergot alkaloids (EA) in E+ TF seed and pyrrolizidine alkaloids (PA) in tansy ragwort in influencing liver function in sheep which are resistant to PA toxicity. It was hypothesized that EV-induced low serum PRL would Redacted for privacy increase susceptibility to hepatotoxic PA because PRL has hepatogenic properties. No interaction between the two alkaloids was detected as assessed by gammaglutamyl transferase activity and by bromsulfophthalein clearance tests. This indicates that the target organs of the two types of alkaloids are different. The in vitro studies focused on alkaloid reduction methods through acid or alkali treatment, ammoniation, and ensiling after grinding. Quadratic regression models best predicted the association of the levels of EV in E+ TF seed with pH and mechanical treatment. Ammoniation improved the detoxification rate of E+ TF products and TR and grinding assisted the toxin reduction process. Ensiling tended to reduce the alkaloids in E+ TF and TR but its effects were not consistent; there appeared to be no interaction between ensiling and grinding. The fact that serum PRL of wethers was reduced at dietary intake levels of as low as 50 ppb or 6.5 ug/kg BW75 and production at this EV intake was reduced to 75% of control deserves cautionary measures when feeding E+ TF in Oregon. Reduced performance is due to lowered FI and digestibility; while reduction in serum PRL is due to the effects of EA on dopamine and its receptors which antagonize PRL secretion. ©Copyright by Woldu T. Debessai August 26, 1997 All Rights Reserved Evaluation of Endophyte-Infected Tall Fescue Products, their Interaction with Senecio jacobaea in Ruminants, and Detoxification of Alkaloids by Ammoniation or Ensiling after Grinding

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Evaluation of endophyte-infected tall fescue products, their interaction with Senecio jacobaea in ruminants, and detoxification of alkaloids by ammoniation or ensiling after grinding

Im Vordergrund der Vergiftungen mit Pyrrolizidinalkaloiden (PA) steht die chronische Toxinaufnahme durch Verzehr kontaminierten Heus, die zu Leberschaden in Form einer letal verlaufenden Leberzirrhose bzw. einer venenokklusiven Erkrankung in Leber und Lunge fuhren kann. Die Vergiftungssymptomatik ist nicht bei allen Tierspezies identisch und bezieht auch zentralnervose Storungen mit ein. Bei betroffenen Pferden werden deutlich erhohte Serumwerte hepatogener Enzyme und eine verzogerte Bromsulphthalein-Retentionszeit als Indikatoren fur 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 Korpergewicht um ein Mehrfaches ubersteigen, Giftwirkungen auftreten. Dagegen sind Schweine, Rinder und Pferde sowie Huhner und ebenso der Mensch gegenuber Vergiftungen mit PA-haltigen Pflanzen sehr empfindlich. Bei empfindlichen Tierspezies genugen sehr geringe Mengen an getrocknetem kontaminiertem Heu, um die als unbedenklich fur den Menschen angesehene tagliche PA-Aufnahmemenge von 1 μg/kg KM zu uberschreiten. Damit sind die Futtermittel, in denen erkennbare Pflanzenteile an Jakobskreuzkraut vorkommen, von der Verfutterung auszuschliesen bzw. zu vernichten.

Pyrrolizidinalkaloide und die Seneciose bei Tieren

Dried tansy ragwort containing pyrrolizidine alkaloids was fed as 2.5% of a complete (control) diet to Hereford steers, with and without (basal) a mixture of additives. The additives provided a dietary supplement equivalent to 0.1% ethoxyquin, 1% methionine hydroxy analog, 2% MgO, 2.7 mg of vitamin B6/kg of diet, 50 micrograms of vitamin B12/kg of diet, 0.45 g of folic acid/kg of diet, and 0.2 g of cobalt/kg of diet. The additives did not alter tansy ragwort toxicity substantially, as assessed by liver histologic changes, sulfobromophthalein clearance rate, and serum gamma-glutamyl transpeptidase activity. After 281 days, 1 of 4 steers fed the basal diet was alive, whereas 3 of 4 steers in the basal plus additives group were alive, suggesting some protective activity. The chronic lethal dose of tansy ragwort in steers was 3.6% of initial body weight.

Effects of dietary supplementation with ethoxyquin, magnesium oxide, methionine hydroxy analog, and B vitamins on tansy ragwort (Senecio jacobaea) toxicosis in beef cattle.

Lassen Ed

Papers

Effects of dietary supplementation with ethoxyquin, magnesium oxide, methionine hydroxy analog, and B vitamins on tansy ragwort (Senecio jacobaea) toxicosis in beef cattle.