Current ideas on the pathophysiology and treatment of lantana poisoning of ruminants

Lantana poisoning in ruminants results from the ingestion of toxic varieties of the plant Lantana camara, which contain the triterpene acids lantadene A and lantadene B. Poisoning results in intrahepatic cholestasis and the consequences of the liver injury include jaundice, photosensitisation and ruminal stasis. The decreased ruminal motility causes toxic material to be retained in the rumen and continuous absorption of toxins from the rumen maintains the disease. Lantana poisoning can best be treated by preventing further absorption of toxins. This can be achieved by giving a large quantity of activated charcoal into the rumen together with a large volume of a multiple electrolyte solution to stimulate ruminal motility and rehydrate the animal. Treatment for photosensitive dermatitis should also be given.     

Vaccination as a possible means of preventing lantana poisoning

The toxic triterpene acids lantadene A and lantadene B were isolated from Lantana camara and conjugated to bovine serum albumen or haemocyanin. The conjugates were emulsified with complete Freund's adjuvant and injected into sheep and cattle. Vaccinated animals produced antibodies against the toxic compounds. Cholestasis was less severe in vaccinated than in non-vaccinated sheep challenged with a toxic dose of lantana. The results indicated a mild protective effect of vaccination against the hepatotoxic effects of lantana toxins.     

Effect of Phenobarbitone Treatment Against Signal Grass (Brachiaria decumbens) Toxicity in Sheep

The effect of phenobarbitone against signal grass (Brachiaria decumbens) toxicity was studied in 26 male crossbred sheep. Grazing on signal grass significantly decreased the concentration of cytochrome P-450 and the activity of drug metabolizing enzymes, viz. aminopyrine-N-demethylase, aniline-4-hydroxylase, UDP- glucuronyltransferase and glutathione-S-transferase in liver and kidneys of affected sheep.Oral administration of phenobarbitone (30 mg/kg body weight) for five consecutive days before grazing on B. decumbens pasture, and thereafter, for three consecutive days every two weeks, resulted in significant increases in hepatic and renal activities of drug-metabolizing enzymes. The induction of drug metabolizing activity in sheep grazing on signal grass group was found to be lower than in animals given phenobarbitone alone. Induction by phenobarbitone provided a degree of protection against the toxic effects of B. decumbens as indicated by the delay in the appearance of signs of toxicity. Furthermore, these were much milder compared to those in the sheep not treated with phenobarbitone. The present study suggests that phenobarbitone-type cytochrome P-450 isoenzyme-induction may increase resistance against signal grass (B. decumbens) toxicity in sheep.     

Investigations into the toxicity of Echium plantagineum in sheep: 2. Pen feeding experiments

In a pen feeding trial fresh Echium plantagineum was fed as the sole diet to crossbred sheep with or without a history of previous access to the plant. Control groups received a diet of lucerne chaff and oats. During the trial, sheep on the Echium diet lost weight and deaths occurred with histological evidence of excessive copper accumulation, usually accompanied by pyrrolizidine alkaloid damage, in the liver and biochemical evidence of liver toxicity. It is concluded that E. plantagineum alone is not a suitable fodder for sheep and can be toxic due to its pyrrolizidine alkaloid content and high copper to molybdenum ratio.     

Bur buttercup poisoning of sheep

Bur buttercup (Ceratocephalus testiculatus) has not been considered to be poisonous, but the sudden death loss of 150 ewes while grazing it prompted study of the plant. It was found that bur buttercup can be highly toxic to sheep, with a lethal dose being as little as 500 g of green plant for a 45-kg sheep. Clinical signs of bur buttercup poisoning are weakness, depression, diarrhea, labored breathing, anorexia, and occasional fever. Postmortem findings include inflammation and edema of the rumen; hemorrhage in the left ventricle of the heart; congestion of the lungs, liver, and kidneys; and excessive fluid in the thoracic and abdominal cavities.     

Cycad (zamia) poisoning in Australia

The Cycads belong to an ancient family of plants and were the cause of the first well documented plant poisoning in Australia when Captain Cook's men and their pigs were affected by eating them. Subsequent reports particularly by early explorers refer to toxicity of the seeds to man. One reason for this was the evidence that the natives ate them. Subsequent reports and experimental work established the toxicity to sheep and cattle. In sheep and cattle 2 syndromes occur, ataxia and liver damage. In cattle the former is the better known, the spinal cord lesion being mainly a demyelination of the sensory pathways. The liver damage is necrosis and fibrosis.     

我国有毒蜜源植物及毒性

环境或气候变化引起蜜蜂采集有毒蜜源植物的花蜜或蜜露,导致生产出含有植物源毒素的有毒蜂蜜,食用此类有毒蜂蜜容易引发中毒。尽管国内外食用蜂蜜中毒的具体原因存在差异,但多数食用蜂蜜中毒事件与有毒蜜源植物之间存在着较大的关联性。我国地域广阔,蜜源植物种类多样,梳理清楚有毒蜜源植物资源及其毒性对蜂蜜安全生产、毒性成分溯源等工作具有极其重要的意义。在广泛文献调研的基础上,对我国分布的15科29种有毒蜜源植物种类、分布区域及花期等进行总结,并结合文献报道的急性毒性试验结果对有毒蜜源植物毒性进行归纳,以期为蜜蜂放养场地选择、蜂蜜安全生产及中毒原因追溯提供科学参考。     

The toxicity of phomopsin for sheep

Pure phomopsin was administered to young Merino x Border Leicester wethers by single subcutaneous (SC) and by single and multiple intraruminal (IR) injection. The toxicity after IR injection was influenced by the size of individual doses and the time over which the total dose was given. At high levels of ingestion the toxicity of phomopsin may be limited by absorption rates; with low daily doses the capacity to repair liver damage may be sufficient to prevent cumulative effects. By SC injection a single dose of 10 micrograms/kg approximated the LD50. By IR injection the overall clinical, biochemical and histological responses closest to these of this SC dose resulted from a single dose of 1,000 micrograms/kg. The same total dose administered at daily rates of 50 or 200 micrograms/kg was more toxic and killed all sheep. A single dose of 500 micrograms/kg caused significant liver damage, but no deaths. Single doses of 125 and 250 micrograms/kg and repeated daily doses of 12.5 micrograms/kg over 16 weeks caused no detectable tissue damage. Inappetence was the most sensitive indicator of phomopsin toxicity. About 10% of the sheep differed substantially from the rest of the flock in their susceptibility to phomopsin poisoning.     

Superphosphate poisoning of sheep: the role of fluoride

Earlier work confirmed that the fundamental lesion of superphosphate poisoning is an acute toxic tubular nephritis in which both phosphate and fluoride may play a part but their respective roles could not be determined. In this study, sheep poisoned by sodium fluoride (NaF) were compared with sheep poisoned by superphosphate containing approximately 1.5% fluoride. The LD₅₀ of NaF was in the range 100 to 300 mg/kg (45 to 135 mg F/kg). This range is of the same order as the amount of fluoride in a toxic dose of superphosphate (70 to 90mg F/kg).

A lethal dose of NaF caused severe depression, salivation, hyperpnoea, blindness, ataxia and incoordination. Death ensued three to 52 hours after dosing. Acute necrotizing rumino-reticulitis and abomasitis and necrosis of epithelial cells in the proximal convoluted tubules of the kidney were the characteristic lesions of NaF toxicity.

Superphosphate poisoning took a more protracted course with depression and diarrhoea as the predominant clinical signs until the terminal coma. As with NaF, the notable lesions were in the gastrointestinal tract and kidneys, but were less severe.

Although there were differences in the clinical and pathological manifestations of the two forms of poisoning, the comparable toxic dose of NaF and of the fluoride in a toxic dose of superphosphate, and the similar target organs involved, support the view that fluoride plays a dominant role in the pathogenesis of superphosphate poisoning. It is probable that phosphate plays a contributory role but the nature of the interaction of fluoride and phosphate remains to be established.     

Experimental Photosensitization and Toxicity in Sheep Produced by Tetradymia glabrata

Factors affecting the phototoxic response of sheep to Tetradymia glabrata were investigated. Photosensitization, which occurs regularly in the field situation, was unpredictable and difficult to produce experimentally. In attempting to understand this unpredictability we concluded that the plant does not lose its toxicity after field collection either through volatility of the toxin, plant enzymatic degradation of the toxin or dehydration. The chlorophyll source, from which the suspected phototoxic agent phylloerythrin is derived, did not appear to be important. The single case of photosensitization produced gave no clues as to why it occurred. Some predisposing factors important to the production of tetradymia related photosensitization in sheep are unknown.

In disagreement with previous reports the hepatotoxic response of sheep to Tetradymia glabrata was extremely variable. Also plants in comparable stages of growth, but from different locations, varied in their toxicity to sheep. Young budding plants are most toxic, however, toxicity of the plant remains through maturity.

     

The toxicity of myoporum tetrandrum (Boobialla) and myoporaceous furanoid essential oils for ruminants

Boobialla (Myoporum tetrandrum)leaf contains from 0.25 to 0.5% wet weight of furanoid sesquiterpene essential oils of which the main component is dehydrongaione. The plant was toxic when dosed to calves at equivalent dose rates of oils of from 50 to 134 mg/kg, causing mainly extensive haemorrhagic centrillobular necrosis; and to sheep at equivalent dose rates of oil of from 55 to 66 mg/kg, causing either centrilobular or periportal liver lesions with or without acute pulmonary oedema. An essential oil mixture of similar composition derived from Myoporum deserti produced similar syndromes. In addition, treatment of calves with phenobarbitone or Melaleuca linariifolia essential oils prior to dosing with the Myoporum oils caused periportal hepatic necrosis rather than the centrilobular lesion which occurred usually in this species. The liver lesions found in the experimental calves and sheep respectively, were thus similar to those reported in suspected field cases of Boobialla poisoning in cattle and goats in Western Australia. The liver injury that may be expected in intoxication of livestock by myoporaceous plants containing this type of essential oils can thus be either periportal, midzonal or centrilobular necrosis, depending, probably, on the nutritional regime of the animal immediately prior to consumption of the toxic plant.     

Krimpsiekte and acute cardiac glycoside poisoning in sheep caused by bufadienolides from the plant Kalanchoe lanceolata Forsk

Three toxic bufadienolides , one characterized as hellibrigenin 3-acetate, have been isolated from Kalanchoe lanceolata Forsk. Typical signs of cardiac glycoside poisoning, involving the gastro-intestinal, neuromuscular and cardiovascular systems, could be induced by drenching the milled plant to sheep. Such signs could also be induced by dosing the bufadienolides to sheep or by injecting them into both guinea-pigs (subcutaneously) and sheep (intravenously). The specific paretic syndrome, krimpsiekte , on the other hand, was reproduced only by the repeated intravenous administration of smaller doses of the 2 unknown bufadienolides to sheep. Histopathological examination revealed a mild to severe multifocal cardiomyopathy in sheep receiving plant material or bufadienolides .     

Effect of phenobarbitone treatment against signal grass (Brachiaria decumbens) toxicity in sheep

The effect of phenobarbitone against signal grass (Brachiaria decumbens) toxicity was studied in 26 male crossbred sheep. Grazing on signal grass significantly decreased the concentration of cytochrome P-450 and the activity of drug metabolizing enzymes, viz. aminopyrine-N-demethylase, aniline-4-hydroxylase, UDP- glucuronyltransferase and glutathione-S-transferase in liver and kidneys of affected sheep.Oral administration of phenobarbitone (30 mg/kg body weight) for five consecutive days before grazing on B. decumbens pasture, and thereafter, for three consecutive days every two weeks, resulted in significant increases in hepatic and renal activities of drug-metabolizing enzymes. The induction of drug metabolizing activity in sheep grazing on signal grass group was found to be lower than in animals given phenobarbitone alone. Induction by phenobarbitone provided a degree of protection against the toxic effects of B. decumbens as indicated by the delay in the appearance of signs of toxicity. Furthermore, these were much milder compared to those in the sheep not treated with phenobarbitone. The present study suggests that phenobarbitone-type cytochrome P-450 isoenzyme-induction may increase resistance against signal grass (B. decumbens) toxicity in sheep.     

Superphosphate poisoning of sheep: the role of fluoride

Earlier work confirmed that the fundamental lesion of superphosphate poisoning is an acute toxic tubular nephritis in which both phosphate and fluoride may play a part but their respective roles could not be determined. In this study, sheep poisoned by sodium fluoride (NaF) were compared with sheep poisoned by superphosphate containing approximately 1.5% fluoride. The LD50 of NaF was in the range 100 to 300 mg/kg (45 to 135 mg F/kg). This range is of the same order as the amount of fluoride in a toxic dose of superphosphate (70 to 90 mg F/kg). A lethal dose of NaF caused severe depression, salivation, hyperpnoea, blindness, ataxia and incoordination. Death ensued three to 52 hours after dosing. Acute necrotizing rumino-reticulitis and abomasitis and necrosis of epithelial cells in the proximal convoluted tubules of the kidney were the characteristic lesions of NaF toxicity. Superphosphate poisoning took a more protracted course with depression and diarrhoea as the predominant clinical signs until the terminal coma. As with NaF, the notable lesions were in the gastrointestinal tract and kidneys, but were less severe. Although there were differences in the clinical and pathological manifestations of the two forms of poisoning, the comparable toxic dose of NaF and of the fluoride in a toxic dose of superphosphate, and the similar target organs involved, support the view that fluoride plays a dominant role in the pathogenesis of superphosphate poisoning. It is probable that phosphate plays a contributory role but the nature of the interaction of fluoride and phosphate remains to be established.     

Suspected Vestia foetida poisoning in young goats

CASE HISTORY: Two crossbred, castrated male goats, a 5-month-old and an 8-month-old, were observed ingesting Vestia foetida (Solanaceae). Later, the goats were seen standing splay-legged and apparently disoriented.

CLINICAL FINDINGS: When examined, both goats were in sternal recumbency and had mydriasis; the younger goat had a diminished menace response. When the goats were made to stand, they were ataxic and had muscle fasciculations of the hindquarters and face. Both had halitosis consistent with the odour of crushed Vestia leaves. The animals were treated with a mixture of vitamins and intravenous diazepam. The older goat recovered but the younger goat died and was necropsied. This animal had severe periacinar necrosis and fatty change in the liver, as well as fatty nephrosis.

DIAGNOSIS: Probable Vestia foetida poisoning.

CLINICAL RELEVANCE: The introduction of Vestia foetida to New Zealand and the apparent palatability of the plant necessitate that veterinarians and owners be knowledgeable about its potential toxicity. Differential diagnoses for the liver lesions (in New Zealand) would include Cestrum poisoning, acute seneciosis, acute blue-green algal poisoning, and acute and chronic copper poisoning.     

Cardiac glycoside poisoning in sheep caused by Urginea physodes (Jacq.) Bak. and the isolated physodine A

Urginea physodes (Jacq.) Bak., a species closely related to or possibly synonymous with U. pusilla, is described and its distribution given. Four bufadienolides were isolated from U. physodes and the approximated LD50 and cumulative effect of some of them determined in guinea pigs. The most toxic one proved to be mildly cumulative. Typical signs of acute cardiac glycoside poisoning, involving the locomotory, gastro-intestinal, respiratory and cardiac system, were seen in the field cases and/or were experimentally induced by the plant. Similar signs could also be induced by injecting the isolated bufadienolide, physodine A, to a sheep.     

Protective effects of antioxidants on bitterweed (Hymenoxys odorata DC) toxicity in sheep

Antidotal effects of the 2 antioxidants butylated hydroxyanisole (BHA) and ethoxyquin (EQ) were evaluated in bitterweed (Hymenoxys odorata DC) toxicosis in sheep. Bitteerweed contains a toxic sesquiterpene lactone, hymenoxon, the toxicity of which is reduced by cysteine. Both BHA and EQ are known to induce hepatic glutathione production in rodents. Treatment of sheep with EQ (2.5 g/sheep/day for 9 days before poisoning) gave significant protection from toxic doses of bitterweed, but the protective effect of BHA was insignificant. Of 6 sheep given EQ in the feed, 5 survived 7 doses of bitterweed (4 g/kg/day or higher for 7 days), whereas 5 of 7 controls and 4 of 7 sheep given feed with added BHA died. The added EQ in the feed decreased the serum alkaline phosphatase activity and total protein, albumin, and calcium concentrations. Seemingly, EQ is the first protective agent with field application potential for bitterweed toxicity.     

《马可波罗游记》中记载的肃州毒草及其生态环境背景调查

调查了<马可波罗游记>所记载的中国古代肃州引起牲畜中毒的毒草类型、分布特征及其发育地的生态环境背景.结果表明:在马可波罗当年旅行经过的肃州地区,狼毒Stellera chamaejasme,棘豆Oxytropis,醉马草Achnatherum inebrians 3种毒草大面积分布,已泛滥成灾,造成了数万头(只)牛、羊等家畜大量中毒死亡,严重影响了当地畜牧业的发展.肃南县是毒草生态灾害的重灾区,狼毒、棘豆、醉马草在该区广泛发育.狼毒、醉马草、黄花棘豆O.ochranthd发育在海拔3000 m左右、降水量近300 mm的祁连山中高山区草原生态环境;小花棘豆O.glabra分布在降水量不到100mm、蒸发量可达2 900 mm、严重盐碱化的明花区走廊荒漠草原生态环境.棘豆植物分布区地理位置和牲畜中毒征状说明肃南县的棘豆毒草很可能是<马可波罗游记>中所记栽的引起牲畜中毒的毒草.     

Blindness and encephalopathy caused by Helichrysum argyrosphaerum DC. (Compositae) in sheep and cattle.

An outbreak of amaurosis and paresis was observed amongst sheep, and occasionally cattle, which had been grazing on pastures consisting mainly of Helichrysum argyrosphaerum DC. A similar syndrome was produced by feeding the suspect plant to sheep, thereby providing proof if its toxicity. Although none of the sheep became blind and only one developed paralysis, typical sponly lesions were detected in the brains and optic fasciculi of all the experimental animals. The lesion had specific predilection sites, such as the white matter around the lateral ventricles, the optic tracts plus chiasm, the pyramidal tracts and the brachium pontis. Enlargement of the optic fasciculi furthermore gave rise to malacia, papilloedema and retinal changes. Some aged sheep developed cataracts approximately 2-3 months after the initial outbreaks of amaurosis had occurred. Circumstantial and histopathological evidence suggests that the cataracts may be due to chronic Helichrysum poisoning, but this could not confirmed in the present investigation.     

Investigations into the toxicity of Echium plantagineum in sheep: 1. Field grazing experiments

A field grazing trial was undertaken to monitor the health and production of crossbred sheep grazing pasture where Echium plantagineum constituted a considerable proportion of the available forage. The trial, conducted for 19 months over successive grazing seasons, demonstrated a significant difference in production, with sheep on the E. plantagineum pasture being lighter and growing less wool compared with sheep on Echium-free pasture. No mortalities involving pyrrolizidine alkaloid poisoning were recorded in sheep grazing E. plantagineum, although there was histological evidence of moderately severe liver damage associated with high liver copper concentrations in at least one sheep following the grazing of large quantities of the plant.