Changes in plasma bile acids,plasma amino acids,and hepatic enzyme pools as indices of functional impairment in liver-damaged sheep

Plasma bile acids, plasma amino acids, and the total hepatic pools of aspartate aminotransferase, gamma glutamyltransferase, glutamate dehydrogenase, and sorbitol dehydrogenase were compared in control sheep (Group 1), sheep with subclinical pyrrolizidine alkaloid toxicosis (Group 2), and in sheep with acute hepatocellular necrosis associated with the hemolytic phase of chronic copper poisoning (Group 3). Subclinical pyrrolizidine alkaloid toxicosis was not associated with any changes in bile acid or amino acid status but was associated with a significant decline in the hepatic pools of sorbitol dehydrogenase and aspartate aminotransferase. This observation could not be explained in terms of enzyme leakage from damaged hepatocytes and suggested that pyrrolizidine alkaloids might specifically inhibit hepatocellular enzyme synthesis. Group 3 sheep also had reduced hepatic enzyme pools which were at least partly referable to enzyme leakage from damaged hepatocytes. In these sheep, increases in plasma bile acids were a more sensitive index of hepatic function than were either increased aromatic amino acid concentration or the ratio between branched chain and aromatic amino acids.     

Neurotoxicity in calves induced by the plant, Nierembergia hippomanica Miers var. violacea Millán in South Africa

The plant Nierembergia hippomanica var. violacea has been incriminated in field outbreaks of neurotoxicity in calves in the Free State Province. Hepatotoxicity and electrocardiogram (ECG) deviations were induced in a sheep dosed with 5 g/kg dried plant material on four consecutive days. A calf dosed with 2.5 g/kg dried plant material, on two consecutive days, did not show overt clinical changes. Voluntary ingestion of approximately 30 g/kg fresh flowering plants by a second calf resulted in nervous signs characterized by chewing motions, protrusion of the tongue, dysphagia, hypermetria, ataxia, paresis and lateral recumbency. Salivation, dehydration and cardiac irregularities completed the clinical picture. Clinical chemistry changes revealed muscle damage and increased serum urea and creatinine concentrations indicative of kidney involvement. This is the first confirmed outbreak of Nierembergia hippomanica var. violacea intoxication of stock in South Africa.     

Toxicity of pyrrolizidine alkaloids from Riddell groundsel (Senecio riddellii) to cattle

The toxicity of Riddell groundsel (Senecio riddellii) gavaged to calves at a known lethal rate was compared with the toxicity of riddelliine and riddelliine N-oxide, the pyrrolizidine alkaloids isolated from the plant, which were fed by intraruminal infusion. Doses of the alkaloids were adjusted to the amount determined to be in the plant and fed individually and in combination. The relative toxicosis in the calves was measured by clinical signs, serum enzyme changes, survival time to morbidity, and histologic changes. Calves fed Senecio riddellii by gavage for 20 consecutive days to provide 45 mg of total pyrrolizidine alkaloids/kg of body weight/d developed clinical signs and serum enzyme changes typical of seneciosis, with 100% morbidity. However, calves receiving riddelliine at 4.5 mg/kg/d for 20 days had neither serum enzyme changes nor clinical signs of pyrrolizidine alkaloidosis. Calves treated with riddelliine N-oxide (40.5 mg/kg/d), and with riddelliine (4.5 mg/kg/d) and riddelliine N-oxide (40.5 mg/kg/d) in combination, had 100% morbidity, although the latter group had fewer liver lesions. These results establish that the N-oxide form of the alkaloid alone is capable of inducing typical Senecio toxicosis in cattle and that the free base level of the plant cannot be considered to be the sole factor in assessing the toxicity of S riddellii.     

Mycotoxic tremorgens of Claviceps paspali and Penicillium cyclopium: a comparative study of effects on sheep and cattle in relation to natural staggers syndromes

Claviceps paspali sclerotia were dosed orally at various levels to sheep and cattle and the neurotoxic effects are described. Evidence is presented which indicates that the tremors are produced by a neutral tremorgen fraction. The ergot alkaloids, principally D-lysergic acid alpha-hydroxyethylamide and its isolysergic acid isomer, are not involved. The mixture of C paspali tremorgens has not been separated and characterised but its components are chemically related to other known tremorgens, such as penitrem A, produced by saprophytic moulds, notably Penicillium cyclopium. P cyclopium mycelium and C paspali sclerotia were dosed to produce comparable effects in sheep and in cattle. Similarly, effects of penitrem A and tremorgen concentrate of C paspali were compared after intravenous dosage to sheep. Observed enurotoxic effects of both moulds were identical in most respects. A low level of tremorgenic activity was detected at the honeydew stage of C paspali. These findings are discussed in relation to staggers syndromes occurring in grazing livestock.     

Pyrrolizidine alkaloids and seneciosis in farm animals. part 1: occurrence, chemistry and toxicology

Pyrrolizidine alkaloids belong to a class of phytotoxins which are present in more than 6000 plant species. The disease seneciosis in farm animals represents the severe poisoning by pyrrolizidine alkaloids from plants of the genus Senecio. This form of poisoning has been known since the end of the 19th century in Germany, the USA, Canada and New Zealand, and is mainly caused by Senecio jacobaea and related Senecio spp. in farm animals, including poultry. Animal poisoning by pyrrolizidine alkaloids is of worldwide importance. In Germany poisoning of horses and cattle by Senecio jacobaea, which was earlier named Schweinsberg disease, is of renewed relevance for veterinary medicine. The disease occurs almost entirely as a consequence of chronic poisoning and in general ends fatally. The ultimate cause is the formation of toxic metabolites of pyrrolizidine alkaloids in the liver, and their covalent binding to nucleic acids and proteins leading to liver cirrhosis. Because many pyrrolizidine alkaloids possess mutagenic, and a few also carcinogenic properties, European and international authorities are concerned about possible residue levels in food of animal origin. The review addresses in its first part several aspects, being the occurrence, the chemistry, and the toxicology of pyrrolizidine alkaloids as well as animal intoxications by poisonous plants. In the second part (46) clinical characteristics of animal seneciosis, the therapeutic interventions, the significant species differences and a critical assessment of so-called nontoxic amounts of Senecio plants in animal fodder with reference to cumulative lethal toxin doses are presented.     

Ovine Metabolism of Saponins: Evaluation of a Method for Estimating the Ovine Uptake of Steroidal Saponins from Narthecium ossifragum

A sheep was dosed three times per day over six consecutive days with 70 g Narthecium ossifragum, and once on the seventh day with 70 g N. ossifragum. Additionally, it was dosed once on days 1–7 with 20 mg of [20,23,23-²H₃]sarsasapogenin. After 7 days, the sheep was killed and GC-MS analysis of the free and conjugated sapogenin content in bile, urine, rumen, duodenum, jejunum, colon and rectum samples collected from the sheep, faecal samples collected on days 4–7, and dosed plant material was performed. The N. ossifragum contained mainly sarsasapogenin and smilagenin. Only negligible levels of deuterium-labelled sarsasapogenins were detected in the samples from the animal. Ingested saponins were quickly hydrolysed in the rumen to free sapogenins and, in part, epimerized at C-3 to afford episapogenins. The absorption of free sapogenins appeared to occur in the jejunum. The concentration of sapogenins in faeces reached a plateau 108 h after dosing started.     

Distribution of 5'-nucleotidase in the tissues of sheep and the effect of kidney and liver lesions on the activity of the enzyme in plasma and urine

The distribution of 5'-nucleotidase (5'-NT) activity in the tissues of the sheep differs from that of gamma glutamyl transferase (GGT). Nevertheless, both enzymes are released into the plasma of sheep which have been infected with Fasciola hepatica or in which the bile duct has been ligated. In a sheep dosed with sporidesmin, a fungal toxin which damages the biliary tract, there was an increase in GGT activity in the plasma and urine but no change in 5'-NT activity. Neither enzyme was released into the plasma or urine of sheep dosed with carbon tetrachloride. In sheep with renal tubular necrosis and hepatocellular necrosis caused by dosage with hexachlorobutadiene, both enzymes were released into the plasma, and GGT, but not 5'-NT activity was found in urine. In sheep with tubular necrosis of the kidney caused by the administration of mercuric chloride, GGT activity, but not 5'-NT, increased in the plasma and urine.     

Photosensitisation and crystal-associated cholangiohepatopathy in sheep grazing Brachiaria decumbens

Two outbreaks of photosensitivity and jaundice in sheep grazing the grass, Brachiaria decumbens. In West Java in 1983 and 1983 and 1990 are described. Aggregates of acicular clefts and crystals were present in bile canaliculi, bile ducts, Kupffer cells, hepatocytes and in kidney tubules. The number of crystals increased with the length of exposure to the plant and sheep that died had the largest accumulations. These crystalline structures have been reported before in this syndrome, but are similar to those seen in Tribulus terrestris and Panicum spp toxicities.     

The effect of body condition on serum concentrations of two teratogenic alkaloids (anagyrine and ammodendrine) from lupines (Lupinus species) that cause crooked calf disease

Several species of lupine (Lupinus spp.) are toxic to livestock, causing death losses in sheep and cattle but more commonly crooked calf disease in pregnant range cows. The major toxic alkaloids in lupine are of the quinolizidine alkaloid group and include the teratogen anagyrine, which is primarily responsible for crooked calf disease. Lupines also contain teratogenic piperidine alkaloids including ammodendrine. Previous work in sheep has shown that lupine alkaloid clearance may be influenced by the animal's physiological status. Therefore, the purpose of this study was to determine if differences in body condition of cattle would alter the absorption and elimination of anagyrine or ammodendrine given in a single oral dose as Lupinus leucophyllus or Lupinus sulphureus, respectively. Mature non-lactating cows in low body condition (LBC, n = 4) and high body condition (HBC, n = 4) received a single dose of dry ground lupine plant (2.0 g/kg of BW) via oral gavage. Lupinus leucophyllus (anagyrine) was dosed first; then after 21 d the same animals were dosed with L. sulphureus (ammodendrine). Blood samples were taken via jugular venipuncture 0 to 60 h after dosing. Serum anagyrine and ammodendrine concentrations were evaluated. The concentration of anagyrine was greater (P = 0.001) in the HBC group and peaked 2 h after dosing versus 12 h in LBC cows. Similarly for ammodendrine, the alkaloid concentration peaked at 3 h after dosing for the HBC group compared with 6 h for the LBC group (P = 0.001). Area under the curve tended to differ (P 相似文献   

Photosensitivity in South Africa. VI. The experimental induction of geeldikkop in sheep with crude steroidal saponins from Tribulus terrestris

Geeldikkop was induced in sheep by the oral administration of crude steroidal saponins from Tribulus terrestris. Two of the sheep developed typical lesions of geeldikkop, including birefringent crystalloid material in bile ducts and concentric periductal lamellar fibrosis. The clinical pathological changes in these sheep were also consistent with those of geeldikkop: aspartate transaminase and gamma-glutamyl transferase activities in the sera of both were elevated, and one had bilirubinaemia. A third sheep became photosensitive without typical lesions of geeldikkop in the liver or changes in the activities of liver enzymes before euthanasia. The findings of these trials are consistent with reports from abroad that ovine hepatogenous photosensitization, caused by Agave lechuguilla and Narthecium ossifragum, can be induced with crude saponins from the respective plants.     

Milk transfer of pyrrolizidine alkoloids in cattle.

A study was conducted to determine if pyrrolizidine alkaloids from Senecio jacobaea (tansy ragwort) are passed into milk of lactating cows. Four cows were given dried tansy ragwort via rumen cannula at a dosage of 10 g/kg/day for 2 weeks. Chemical assay of pyrrolizidine alkaloid content in the dried plants averaged 0.16% by weight. By use of thin-layer chromatography, 5 alkaloids were isolated from the plant materials. The only alkaloid isolated from the milk was jacoline. Condition of the cows and nursing calves was monitored via measurement of blood leukocyte count, and serum protein, albumin, and globulin content. Sorbitol dehydrogenase values and liver biopsy specimens were used to assess liver function. In the cows, marked changes were observed in blood leukocyte count, sorbitol dehydrogenase values, and liver biopsy findings. No changes of any type were observed in the calves. Pyrrolizidine alkaloid content of the milk ranged from 9.4 to 16.7 mug/100 ml of milk.     

Resistance of sheep to poisoning by The plant, Marticaria nigellifolia DC

The plant, Matricaria nigellifolia, was dosed to 2 sheep to reinvestigate whether or not sheep are susceptible to pushing disease ("stootsiekte"). Each sheep received a total dose of 370 g/kg of the milled, dried plant from a batch that had caused pushing disease in cattle when given at doses as low as 10 g/kg. Neither of the sheep developed clinical disease over the trial period of 60 days, and necropsies revealed no macro- or microscopical lesions. Sheep are apparently resistant to pushing disease, which supports previous findings.     

Toxicity and metabolism of pyrrolizidine alkaloids

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.     

An outbreak of subacute fasciolosis in Soay sheep: ultrasonographic biochemical and histological studies

A naturally occurring outbreak of subacute fasciolosis in a group of 17 seven-month-old Soay ram lambs was studied following the sudden death of two sheep. In addition to standard biochemical investigations, ultrasound examination of the liver and cranial abdominal cavity was undertaken. There was a significant positive linear correlation between liver weight and ultrasonographic determination of liver size (R=0.72, P<0.05). Ultrasonographic examination of the liver revealed multiple hyperechoic dots in the parenchyma giving a granular appearance to the hepatic texture in three sheep corresponding to the most advanced histopathological changes as determined by the size of the abscesses and their relatively mature fibrous capsules, and areas of hepatic necrosis. No distension of the bile duct system was noted nor was the gall bladder imaged. While serum concentrations of albumin, globulin and certain liver enzymes assisted in the diagnosis of subacute fasciolosis in sheep, only glutamate dehydrogenase, and gammaglutamyl transferase remained elevated four weeks after triclabendazole treatment.     

Efficacy of albendazole for prevention of fascioliasis in sheep

Daily doses of albendazole administered as a premix in the feed for 35 days were effective in preventing Fasciola hepatica infections in 17 sheep in three groups: 5 mg/kg/day (6 sheep) was 100% effective; 3 mg/kg/day (5 sheep) was 98% effective; and 1 mg/kg/day (6 sheep) was 42% effective. Infective cysts were given daily for 5 days during the first week of treatment, treatment was continued an additional 28 days, and sheep were necropsied 14 weeks after final cyst inoculation. There were no visible lesions in any livers of sheep given albendazole at the rate of 5 mg/kg/day or in three of five livers of sheep dosed at the rate of 3 mg/kg/day. Sheep treated with albendazole had a mean weight gain of 2.7 kg, 4.0 kg, and 4.0 kg greater than the controls for the dosages of 1, 3, and 5 mg/kg/day, respectively. Determination of bile duct damage by measurement of serum gamma-glutamyl transpeptidase activity at 9 weeks after final cyst inoculation revealed increases of 3.0X, 1.0X, and 1.1X for the dosages of 1, 3, and 5 mg/kg/day, respectively, and 2.3X for the control, as compared with 7 weeks after final cyst inoculation.     

A comparison of haemodynamic and vasoconstrictory responses in sheep with a toxic fraction from Pachystigma pygmaeum and with the plant material

ST-segment changes in the ECG, which are an indication of acute myocardial ischaemia, are obtained when a small quantity of an extract from dried Pachystigma pygmaeum is injected intravenously in sheep. When the fraction was injected subcutaneously, animals reached a crisis after about 5 h, with low values of stroke volumes and high values for pulmonary arterial pressures, pulmonary vascular resistances and heart rates. The haemodynamic changes are an indication of the development of pump failure of the heart. In sheep, injected subcutaneously with the toxic fraction, as well as for sheep dosed with plant material through rumen fistula, increased serum levels for thromboxane and increased or decreased levels for prostacycline were observed. The experimental results are interpreted as being an indication that these prostaglandines may be involved in the development of gousiekte by impeding cardiopulmonary function as a result of coronary and pulmonary vasoconstriction. The sudden death observed in some gousiekte sheep may be due to myocardial ischaemia and associated arrhythmias.     

Ovine hepatogenous photosensitivity caused by the plant Nidorella foetida (Thunb.) DC. (Asteraceae)

Following a field outbreak of hepatogenous photosensitivity in sheep, an identical condition was reproduced experimentally by dosing 2 sheep with green, homogenized, Nidorella foetida material, collected from the camp where the outbreak occurred. This is a rare, unpalatable, aromatic shrub found in swampy places in the south-western Cape Province. The main lesion was a hepatosis, characterized by peripheral coagulative necrosis and midzonal degeneration in the 2 acute cases and mild bile duct proliferation and hepatic regeneration in the more chronic field case. Botanical, toxicological, clinical and pathological data are given.     

Sunlight associated hyperthermia as a consistent and rapidly developing clinical sign in sheep intoxicated by St John's wort (Hypericum perforatum)

OBJECTIVE: To assess the usefulness of rectal temperature responses in Australian bred Merino sheep, following the oral administration of Hypericum perforatum (St John's wort), as an early indicator of Hypericum intolerance. DESIGN: Thirty-three Merino ewes were divided into three groups of 11. Each group was dosed with finely ground, dried, flowering growth stage H perforatum plant material at either 5.7, 4.0, or 2.85 g dry plant per kg live weight. This corresponded to 5.3, 3.7 and 2.65 mg hypericin per kg live weight, respectively. PROCEDURE: The sheep were dosed with a plant slurry by stomach tube and then exposed to bright sunlight for up to 5 h per day over successive days. Their clinical responses were observed and rectal temperature measured. RESULTS: Ingestion of H perforatum followed by exposure to bright sunlight frequently resulted in clinical signs attributable to skin irritation and central nervous effects, including an inappropriate increase in body temperature. A decrease in H perforatum ingestion from 5.7 to 2.85 g dry plant per kg live weight and a corresponding decrease in hypericin ingestion from 5.3 to 2.65 mg per kg live weight, was associated with a decrease in the severity of the clinical signs, including the severity of the hyperthermia. CONCLUSIONS: The rectal temperature rise in affected sheep is a reliable indicator of the early development of an adverse clinical effect. There appears to be an absolute requirement for exposure to bright sunlight before any effects of H perforatum will develop. A single dose of H perforatum remains potentially effective for up to 4 days. In the small group of Merino sheep tested a tolerance level for H perforatum, eaten at the flowering stage, of < 1% (plant wet weight) of body weight and a tolerance level for hypericin of < 2.65 mg per kg live weight, were demonstrated.     

Datura contamination of hay as the suspected cause of an extensive outbreak of impaction colic in horses

Datura poisoning of horses is extensively reviewed. An outbreak of intractable impaction colic affecting 18 of 83 horses was stopped by withdrawing dried tef hay contaminated with young Datura plants. The dried, botanically identified Datura stramonium and D. ferox contained respectively 0.15% mass/mass (m/m) hyoscyamine as well as 0.16% m/m hyoscine (scopolamine) and only hyoscine at a concentration of 0.11% m/m. Immature, unidentifiable plants resembling D. stramonium, contained 0.14% m/m and 0.12% m/m of the 2 respective tropane alkaloids. The outbreak was characterised by protracted and repeated colic attacks due to impaction of the large colon and/or caecum without any other anti-muscarinic signs. Comparative analyses of single specimens of dried seed of the 2 species collected from both fertilised and waste areas revealed that young South African Datura spp. had levels of tropane alkaloids comparable to those in the well-known toxic seed and were, consequently, equally toxic. The inherent danger of tef hay being contaminated with Datura is emphasised. To our knowledge this is the 1st field case of poisoning in horses ascribed to the vegetative parts of Datura spp.     

Clinical pathological changes in gousiekte, a plant-induced cardiotoxicosis of ruminants

Twenty sheep were dosed with either Pachystigma pygmaeum or Fadogia homblei belonging to the Rubiaceae. The experimentally-induced cardiotoxicoses were monitored by various clinical pathological parameters and heart function tests. Elevated AST (aspartate transaminase) activity in the serum proved to be a more reliable indicator of cardiac damage in gousiekte than either LD (lactate dehydrogenase) or CK (creatine kinase). Persistent increases of AST activity were recorded from c. 14 days after commencement of dosing, and this activity sometimes peaked as late as 30 days after the dosing had ceased. Tachycardia and diminished heart function were registered only terminally. Lesions of gousiekte were present in all the sheep that were exposed to the plants. In a field outbreak of P. pygmaeum, where 60 out of 90 sheep died, 14 out of the 15 animals examined had increased AST levels compared with none of the 15 controls. These results indicated that increased enzyme levels can be of use to identify affected animals during latency in a natural outbreak of gousiekte.