Hepatotoxic and nephrotoxic principles in Terminalia oblongata

A study was conducted to identify and characterise the toxic principle in Terminalia oblongata, commonly known as yellow-wood. Crude aqueous extracts of yellow-wood leaf were found to produce the same liver lesion in mice as has been reported in ruminants. The hepatotoxic fraction was isolated and identified as a hydrolysable vegetable tannin called punicalagin. When given orally, the dose required to produce toxicity was at least 20 times greater than when given intraperitoneally. Following a given dose of punicalagin, the onset and severity of liver necrosis was found to be related to the time interval after dosing. In addition to punicalagin, an unidentified nephrotoxic substance was found which was capable of producing avascular renal necrosis without liver necrosis.     

Tannic acid intoxication in sheep and mice

Acute tannic acid intoxication was studied in mice and sheep. In mice, following oral administration of 2.0 to 4.6 g of tannic acid kg-1 bodyweight, periacinar coagulative and haemorrhagic necrosis occurred in the liver. In sheep, following oral (8 g kg-1 bodyweight) administration of tannic acid, liver necrosis was not observed either histologically or detected biochemically, although transmission electron microscopy showed focal hepatocellular necrosis, steatosis and acicular crystal cleft formation. In sheep given tannic acid intraperitoneally (0.1 g kg-1 bodyweight), liver necrosis occurred and plasma sodium and glucose levels significantly (P < 0.05) decreased while packed cell volume and plasma aspartate aminotransferase, alkaline phosphatase, creatinine and bilirubin significantly (P < 0.01) rose. The results for blood-gas and acid-base determinations, blood haemoglobin and oxygenation showed significant increases in arterial blood methaemoglobin concentration (P < 0.05) and decreases in blood pH (P < 0.01) and oxyhaemoglobin concentration (P < 0.05) in sheep by 32 hours after oral dosing with 8 g of tannic acid kg-1 bodyweight. In sheep given tannic acid intraperitoneally, methaemoglobinaemia was not detected, but metabolic acidosis with a compensatory respiratory alkalosis occurred. Thus, it would appear that although tannic acid is hepatotoxic when given orally to mice or intraperitoneally to sheep, it does not produce renal or significant hepatic injury in sheep when given orally, but rather causes metabolic acidosis and methaemoglobinaemia.     

Experimental infection of sheep with bovine herpesvirus type-5 (BHV-5): acute and latent infection

We demonstrated that sheep are susceptible to acute and latent infection by bovine herpesvirus type-5 (BHV-5). Lambs inoculated intranasally with two South American BHV-5 isolates replicated the virus with titers up to 10(7.1) TCID50/ml for up to 15 days and showed mild signs of rhinitis. Four lambs in contact with the inoculated animals acquired the infection and excreted virus for up to seven days. One lamb developed progressive signs of neurological disease and was euthanized in extremis. Clinical signs consisted of tremors of the face, bruxism, ptyalism, incoordination, lateral flexion of the neck and head, circling, walking backwards, recumbency and paddling. The virus was detected in the anterior and posterior cerebrum, dorso- and ventro-lateral cortex, cerebellum, pons, midbrain and olfactory bulb. Viral nucleic acids were demonstrated in neurons and astrocytes of the anterior and ventro-lateral cortex by in situ hybridization. Histological changes consisting of non-suppurative meningitis, perivascular mononuclear cuffing, focal gliosis, neuronal necrosis and intranuclear inclusions were observed in the anterior cerebrum, ventro-lateral cortex and midbrain. Dexamethasone treatment at Day 50 pi resulted in reactivation of the latent infection and virus shedding in 13/16 (81%) of the lambs. Together with previous reports of BHV-5 antibodies in sheep, these findings show that sheep are fully susceptible to BHV-5 suggesting that infection by BHV-5 in sheep may occur naturally.     

Experimental prevention of bitterweed (Hymenoxys odorata) poisoning of sheep

To examine the effects on bitterweed toxicity of dietary factors known to increase thiol concentrations in the body, 36 lambs were fed one of the following diets (12 lambs/diet) for a minimum of 9 days prior to bitterweed administration: diet 1, 10% crude protein; diet 2, 20% crude protein, 0.5% methionine, 0.5% sodium sulfate, and 1,102 IU of vitamin E/kg; and diet 3, diet 2 with 0.5% ethoxyquin hydrochloride added. Four lambs fed each diet were euthanatized prior to bitterweed administration (initial euthanasia group). Four lambs fed each diet were administered bitterweed (0.68% hymenoxon, air-dried basis) at a rate of 0.25% of live weight for 5 consecutive days. The remaining four lambs on each diet served as unchallenged controls. In the initial euthanasia group, diet 2 increased extracellular blood thiol concentrations (1.12 vs 0.94 mg of SH/d1, P less than 0.10), rumen fluid thiol concentrations (4.46 vs 1.88 mg of SH/d1, P less than 0.05), and liver thiol concentrations (263.6 vs 109.3 micrograms SH/g of wet wt, P less than 0.05), compared with diet 1. Ethoxyquin hydrochloride (diet 3) reduced blood thiol concentrations (0.94 vs 1.12 mg of SH/dl, P less than 0.10) and liver thiol concentrations (151.6 vs 263.6 micrograms of SH/g of wet wt, P less than 0.05), compared with diet 2. Kidney thiols were unaffected by treatments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Protection by iron salts against sporidesmin intoxication in sheep

A number of iron compounds have been shown to protect sheep against the harmful effects of the facial eczema toxin, sporidesmin. Various salts were found to be effective; the oxidation state of the metal was not important although water-solubility did appear to be a prerequisite for prophylactic activity. The effect of iron salts was additive with that of zinc, and it is suggested that the protective action of these compounds results from their ability to inhibit the absorption of copper, consistent with the previously-proposed free-radical mechanism for sporidesmin toxicity.     

Protection by iron salts against sporidesmin intoxication in sheep

A number of iron compounds have been shown to protect sheep against the harmful effects of the facial eczema toxin, sporidesmin. Various salts were found to be effective; the oxidation state of the metal was not important although water-solubility did appear to be a prerequisite for prophylactic activity. The effect of iron salts was additive with that of zinc, and it is suggested that the protective action of these compounds results from their ability to inhibit the absorption of copper, consistent with the previously-proposed freeradical mechanism for sporidesmin toxicity.     

Effect of previous locoweed (Astragalus and Oxytropis species) intoxication on conditioned taste aversions in horses and sheep

Locoweed species (Astragalus and Oxytropis spp.) are a serious toxic plant problem for grazing livestock. Horses and sheep have been conditioned to avoid eating locoweed using the aversive agent LiCl. The objective of this study was to determine if previous locoweed intoxication affects food aversion learning in horses and sheep. Horses and sheep were divided into 3 treatment groups: control (not fed locoweed and not averted to a novel feed); locoweed-novel feed averted (fed locoweed and averted to a novel feed); and averted (not fed locoweed and averted to a novel feed). Animals in the locoweed-novel feed averted groups were fed locoweed during 2 periods of 21 and 14 d, respectively, with each feeding period followed by a 14-d recovery period. Animals were averted to a novel test feed at the end of the first locoweed-feeding period, and periodically evaluated for the strength and persistence of the aversion. During the first recovery period, locoweed-novel feed averted horses ate less (9.5% of amount offered) of the test feed than did control horses (99.8%) and did not generally differ from averted horses (0%). During recovery period 2, locoweed-novel feed averted horses (4.3%) differed (P = 0.001) in consumption (% of offered) of the test feed from controls (100%) and the averted group (0%). Locoweed-novel feed averted sheep differed (P = 0.001) from controls (14.4 vs. 99.5%, respectively, during recovery period 1), whereas locoweed-novel feed averted sheep did not differ (P > 0.50) from averted sheep (0.6%). During the second recovery period, control sheep (100%) differed (P < 0.05) from averted (0%) and locoweed-novel feed averted (12.2%) groups. Two intoxicated sheep (locoweed-novel feed averted) partially extinguished the aversion during the first recovery period, but an additional dose of LiCl restored the aversion. Two of 3 intoxicated horses had strong aversions that persisted without extinction; 1 horse in the locoweed-novel feed averted group had a weaker aversion. These findings suggest that horses and sheep previously intoxicated by locoweeds can form strong and persistent aversions to a novel feed, but in some animals, those aversions may not be as strong as in animals that were never intoxicated.     

Experimental infection of meadow voles (Microtus pennsylvanicus) with sheep scrapie

Meadow voles (Microtus pennsylvanicus) are permissive to chronic wasting disease (CWD) infection, but their susceptibility to other transmissible spongiform encephalopathies (TSEs) is poorly characterized. In this initial study, we intracerebrally challenged 6 meadow voles with 2 isolates of sheep scrapie. Three meadow voles acquired a TSE after the scrapie challenge and an extended incubation period. The glycoform profile of proteinase K-resistant prion protein (PrP^res) in scrapie-sick voles remained similar to the sheep inocula, but differed from that of voles clinically affected by CWD. Vacuolization patterns and disease-associated prion protein (PrP^Sc) deposition were generally similar in all scrapie-affected voles, except in the hippocampus, where PrP^Sc staining varied markedly among the animals. Our results demonstrate that meadow voles can acquire a TSE after intracerebral scrapie challenge and that this species could therefore prove useful for characterizing scrapie isolates.     

Experimental cross-infections of Haemonchus placei (Place, 1893) in sheep and cattle

To examine effects on biology and morphology, Haemonchus placei infections were propagated in cattle or sheep and infective larvae were introduced into the same or opposite host. Ovine source larvae had a geometric mean (GM) prepatent period of 26.5 days regardless of host species, compared to 30.6 days for bovine source larvae regardless of host species. Similarly, ovine source H. placei had a higher GM percentage establishment versus bovine source larvae (9.6% versus 3.4%) regardless of host species. The patent daily egg count for ovine source versus bovine source H. placei was 109.1 versus 50.0 FEC regardless of host species. Mean spicule length for ovine source H. placei was 492.5 microm while bovine source measured 496.5 microm. Mean female tail length for ovine source H. placei was 586.5 and 589.5 microm for bovine source H. placei. Using synlophe morphology, all worms that were measured were identified as H. placei. Sixty-three percent of females examined for vulvar flap morphology had knob-like vulvar flaps while the remaining 37% had linguiform vulvar flaps.