No abstract

IntroductionPhotosensitization is a common clinical sign in cows suffering from liver damage caused by the mycotoxin sporidesmin. This disease, called facial eczema (FE), is of major importance in New Zealand. Current techniques for diagnosing animals with subclinical sporidesmin-induced liver damage (i.e. without photosensitization) are nonspecific. In addition, little is known of the mechanisms involved in sporidesmin resistance, nor the early effects seen following low-dose sporidesmin intoxication.ObjectiveThe objective of this study was to identify individual metabolites or metabolic profiles that could be used as serum markers for early stage FE in lactating cows.MethodsResults are presented from a 59-day sporidesmin challenge in Friesian-cross dairy cows. Serum metabolite profiles were obtained using reversed phase ultra-performance liquid chromatography (UPLC) electrospray ionization mass spectrometry (MS) and UPLC tandem MS. Multivariate and time series analyses were used to assess the data.ResultsStatistical analysis, both with and without the temporal component, could distinguish the profiles of animals with clinical signs from the others, but not those affected subclinically. An increase in the concentrations of a combination of taurine- and glycine-conjugated secondary bile acids (BAs) was the most likely cause of the separation. This is the first time that MS methods have been applied to FE and that bile acids changes have been detected in cattle exposed to sporidesmin.ConclusionsIt is well known that BA concentrations increase during cholestasis due to damage to bile ducts and leakage of the bile. This is the first study to investigate metabolomic changes in serum following a sporidesmin challenge. Further work to establish the significance of the elevation of individual BAs concentrations in the serum of early-stage sporidesmin-poisoned cows is necessary.Electronic supplementary materialThe online version of this article (10.1007/s11306-018-1358-4) contains supplementary material, which is available to authorized users.

Cattle occasionally develop brassica-associated liver disease (BALD) and photosensitisation when grazing turnip or swede (Brassica spp.) forage crops. The liver toxin in these brassica varieties has yet to be discovered. Progoitrin is the dominant glucosinolate in incriminated crops. Apart from goitrin, progoitrin hydrolysis yields the nitrile, 1-cyano-2-hydroxy-3-butene (CHB), and the epithionitrile, 1-cyano-2-hydroxy-3,4-epithiobutane (CHEB). The two compounds were custom-synthesised. In a small pilot trial, New Zealand White rabbits were given either CHB or CHEB by gavage. Single doses of 0.75 mmol/kg of CHB or 0.25 mmol/kg of CHEB were subtoxic and elicited subclinical effects. Higher doses were severely hepatotoxic, causing periportal to massive hepatic necrosis associated with markedly elevated serum liver biomarkers often resulting in severe illness or death within 24 h. The possibility that one or both of these hepatotoxic nitriles causes BALD in cattle requires further investigation.

AIMS To investigate the effects on milk yield in lactating dairy cows of a single dose of sporidesmin, and to categorise the responses based on clinical signs and differing degrees of liver damage, as assessed by activities of γ-glutamyl transferase (GGT) and post-mortem liver histopathology. METHODS Adult lactating dairy cows (n=17) were given a single intra-ruminal dose of 0.24 mg/kg of sporidesmin dissolved in ethanol and diluted in water on Day 0; an additional three cows served as untreated controls. Weekly serum samples were collected between Days -14 and 42 and analysed for activities of GGT. Milk yields were measured daily over the same period. Cows were subjected to euthanasia due to severe clinical signs (n=2) or were slaughtered at the end of the trial. Samples of livers were examined histologically and were scored for lesions on a scale from 0 (normal) to 3 (severe). Based on GGT activities and clinical observations, cows that were treated with sporidesmin were categorised as non-responders (no clinical signs and normal GGT), subclinical (elevated GGT and no clinical signs) or clinical. Outcomes were compared between these three groups and control cows using generalised additive models. RESULTS Seven cows were classified as clinical, and had median liver scores of 22 (95% CI=20.6-23.4), six were subclinical with median liver scores of 8.7 (95% CI=3.8-13.5) and four were non-responders with median liver scores of 2.5 (95% CI=1.2-4.3). Median liver scores for the three control cows were 1 (95% CI=-0.8-2.1). Activities of GGT increased in subclinical and clinical cows around Day 7. The milk yield of all cows treated with sporidesmin, including non-responder cows, started to decrease on Day 1, and reached a nadir (a drop of between 9 and 85%) on Day 7. CONCLUSIONS AND CLINICAL RELEVANCE It is likely that the overall effects of sporidesmin consumption on milk production by the national herd in New Zealand are hugely underestimated, especially considering its effects on non-responder and subclinical cows as shown in this trial. In view of the results presented here, the authors are suggesting a change to the definition of response to sporidesmin from non-responder, subclinical, and clinical, to subclinical-low, subclinical-high, and clinical, when measuring a combination of GGT activities, clinical signs and milk yields during facial eczema-risk seasons (summer-autumn).

Cattle occasionally develop brassica-associated liver disease (BALD) and photosensitisation when grazing turnip or swede (Brassica spp.) forage crops. The liver toxin in these brassica varieties has yet to be discovered. Progoitrin is the dominant glucosinolate in incriminated crops. Apart from goitrin, progoitrin hydrolysis yields the nitrile, 1-cyano-2-hydroxy-3-butene (CHB), and the epithionitrile, 1-cyano-2-hydroxy-3,4-epithiobutane (CHEB). The two compounds were custom-synthesised. In a small pilot trial, New Zealand White rabbits were given either CHB or CHEB by gavage. Single doses of 0.75 mmol/kg of CHB or 0.25 mmol/kg of CHEB were subtoxic and elicited subclinical effects. Higher doses were severely hepatotoxic causing periportal to massive hepatic necrosis associated with markedly elevated serum liver biomarkers often resulting in severe illness or death within 24 h. The possibility that one or both of these hepatotoxic nitriles causes BALD in cattle requires further investigation.