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Arterial Responses to Acute Low-Level Ergot Exposure in Hereford Cows.

ABSTRACT: Ergot alkaloids are toxic secondary metabolites produced by the fungus Claviceps purpurea that contaminate cereal grains. Current Canadian standards allow 2 to 3 parts per million of ergot alkaloids in animal feed. The purpose of this study was to determine whether hemodynamic parameters were altered when beef cows were fed permissible levels of ergot alkaloids (i.e., <3 ppm) on a short-term basis. A dose-response relationship between ergot alkaloid concentration and hemodynamic changes in caudal (coccygeal), median sacral, and internal iliac arteries was hypothesized. Beef cows were randomly allocated to: Control (<15 ?g total ergot alkaloids/kg dry matter), Low (132 ?g/kg), Medium (529 ?g/kg), and High (2115 ?g/kg) groups (n = 4 per group). Animals were fed 8.8 kg of dry matter daily for 4 days (pre-treatment), 7 days (treatment), and 4 days (post-treatment). The caudal, median sacral, and internal iliac arteries were examined daily using ultrasonography in B-mode and Doppler (color and spectral) mode and hemodynamics endpoints were analyzed by repeated measures mixed model analyses. Caudal artery diameter decreased in the Medium (p = 0.004) and High (p < 0.001) groups compared to pre-treatment values and the pulsatility index increased (p ? 0.033) in all ergot treatments during the post-exposure period compared to the Control group. Blood volume per pulse (mL) and blood flow (mL/min) through the caudal artery during the treatment period were reduced in the Medium (-1.0 mL reduction; p ? 0.004) and High (-1.1 mL p ? 0.006) groups compared to pre-treatment values. The median sacral artery diameter decreased in the Medium (p = 0.006) and High (p = 0.017) treatments compared to the Control group. No differences were detected in any hemodynamic endpoints for the internal iliac artery except changes in pulse rate (p = 0.011). There was no treatment (p > 0.554) or Treatment*Time interaction (p > 0.471) for plasma prolactin concentration or body temperature. In conclusion, alterations in caudal artery hemodynamics were detected when cows were fed 529 and 2115 ?g ergot alkaloids per kg dry matter per day for 1 week. The caudal artery was more sensitive to ergot alkaloids than the median sacral and internal iliac arteries. Our results partially support the hypothesis of a dose-response effect of ergot alkaloids in feed on hemodynamics.

SUBMITTER: Cowan VE

PROVIDER: S-EPMC6198079 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Arterial Responses to Acute Low-Level Ergot Exposure in Hereford Cows.

Cowan Vanessa Elizabeth VE Neumann Alex A McKinnon John J Blakley Barry Raymond BR Grusie Taylor Jayne TJ Singh Jaswant J

Frontiers in veterinary science 20181016

Ergot alkaloids are toxic secondary metabolites produced by the fungus <i>Claviceps purpurea</i> that contaminate cereal grains. Current Canadian standards allow 2 to 3 parts per million of ergot alkaloids in animal feed. The purpose of this study was to determine whether hemodynamic parameters were altered when beef cows were fed permissible levels of ergot alkaloids (i.e., <3 ppm) on a short-term basis. A dose-response relationship between ergot alkaloid concentration and hemodynamic changes i ...[more]

PMID: 30386784

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Project description:Ergot alkaloids are vasoconstrictors frequently detected in low concentrations in livestock feed. The Canadian Food Inspection Agency permits up to 3,000 μg ergot alkaloids per kg cattle feed. The objective of this study was to examine the effects of feeding low concentrations of ergot alkaloids over 9-weeks on vascular dynamics in the caudal and internal iliac arteries of beef cows. A relationship between ergot alkaloid concentration in feed and hemodynamic changes in the caudal and internal iliac arteries was hypothesized. Periparturient beef cows were randomized into four groups and group fed mixed rations containing <15 μg ergot alkaloids per kg of dry matter intake (Control, n = 9), 48 μg/kg (Low, n = 9), 201 μg/kg (Medium, n = 8), and 822 μg/kg (High, n = 6). Three experimental periods comprised the study: pre-treatment (2 weeks), treatment (9 weeks), and post-treatment (3 weeks). B-mode and Doppler ultrasonography was performed weekly to measure hemodynamic endpoints. Plasma prolactin concentrations and rectal temperatures were measured weekly. Caudal artery diameter decreased (Treatment*Experimental Period i.e., Tx*EP, p < 0.001) by 14% in the High group during the treatment period. Reductions (Tx*EP, p < 0.001) in caudal artery blood flow (37%, 29%) and blood volume per pulse (29%, 11%) were recorded during the treatment period in the High and Medium groups. Internal iliac artery diameter and blood flow decreased (Tx*EP, p ≤ 0.004) by 13% and 40% during the treatment period in the Medium group. Moderate reductions (Tx*EP, p ≤ 0.042; 12-25%) in the mean blood velocity during the treatment and post-treatment periods and decreases (Tx*EP, p ≤ 0.01; 12-17%) in the peak systolic velocity of both arteries during the post-treatment period were also detected. Prolactin did not change in any group during the treatment period (p = 0.462). Rectal temperatures were within the normal physiological range for beef cows. In conclusion, we documented moderate vasoconstriction in the caudal artery and the internal iliac artery in cows fed 201-822 μg ergot alkaloids per kg of dry matter intake for 9-week period near parturition. The pattern of alterations was similar between the caudal and internal iliac arteries. Results of this study suggest that feeding up to 822 μg/kg produce reversible pharmacological changes in beef cow vasculature and warrant reconsideration of current regulations for cattle.

Project description:Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and putative developmental neurotoxicant in humans. The acute toxicity of CPF is elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related (0.1, 0.5, 1 and 2mg/kg) gene expression profiles and changes in cell signaling pathways 24h following acute CPF exposure in 7-day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following either one of the four CPF dosages studied (546, 505, 522, and 3,066 genes with 0.1, 0.5, 1.0 and 2.0mg/kg CPF). Genes were grouped according to dose-related expression patterns using K-means clustering while gene networks and canonical pathways were evaluated using Ingenuity Pathway Analysis®. Twenty clusters were identified and differential expression of selected genes was verified by RT-PCR. The four largest clusters (each containing from 276 to 905 genes) constituted over 50% of all differentially expressed genes and exhibited up-regulation following exposure to the highest dosage (2mg/kg CPF). The total number of gene networks affected by CPF also rose sharply with the highest dosage of CPF (18, 16, 18 and 50 with 0.1, 0.5, 1 and 2mg/kg CPF). Forebrain cholinesterase (ChE) activity was significantly reduced (26%) only in the highest dosage group. Based on magnitude of dose-related changes in differentially expressed genes, relative numbers of gene clusters and signaling networks affected, and forebrain ChE inhibition only at 2mg/kg CPF, we focused subsequent analyses on this treatment group. Six canonical pathways were identified that were significantly affected by 2mg/kg CPF (MAPK, oxidative stress, NFΚB, mitochondrial dysfunction, arylhydrocarbon receptor and adrenergic receptor signaling). Evaluation of different cellular functions of the differentially expressed genes suggested changes related to olfactory receptors, cell adhesion/migration, synapse/synaptic transmission and transcription/translation. Nine genes were differentially affected in all four CPF dosing groups. We conclude that the most robust, consistent changes in differential gene expression in neonatal forebrain across a range of acute CPF dosages occurred at an exposure level associated with the classical marker of OP toxicity, AChE inhibition. Disruption of multiple cellular pathways, in particular cell adhesion, may contribute to the developmental neurotoxicity potential of this pesticide.

Project description:Previous research has shown that livestock exposed to ergot alkaloids results in decreased vasoactivity of gastrointestinal and peripheral vasculature. Little is known regarding the effect ergot alkaloid exposure during gestation may have on vasculature supporting the fetus. The objective of this study was to evaluate contractile responses of uterine and umbilical arteries collected from ewes consuming ergot alkaloids during gestation. On day 35 of gestation, 36 Suffolk ewes (78.24 ± 9.5 kg) were assigned to endophyte-infected (E+) or endophyte-free (E-) tall fescue seed treatments that were fed either throughout or switched on day 86 of gestation, creating four seed treatments E+E+, E+E-, E-E+, and E-E-. Ewes were fed E+ tall fescue seed to provide 1.77 mg of total ergovaline ⋅ hd-1 ⋅ d-1 with E- ewes receiving the same quantity of E- seed. Gestation was terminated on day 133, and sections of uterine artery and umbilical cord were surgically collected. Only collections from 28 ewes (n = 7/treatment) were of sufficient viability to proceed with the contractility experiments. Arteries were cleaned, sliced into 2-mm cross sections, and suspended in multi-myograph chambers containing 5 mL of continuously oxygenated Krebs-Henseleit buffer. Vessels were exposed to increasing concentrations (5 × 10-8 to 1 × 10-4 M) of norepinephrine, serotonin, ergotamine, and ergovaline (5 × 10-9 to 1 × 10-5M; extract of tall fescue seed) in 15-min intervals. Increasing concentrations of norepinephrine generated a contractile response by the uterine artery (P < 0.05), but no response in the umbilical artery. Increasing concentrations of serotonin resulted in negligible responses in uterine preparations, whereas umbilical artery preparations were responsive (P < 0.05) to serotonin. Ewes receiving E+E+ and E-E+ treatments had decreased vasoactivity in umbilical arteries to serotonin with a dextral shift in concentrations where the response curve initiated (P < 0.05). Interestingly, uterine arteries were not responsive to exposure to ergotamine or ergovaline, whereas umbilical arteries were responsive (P < 0.05). Umbilical arteries collected from ewes receiving E-E- and E+E- were more vasoactive to ergot alkaloids (P < 0.05) than other treatments. These findings indicate that maternal blood supply to the placenta appears protected from negative effects of ergot alkaloids; however, umbilical vasculature is not, and this could adversely influence fetal growth.

Dataset Information

Arterial Responses to Acute Low-Level Ergot Exposure in Hereford Cows.

Publications

Arterial Responses to Acute Low-Level Ergot Exposure in Hereford Cows.

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