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Sperm Collection and Computer-Assisted Sperm Analysis in the Teleost Model Japanese Medaka (<em>Oryzias latipes</em>)

Japanese medaka (Oryzias latipes) is a teleost fish and&#160;an emerging vertebrate model for ecotoxicology, developmental, genetics, and physiology ...

Norwegian University of Life Sciences

Deoxynivalenol (DON) is one of the most prevalent Fusarium mycotoxins in grain and can cause economic losses in pig farming due to reduced feed consumption and lower weight gains. Biodetoxification of mycotoxins using bacterial strains has been a focus of research for many years. However, only a few in vivo studies have been conducted on the effectiveness of microbial detoxification of fusariotoxins. This study was therefore aimed at investigating the effect of a feed additive containing the bacterial strain Coriobacteriaceum DSM 11798 (the active ingredient in Biomin® BBSH 797) on growth performance and blood parameters, as well as uptake and metabolism of DON, in growing pigs. Forty-eight crossbred (Landrace-Yorkshire/Duroc-Duroc) weaning pigs were fed with pelleted feed made from naturally contaminated oats, with DON at four concentration levels: (1) control diet (DON < 0.2 mg kg), (2) low-contaminated diet (DON = 0.92 mg kg), (3) medium-contaminated diet (DON = 2.2 mg kg) and (4) high-contaminated diet (DON = 5.0 mg kg) and equivalent diets containing DSM 11798 as feed additive. During the first 7 days of exposure, pigs in the highest-dose group showed a 20-28% reduction in feed intake and a 24-34% reduction in weight gain compared with pigs in the control and low-dose groups. These differences were levelled out by study completion. Towards the end of the experiment, dose-dependent reductions in serum albumin, globulin and total serum protein were noted in the groups fed with DON-contaminated feed compared with the controls. The addition of DSM 11798 had no effect on the DON-related clinical effects or on the plasma concentrations of DON. The ineffectiveness of the feed additive in the present study could be a consequence of its use in pelleted feed, which might have hindered its rapid release, accessibility or detoxification efficiency in the pig's gastrointestinal tract.

Effects and biotransformation of the mycotoxin deoxynivalenol in growing pigs fed with naturally contaminated pelleted grains with and without the addition of Coriobacteriaceum DSM 11798.

Deoxynivalenol (DON) is the most prevalent mycotoxin in cereals worldwide. It can cause adverse health effects in humans and animals, and maximum levels in food and feed have been implemented by food authorities based on risk assessments derived from estimated intake levels. The lack of human toxicokinetic data such as absorption, distribution, and elimination characteristics hinders the direct calculation of DON plasma levels and exposure. In the present study, we have, therefore, used in vitro-to-in vivo extrapolation of depletion constants in hepatic microsomes from different species and allometric scaling of reported in vivo animal parameters to predict the plasma clearance [0.24 L/(h × kg)] and volume of distribution (1.24 L/kg) for DON in humans. In addition, we have performed a toxicokinetic study with oral and intravenous administration of DON in pigs to establish benchmark parameters for the in vitro extrapolation approach. The determined human toxicokinetic parameters were then used to calculate the bioavailability (50-90%), maximum concentration, and total exposure in plasma, and urinary concentrations under consideration of typical DON levels in grain-based food products. The results were compared to data from biomonitoring studies in human populations.

Prediction of deoxynivalenol toxicokinetics in humans by in vitro-to-in vivo extrapolation and allometric scaling of in vivo animal data.

The most prevalent  mycotoxin in grains is deoxynivalenol (DON). Contamination of swine feed with DON can result in reduced consumption and poor growth performance. Gestating and lactating sows need sufficient feed intake for fetus development during late gestation and milk production and body maintenance during lactation. Therefore, there is considerable concern in modern piglet production about the effects of DON contamination in sow feed. Most previous studies in sows have been done under experimental conditions, with DON levels ≥2.8 mg/kg feed. The aim of the current field trial was to investigate the effects of feeding grains that are naturally contaminated with more realistic levels of DON on sows during late gestation and lactation.

Effects of feeding naturally contaminated deoxynivalenol diets to sows during late gestation and lactation in a high-yield specific pathogen-free herd.

Deoxynivalenol (DON) contamination of feed may result in reduced growth, feed refusal, immunosuppression, and health problems in swine. Piglets can be exposed to DON via placenta before birth and via milk during lactation. The extent of early-life exposure of piglets to DON is, however, not fully known. This study was therefore aimed at investigating DON uptake in sows fed with naturally contaminated diets, DON transfer across placenta during late gestation, and transfer of DON to piglets via colostrum and milk. Forty-four crossbred sows were evaluated from day 93 ± 1 of gestation until weaning of piglets and fed with feed made from naturally DON-contaminated oats at three concentration levels: (1) control (DON < 0.2 mg/kg), (2) DON level 1 (1.4 mg DON/kg), and (3) DON level 2 (1.7 mg DON/kg). The transfer of DON to the piglets was evaluated in 15 sows, with repeated sampling of blood and milk from the sows and blood samples from five piglets of each litter. The piglet/sow plasma DON ratio and milk/plasma (M/P) DON ratio in sows were calculated to estimate the degree of transfer. Piglet/sow plasma ratios were 2.14 at birth, 2.30 within 12⁻36 h after parturition, 0.08 on day 7, 0.16 on day 21, and 0.20 at weaning. M/P ratios were 0.92, 1.11, 0.94, 1.21, and 0.90, respectively. The results indicate that DON is efficiently transferred across placenta and into milk. However, the low piglet/sow plasma ratios at mid-lactation to weaning indicate that the piglets were most strongly exposed to DON in early life, despite the high M/P ratios and efficient secretion of DON in milk throughout the entire lactation.

Transfer of Deoxynivalenol (DON) through Placenta, Colostrum and Milk from Sows to Their Offspring during Late Gestation and Lactation.

The mycotoxin deoxynivalenol (DON) has a high global prevalence in grain-based products. Biomarkers of exposure are detectable in most humans and farm animals. Considering the acute emetic and chronic anorexigenic toxicity of DON, maximum levels for food and feed have been implemented by food authorities. The tolerable daily intake (TDI) is 1 µg/kg body weight (bw)/day for the sum of DON and its main derivatives, which was based on the no-observed adverse-effect level (NOAEL) of 100 µg DON/kg bw/day for anorexic effects in rodents. Chronic exposure to a low-DON dose can, however, also cause inflammation and imbalanced neurotransmitter levels. In the present study, we therefore investigated the impact of a 2-week exposure at the NOAEL in mice by performing behavioural experiments, monitoring brain activation by c-Fos expression, and analysing changes in the metabolomes of brain and serum. We found that DON affected neuronal activity and innate behaviour in both male and female mice. Metabolite profiles were differentiable between control and treated mice. The behavioural changes evidenced at NOAEL reduce the safety margin to the established TDI and may be indicative of a risk for human health.

Behavioural and metabolomic changes from chronic dietary exposure to low-level deoxynivalenol reveal impact on mouse well-being.

Sickness can change our mood for the worse, leaving us sad, lethargic, grumpy and less socially inclined. This mood change is part of a set of behavioral symptoms called sickness behavior and has features in common with core symptoms of depression. Therefore, the physiological changes induced by immune activation, for example following infection, are in the spotlight for explaining mechanisms behind mental health challenges such as depression. While humans may take a day off and isolate themselves until they feel better, farm animals housed in groups have only limited possibilities for social withdrawal. We suggest that immune activation could be a major factor influencing social interactions in pigs, with outbreaks of damaging behavior such as tail biting as a possible result. The hypothesis presented here is that the effects of several known risk factors for tail biting are mediated by pro-inflammatory cytokines, proteins produced by the immune system, and their effect on neurotransmitter systems. We describe the background for and implications of this hypothesis.

Article	Year
Effects and biotransformation of the mycotoxin deoxynivalenol in growing pigs fed with naturally contaminated pelleted grains with and without the addition of Coriobacteriaceum DSM 11798. Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment\| PubMed ID: 29701502	2018
Prediction of deoxynivalenol toxicokinetics in humans by in vitro-to-in vivo extrapolation and allometric scaling of in vivo animal data. Archives of toxicology\| PubMed ID: 29774371	2018
Effects of feeding naturally contaminated deoxynivalenol diets to sows during late gestation and lactation in a high-yield specific pathogen-free herd. Porcine health management\| PubMed ID: 30410782	2018
Transfer of Deoxynivalenol (DON) through Placenta, Colostrum and Milk from Sows to Their Offspring during Late Gestation and Lactation. Toxins\| PubMed ID: 30518156	2018
Behavioural and metabolomic changes from chronic dietary exposure to low-level deoxynivalenol reveal impact on mouse well-being. Archives of toxicology\| PubMed ID: 31065730	2019
A Proposed Role for Pro-Inflammatory Cytokines in Damaging Behavior in Pigs. Frontiers in veterinary science\| PubMed ID: 33134341	2020

Amin Sayyari

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