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Toxicity Testing in Animals01:23

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Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...
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RNA-Seq analysis implicates detoxification pathways in ovine mycotoxin resistance.

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Mycotoxin exposure causes liver damage via oxidative stress. However, ruminants with higher detoxification gene expression and amplified Wnt signaling show resistance to mycotoxins.

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Area of Science:

  • Veterinary Medicine
  • Toxicology
  • Molecular Biology

Background:

  • Mycotoxin-induced liver damage is linked to oxidative stress.
  • Limited molecular studies exist on animal mycotoxicoses.
  • Ruminants are susceptible to mycotoxin-related health issues.

Purpose of the Study:

  • Investigate molecular mechanisms of mycotoxin exposure in ruminants.
  • Utilize RNA-seq to analyze hepatic gene expression changes.
  • Correlate gene expression with pathological outcomes and resistance.

Main Methods:

  • Assembled a de novo reference transcriptome for ruminants.
  • Employed RNA-sequencing (RNA-seq) to profile gene expression.
  • Analyzed in vivo hepatic gene expression in response to mycotoxin challenge.

Main Results:

  • Oxidative stress-related gene expression differed between susceptible and resistant animals.
  • Detoxification genes, including cytochrome P450 family members, were upregulated in resistant animals.
  • Amplified Wnt signaling pathway activity was observed in resistant animals due to suppressed Wnt inhibitors.

Conclusions:

  • Mycotoxin resistance in ruminants is associated with enhanced detoxification capabilities.
  • Upregulated detoxification and Wnt signaling pathways are key to mycotoxin tolerance.
  • Understanding these pathways can inform strategies for managing mycotoxicoses.