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Related Concept Videos

Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

154
In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
154

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Related Experiment Video

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Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats
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Hepatic Transcriptomic Patterns in the Neonatal Rat After Pentabromodiphenyl Ether Exposure.

June K Dunnick1, Keith R Shockley2, Daniel L Morgan1

  • 1Toxicology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.

Toxicologic Pathology
|December 13, 2019
PubMed
Summary

Neonatal exposure to PBDEs like DE-71 and PBDE-47 alters rat liver gene expression, indicating potential toxicity and carcinogenicity. These early transcriptomic changes serve as crucial indicators for risk assessment.

Keywords:
PBDE mixture (DE-71)PBDE-47liver toxicityliver transcriptomic patternspentabromodiphenyl etherthyroxine (T4)

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Area of Science:

  • Toxicology
  • Environmental Health
  • Genomics

Background:

  • Human exposure to polybrominated diphenyl ethers (PBDEs) occurs in utero and during lactation.
  • PBDEs are flame retardants with potential health risks.

Purpose of the Study:

  • To investigate if neonatal hepatic transcriptomic alterations from PBDE exposure predict longer-term toxicity and carcinogenicity.
  • To assess the utility of early toxicogenomic indicators for risk evaluation.

Main Methods:

  • Wistar Han rat dams were exposed to DE-71 or PBDE-47 from gestation day 6 to postnatal day 4.
  • Hepatic gene expression and plasma thyroxine (T4) levels were analyzed in pups.

Main Results:

  • Decreased plasma T4 levels were observed in exposed pups.
  • Upregulation of transcripts for CYPs, conjugation enzymes, Nrf2, and ABC transporters in the liver.
  • Transcriptomic alterations indicated early signs of oxidative stress and metabolic changes.

Conclusions:

  • Neonatal PBDE exposure induces hepatic transcriptomic changes that serve as early indicators of potential toxicity and carcinogenicity.
  • PBDE-47 showed a lower transcriptional benchmark dose than the PBDE mixture.
  • Toxicogenomic data can help prioritize chemicals for further risk assessment.