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Related Concept Videos

Toxicity Testing in Animals01:23

Toxicity Testing in Animals

79
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...
79
Drug Toxicity: Risk factors01:24

Drug Toxicity: Risk factors

66
Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
66

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Related Experiment Video

Updated: Mar 7, 2026

Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
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Profibrotic predictive toxicology in the lung.

Pooja Singh1, Rajesh Sinha1, Veena B Antony1

  • 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.

Frontiers in Pharmacology
|March 6, 2026
PubMed
Summary
This summary is machine-generated.

Mouse lung organoids (MiLO) accurately model pulmonary fibrosis caused by toxins and drugs. This 3D model helps study lung disease mechanisms and screen potential pro-fibrotic compounds, reducing animal testing.

Keywords:
3D culturemodelchemical induced toxicityenvironmental toxicantspredictive toxicologypulmonary toxicity

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Area of Science:

  • Pulmonary Medicine
  • Toxicology
  • 3D Organoid Technology

Background:

  • Interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis, cause gas exchange abnormalities and mortality.
  • Predictive, physiologically relevant models are crucial for studying ILDs and reducing animal use.
  • Three-dimensional (3D) lung organoids offer a complex, in vitro platform mimicking lung tissue structure and cellularity.

Purpose of the Study:

  • To evaluate mouse lung organoids (MiLO) as a model for assessing pulmonary toxicity from environmental toxicants and pharmaceutical agents.
  • To compare MiLOs' response to known fibrotic agents with in vivo benchmarks.
  • To validate MiLOs for mechanistic investigation and preclinical screening of pro-fibrotic compounds.

Main Methods:

  • Mouse lungs were processed to generate 3D lung organoids (MiLO).
  • MiLOs were characterized for cellular diversity and extracellular matrix (ECM) composition.
  • Organoids were exposed to cadmium (Cd), nitrofurantoin (NF), or amiodarone (AD) to induce fibrosis.
  • Fibrotic markers, gene expression, oxidative stress, and invasion were assessed in MiLOs and compared to in vivo data.

Main Results:

  • MiLOs successfully recapitulated native lung architecture, ECM, and fibrosis-related gene expression.
  • Cd-induced fibrosis in MiLOs mirrored in vivo findings, showing increased collagen deposition, oxidative stress, and profibrotic gene activation.
  • Drug treatments (NF, AD) induced hallmark fibrotic features in MiLOs, including elevated oxidative stress and upregulation of key fibrotic genes (e.g., Tgfb1, Col1a1).

Conclusions:

  • Mouse lung organoids effectively model drug- and toxin-induced pulmonary fibrosis.
  • MiLOs provide a powerful platform for mechanistic studies of lung fibrosis.
  • This model aids in preclinical screening of compounds with potential pro-fibrotic effects, reducing reliance on animal models.