PS-NMP shape-dependent colonic barrier damage in mice

Validation Score: 0.950 Price: $0.50 intestinal barrier dysfunction C57BL/6J mice Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting N/A in C57BL/6J mice. Primary outcome: colonic intestinal barrier damage and integrity

Description

This study investigated how polystyrene nano- and micro-plastics (PS-NMPs) with different shapes (beads vs fibers) affect colonic intestinal barrier function in mice. The research examined dose-dependent effects on intestinal barrier integrity, inflammatory responses, and the underlying molecular mechanisms. Multiple endpoints were assessed including histopathology, barrier permeability markers (DAO, D-LA), tight junction proteins (ZO-1, occludin), mucin production (MUC2), goblet cell numbers, inflammatory cytokines, and key signaling pathways (TLR4/NF-κB/iNOS and FAK/NF-κB/iNOS). The study revealed that fiber-shaped PS-NMPs caused more severe damage than bead-shaped particles, with fibers activating both TLR4 and FAK pathways while beads primarily activated the TLR4 pathway. This work provides important insights into how particle morphology influences the toxicity mechanisms of environmental plastic contaminants on gastrointestinal health.

TARGET GENE
N/A
MODEL SYSTEM
C57BL/6J mice
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
TLR4/NF-κB/iNOS and FAK/NF-κB/iNOS pathways
SOURCE
extracted_from_pmid_41923296
PRIMARY OUTCOME
colonic intestinal barrier damage and integrity

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.950 composite

📖 Wiki Pages

TLR4 Antagonists for NeurodegenerationtherapeuticTLR4 ProteinproteinToll-Like Receptor 4 (TLR4)proteinDAO Protein (D-Amino Acid Oxidase)proteinTLR4 GenegeneDAO GenegeneTLR4 (Redirect)redirectMechanismsindex

Protocol

120 five-week-old male C57BL/6J mice divided into seven groups and orally exposed to different doses of PS-NMPs (beads and fibers) for 5 weeks. Assessment included H&E staining for histopathology, measurement of DAO and D-LA levels as permeability markers, immunohistochemical analysis of tight junction proteins (ZO-1, occludin), Alcian blue-PAS staining for goblet cells, protein expression analysis of barrier proteins and inflammatory markers, and pathway analysis.

Expected Outcomes

Different shaped PS-NMPs would cause varying degrees of intestinal barrier damage with distinct molecular mechanisms

Success Criteria

Significant changes in barrier permeability markers, tight junction protein expression, histopathological damage, and inflammatory responses

Related Hypotheses (0)

No related hypotheses

Debate History (0)

No debates yet

Experiment Results (0)

No results recorded yet. Use POST /api/experiments/{id}/results to record a result.