LPS-induced Acute Lung Injury

Acute LPS-induced pulmonary injury in mice

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Compliance

Non-GLP compliant. The study is for a discovery-phase preclinical project.

Purpose of the Study

The purpose of this study is to evaluate development of acute lung injury in mice in terms of endpoint measurements of TNFα, IL-6, myeloperoxidase activity, as well as total cells and proportion of neutrophils in brochoalveolar fluid (BALF).

Test System

Male C57BL/6 mice (Charles River Laboratories) weighing between 20 and 25 g at the time of study initiation will be used in the study.

Methodology

Male C57BL/6 mice weighing between 20 and 25 g will be given food and water ad libitum. Animals will be housed in groups of 3. The animals will be randomly assigned to each experimental group.

Group 1. Control mice (5 mice)
Group 2. LPS + vehicle (8 mice)
Group 3. LPS + test article (8 mice)

Endpoints

  • Arterial oxygen saturation and heart rate
  • Lung oedema
  • Lung histology (H&E staining)
  • Total cell count and numbers of neutrophils determined from the BALF pellets for each mouse and expressed as number of cells per mL BAL fluid
  • TNFα and IL-6 protein quantification and myeloperoxidase (MPO) activity measured in the BALF supernatant of each mouse and expressed as the concentration per mL BAL fluid, or units MPO.

Study Timeline

  • One week to finalize the protocol/formulation
  • Experiments can be initiated the following week
  • Six animals can be experimented upon per day
  • BALF analysis produces results in the week of BALF collection
  • Three weeks for histopathological analysis following collection of the samples.

Reporting

  • Non-audited report two weeks following the last measurement if no histopathology
  • Non-audited report with histological analysis results available two weeks after the histology slides become available if histopathology is selected.