# Evaluation of a peptide that inhibits  the activation of NOX2 and the generation of reactive oxygen species in protection against acute lung injury

> **NIH NIH R41** · PEROXITECH, LLC · 2020 · $299,866

## Abstract

SUMMARY:
Acute lung injury (ALI) is a devastating complication of sepsis,viral and bacterial
pneumonias, severe trauma with or without major blood loss, acid aspiration and other
conditions that affect the lung either primarily or secondarily.This relatively common
syndrome (~200,000 cases per yr in the US) currently has an overall mortality rate of
~40%. Lung inflammation associated with the production of reactive oxygen species
(ROS) is an important contributor to the ALI syndrome. We have shown that activation of
NADPH oxidase, type 2 (NOX2), the major source of ROS in lungs, requires the PLA2
activity of peroxiredoxin 6 (Prdx6) and have recently identified a 9 amino acid peptide
that binds to Prdx6 and inhibits its PLA2 activity; we have named this Prdx6 inhibitory
peptide (PIP-2). PIP-2 encapsulated in liposomes and administered intratracheally (IT)
to mice inhibited the lung generation of ROS by >80% for 24 h. PIP-2 administered 12-16
h after low dose LPS (given IT) markedly decreased lung inflammation and tissue
oxidative injury when examined at 24 h and greatly decreased mortality (from 100% to
28%) after high dose LPS. PIP-2 also markedly decreased mouse mortality after
intraperitoneal LPS as a model of sepsis. We now propose to evaluate the effect of
PIP-2 on lung injury in 2 mouse models of ALI associated with infection. The first will be
the Klebsiella pneumoniae infection model (Sp.Aim 1); the 2nd model will be the cecal
ligation and puncture (Sp. Aim 2). PIP-2 will be administered at either 12 or 24 hrs after
the bacterial insult. We will evauate the effect of PIP on lung inflammation, disruption of
the blood-gas barrier,and oxidative injury. We also will determine the effect of PIP on
lung bacterial load as the NOX2 inhibitor may interfere with PMN bactericidal
mechanisms. We propose that PIP-2 will have clinical application for the prevention of
lung inflammation and tissue oxidative injury that are major contributors to the
pathogenesis of ALI. We plan a phase 2 STTR application to evaluate the effect of PIP
treatment on more complex models of acute lung injury in large animal models and to
determine possible toxicological effects of peptide administration.

## Key facts

- **NIH application ID:** 9908865
- **Project number:** 1R41HL145848-01A1
- **Recipient organization:** PEROXITECH, LLC
- **Principal Investigator:** SHELDON I FEINSTEIN
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $299,866
- **Award type:** 1
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908865

## Citation

> US National Institutes of Health, RePORTER application 9908865, Evaluation of a peptide that inhibits  the activation of NOX2 and the generation of reactive oxygen species in protection against acute lung injury (1R41HL145848-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9908865. Licensed CC0.

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