Faculty Collaboration Database

Mitochondrial reactive oxygen species production in lungs of rats with different susceptibilities to hyperoxia-induced acute lung injury. Biochim Biophys Acta Bioenerg 2025 Nov 01;1866(4):149561

Date

06/15/2025

Pubmed ID

40516644

Pubmed Central ID

PMC12354310

DOI

10.1016/j.bbabio.2025.149561

Scopus ID

2-s2.0-105008145920 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Adult rats exposed to hyperoxia (>95 % O₂) die within 60-72 h from respiratory failure. However, when preconditioned with either >95 % O₂ for 48 h followed by 24 h in room air (H-T) or 60 % O₂ for 7 days (H-S), they acquire tolerance or susceptibility to hyperoxia, respectively. The aim was to quantify H₂O₂ production rate and identify sources in isolated lung mitochondria and isolated perfused lungs (IPLs) of normoxia, H-T, and H-S rats. Mitochondria were isolated from lungs, and H₂O₂ production rates were quantified in the presence of pyruvate-malate or succinate, with and without inhibitors of mitochondrial complex I (CI), complex II (CII), and/or H₂O₂ scavenging systems. Lung rate of H₂O₂ release was quantified in IPLs with and without CII inhibitor. Results from isolated mitochondria show that CII is the main H₂O₂ source, and that both H₂O₂ production rate and scavenging capacity were ~48 % lower in H-S mitochondria compared to normoxia. Results from IPLs show that CII is also the dominant H₂O₂ source from lung tissue, and that H₂O₂ release rate was lower in H-T lungs compared to normoxia and H-S lungs. These results suggest that for H-S rats, both mitochondrial rate of H₂O₂ production and scavenging capacity were significantly lower than those in normoxia mitochondria and may contribute to their increased hyperoxia susceptibility. The lower H₂O₂ release rate from H-T IPLs, along with no change in mitochondrial H₂O₂ production rate, is consistent with higher antioxidant capacity in the lungs of H-T rats, which may contribute to their hyperoxia tolerance.

Author List

Taheri P, Dave DD, Taye A, Clough AV, Jacobs ER, Dash RK, Audi SH

Authors

Said Audi PhD Professor in the Biomedical Engineering department at Marquette University
Ranjan K. Dash PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin
Devanshi D. Dave Postdoctoral Researcher 4 in the Biomedical Engineering department at Medical College of Wisconsin
Elizabeth R. Jacobs MD Emeritus Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Lung Injury
Animals
Electron Transport Complex I
Electron Transport Complex II
Hydrogen Peroxide
Lung
Malates
Male
Mitochondria
Oxygen
Pyruvates
Rats
Rats, Sprague-Dawley
Succinic Acid