Faculty Collaboration Database

Role of glutathione in lung retention of 99mTc-hexamethylpropyleneamine oxime in two unique rat models of hyperoxic lung injury. J Appl Physiol (1985) 2012 Aug 15;113(4):658-65

Date

05/26/2012

Pubmed ID

22628374

Pubmed Central ID

PMC3424063

DOI

10.1152/japplphysiol.00441.2012

Scopus ID

2-s2.0-84865136200 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

Rat exposure to 60% oxygen (O(2)) for 7 days (hyper-60) or to >95% O(2) for 2 days followed by 24 h in room air (hyper-95R) confers susceptibility or tolerance, respectively, of the otherwise lethal effects of subsequent exposure to 100% O(2). The objective of this study was to determine if lung retention of the radiopharmaceutical agent technetium-labeled-hexamethylpropyleneamine oxime (HMPAO) is differentially altered in hyper-60 and hyper-95R rats. Tissue retention of HMPAO is dependent on intracellular content of the antioxidant GSH and mitochondrial function. HMPAO was injected intravenously in anesthetized rats, and planar images were acquired. We investigated the role of GSH in the lung retention of HMPAO by pretreating rats with the GSH-depleting agent diethyl maleate (DEM) prior to imaging. We also measured GSH content and activities of mitochondrial complexes I and IV in lung homogenate. The lung retention of HMPAO increased by ≈ 50% and ≈ 250% in hyper-60 and hyper-95R rats, respectively, compared with retention in rats exposed to room air (normoxic). DEM decreased retention in normoxic (≈ 26%) and hyper-95R (≈ 56%) rats compared with retention in the absence of DEM. GSH content increased by 19% and 40% in hyper-60 and hyper-95R lung homogenate compared with normoxic lung homogenate. Complex I activity decreased by ≈ 50% in hyper-60 and hyper-95R lung homogenate compared with activity in normoxic lung homogenate. However, complex IV activity was increased by 32% in hyper-95R lung homogenate only. Furthermore, we identified correlations between the GSH content in lung homogenate and the DEM-sensitive fraction of HMPAO retention and between the complex IV/complex I activity ratio and the DEM-insensitive fraction of HMPAO retention. These results suggest that an increase in the GSH-dependent component of the lung retention of HMPAO may be a marker of tolerance to sustained exposure to hyperoxia.

Author List

Audi SH, Roerig DL, Haworth ST, Clough AV

Authors

Said Audi PhD Professor in the Biomedical Engineering department at Marquette University
Anne Clough PhD Professor in the Mathematics, Statistics, and Computer Science department at Marquette University

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

Animals
Disease Models, Animal
Electron Transport Complex I
Electron Transport Complex IV
Glutathione
Hyperoxia
Injections, Intravenous
Lung
Lung Injury
Malates
Male
Mitochondria
Radionuclide Imaging
Radiopharmaceuticals
Rats
Rats, Sprague-Dawley
Technetium Tc 99m Exametazime