Lung mitochondrial dysfunction in pulmonary hypertension syndrome. II. Oxidative stress and inability to improve function with repeated additions of adenosine diphosphate

Department of Poultry Science, Center of Excellence for Poultry Science, University of Arkansas, Fayetteville 72701, USA.

The major objective of this study was to examine lung mitochondrial dysfunction and antioxidants in pulmonary hypertension syndrome (PHS) in broilers. Lung mitochondria were obtained from broilers fed diets containing 15 IU (control) and 100 IU dl-alpha-tocopherol acetate, i.e., vitamin E (VE)/kg with and without PHS; the four treatment groups were control, VE, PHS, and VE-PHS, respectively (Experiment 1), or from healthy broilers genetically selected or not selected for resistance to PHS (Experiment 2). Mitochondrial function was assessed with sequential additions of adenosine diphosphate (ADP) to mimic a repeated demand for energy. Compared to controls, PHS mitochondria in Experiment 1 exhibited mitochondrial dysfunction [lower respiratory control (RCR) and ADP:O ratios and an inability to improve function with repeated energy demand] and oxidative stress [lower alpha-tocopherol and reduced glutathione (GSH) and higher oxidized glutathione levels (GSSG)]. High dietary alpha-tocopherol had no effect on lung mitochondrial function in healthy broilers (VE vs. controls) but attenuated dysfunction in VE-PHS mitochondria. In Experiment 2, there were no differences in selected and nonselected mitochondrial function following a single addition of ADP, but nonselected mitochondria exhibited lower RCR and ADP:O values with repeated energy demand. Higher GSSG levels were also observed in nonselected lung. The results indicate that lung mitochondrial dysfunction present in broilers with PHS was associated with oxidative stress and may be attenuated by high dietary vitamin E. Furthermore, genetic resistance to PHS was associated with more efficient oxidative phosphorylation in lung mitochondria and an inherently lower degree of oxidative stress.

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