Mitochondrial reactive oxygen species production in lungs of rats with different susceptibilities to hyperoxia-induced acute lung injury.

Adult rats exposed to hyperoxia (>95 % O) die within 60-72 h from respiratory failure. However, when preconditioned with either >95 % O for 48 h followed by 24 h in room air (H-T) or 60 % O for 7 days (H-S), they acquire tolerance or susceptibility to hyperoxia, respectively. The aim was to quantify HO 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 HO 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 HO scavenging systems. Lung rate of HO release was quantified in IPLs with and without CII inhibitor. Results from isolated mitochondria show that CII is the main HO source, and that both HO 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 HO source from lung tissue, and that HO 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 HO production and scavenging capacity were significantly lower than those in normoxia mitochondria and may contribute to their increased hyperoxia susceptibility. The lower HO release rate from H-T IPLs, along with no change in mitochondrial HO production rate, is consistent with higher antioxidant capacity in the lungs of H-T rats, which may contribute to their hyperoxia tolerance.