The effects of hydrogen-peroxide (7722841) (H2O2) on alveolar type- II cells were examined. Alveolar type-II cells were isolated from the lungs of male Sprague-Dawley-rats and evaluated in the presence or absence of 0.05 to 0.5 millimolar (mM) H2O2. No changes in membrane integrity and mean cell volume, as determined by the exclusion of trypan-blue dye, could be detected as a result of H2O2 exposure. A dose dependent decrease in intracellular ATP levels and oxygen consumption was seen after H2O2 incubation. Isolated mitochondria demonstrated a dose dependent inhibition of ATP synthesis in the presence of H2O2, with a decrease of about 50% seen at a concentration of 0.5mM H2O2. In the presence of succinate and ADP, mitochondrial oxygen consumption was reduced in a concentration dependent manner with H2O2; however, no effect was noted with succinate alone. The addition of carbonyl-cyanide-m- chlorophenylhydrazone to H2O2 or untreated mitochondria resulted in an increase in oxygen consumption in the presence of succinate. The decrease in ATP levels seen after a 1 hour incubation with 0.1mM H2O2 was partially reversible after 3 hours. The rate of disappearance of H2O2 from the culture medium was dependent upon the concentration and cell number. An inhibition in the association of 3-o-methylglucose with cells was seen after a 10 minute exposure to approximately 35%. The authors conclude that H2O2 affects cellular respiration by damaging mitochondria, interfering in the phosphorylation of ADP to ATP, and inhibiting glucose uptake and glycolysis.
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