Peroxiredoxin 6 gene-targeted mice show increased lung injury with paraquat-induced oxidative stress.
Mice with knock-out of peroxiredoxin 6 (Prdx6), a recently described antioxidant enzyme, were evaluated for susceptibility to lung injury with paraquat (PQ) administration. With high dose PQ (30 mg/kg i.p.), all Prdx6-/- mice died (LT50 54 +/- 2.05 h, mean +/- SE) by 4 days, whereas 86% of the wild-type (WT) mice (C57BL/6) survived (n = 14). At 2 days after PQ, lung wet/dry weight ratio increased significantly (p < 0.05) to 7.57 +/- 0.37 in Prdx6-/- mice vs. 5.42 +/- 0.25 in WT mice. Total protein and nucleated cells in bronchoalveolar lavage fluid and TBARS and protein carbonyls in lung homogenate also showed more marked increases in Prdx6-/- mice. At 2.5 days after PQ, light microscopy of WT lungs showed mild injury while Prdx6-/- lungs showed epithelial cell necrosis, perivascular edema, and inflammatory cells. With low dose PQ (12.5 mg/kg), mortality and lung injury were less marked but were significantly greater with Prdx6-/- compared to WT mice. These results show that Prdx6-/- mice have increased susceptibility to lung injury with PQ administration. Thus, Prdx6 protects lungs against PQ toxicity as shown previously for hyperoxia, indicating that it functions as an important lung antioxidant enzyme.
Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-6068, USA.
Yan
Y
Wang
Sheldon I
SI
Feinstein
Yefim
Y
Manevich
Ye-Shih
YS
Ho
Aron B
AB
Fisher
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D008168:Lung / Q000187:drug effects / Q000473:pathology; D055370:Lung Injury; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000633:toxicity*; D010544:Peroxidases / Q000172:deficiency / Q000235:genetics*; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D017392:Thiobarbituric Acid Reactive Substances; D010544:Peroxidases; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; C515983:Prdx6 protein, mouse; D010269:Paraquat