title: Platonin mitigates lung injury in a two-hit model of hemorrhage/resuscitation and endotoxemia in rats.
abstract: BACKGROUND
  Traumatic hemorrhagic shock and subsequent resuscitation may promote bacteria translocation and cause endotoxemia, a two-hit process that will induce severe lung injury. The pathogenesis involves oxidative stress, neutrophil infiltration, and inflammatory response. Platonin, a potent antioxidant, possesses potent anti-inflammation capacity. We sought to elucidate whether platonin could mitigate acute lung injury in a two-hit model of traumatic hemorrhage/resuscitation and subsequent endotoxemia.
  
  
  METHODS
  Adult male rats were randomized to receive traumatic hemorrhage/resuscitation plus lipopolysaccharide (HS/L) alone or HS/L plus platonin (200 μg/kg; n = 12 in each group). Sham groups were used simultaneously. At 6 hours after resuscitation, rats were killed and the levels of lung injury were assayed.
  
  
  RESULTS
  Rats treated with HS/L alone had severe lung injury as evidenced by significant alterations in lung function (i.e., arterial blood gas and alveolar-arterial oxygen difference) and histology. Significant increases in polymorphonuclear leukocytes/alveoli ratio (neutrophil infiltration index) and significant increases in the concentrations of inflammatory molecules (including chemokine, cytokine, and prostaglandin E2) and malondialdehyde (lipid peroxidation index) revealed that HS/L caused significant oxidative stress, neutrophil infiltration, and inflammatory response in rat lungs. Moreover, our data revealed that the levels of functional and histologic alteration as well as polymorphonuclear leukocytes/alveoli ratio and the concentrations of inflammatory molecules and malondialdehyde in rats treated with HS/L plus platonin (200 μg/kg) were significantly lower than those treated with HR/L alone.
  
  
  CONCLUSIONS
  Platonin mitigates lung injury in a two-hit model of traumatic hemorrhage/resuscitation and endotoxemia in rats.
authors.affiliation: Department of Anesthesiology, China Medical University Hospital & College of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Kuen-Bao
authors.initials: KB
authors.lastname: Chen
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Lee
authors.forename: Jie-Jen
authors.initials: JJ
authors.lastname: Lee
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Tsai
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Huang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D013844:Thiazoles / Q000633:toxicity*
chemical_list: D013844:Thiazoles; C032149:platonin