Oxidative stress induced necroptosis activation is involved in the pathogenesis of hyperoxic acute lung injury

Biochem Biophys Res Commun. 2018 Jan 15;495(3):2178-2183. doi: 10.1016/j.bbrc.2017.12.100. Epub 2017 Dec 18.

Abstract

Necroptosis has been found to be involved in the pathogenesis of some lung diseases, but its role in hyperoxic acute lung injury (HALI) is still unclear. This study aimed to investigate contribution of necroptosis to the pathogenesis of HALI induced by hyperbaric hyperoxia exposure in a rat model. Rats were divided into control group, HALI group, Nec-1 (necroptosis inhibitor) group and edaravone group. Rats were exposed to pure oxygen at 250 kPa for 6 h to induce HALI. At 30 min before hyperoxia exposure, rats were intraperitoneally injected with Nec-1 or edaravone, and sacrificed at 24 h after hyperoxia exposure. Lung injury was evaluated by histology, lung water to dry ratio (W/D) and bronchoalveolar lavage fluid (BALF) biochemistry; the serum and plasma oxidative stress, expression of RIP1, RIP3 and MLKL, and interaction between RIP1 and RIP3 were determined. Results showed hyperoxia exposure significantly caused damage to lung and increased necroptotic cells and the expression of RIP1, RIP3 and MLKL. Edaravone pre-treatment not only inhibited the oxidative stress in HALI, but also reduced necroptotic cells, decreased the expression of RIP1, RIP3 and MLKL and improved lung pathology. Nec-1 pretreatment inhibited necroptosis and improved lung pathology, but had little influence on oxidative stress. This study suggests hyperoxia exposure induces oxidative stress may activate necroptosis, involving in the pathology of HALI, and strategies targeting necroptosis may become promising treatments for HALI.

Keywords: Hyperoxic acute lung injury; MLKL; Necroptosis; RIP1; RIP3; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Bronchopulmonary Dysplasia / metabolism*
  • Bronchopulmonary Dysplasia / pathology*
  • Male
  • Necrosis / metabolism
  • Necrosis / pathology
  • Oxidative Stress*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism*

Substances

  • Reactive Oxygen Species