title: Apocynin suppressed the nuclear factor-κB pathway and attenuated lung injury in a rat hemorrhagic shock model.
abstract: The aim of this study was to investigate whether a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) inhibitor, apocynin, reduces reactive oxygen species (ROS) production, suppresses the nuclear factor κB (NF-κB) pathway, attenuates lung injury, and improves survival in rat hemorrhagic shock (HS) model.
  
  
  
  Blood was drawn from male Sprague-Dawley rats (290-340 g) to maintain a mean arterial pressure of 20-25 mm Hg for 40 minutes. The rats were resuscitated with the drawn blood, and a vehicle (HS), a low dose of apocynin (20 mg/kg, LD-Apo), or a high dose of apocynin (40 mg/kg, HD-Apo) was administered intraperitoneally. The survival of the rats was observed for 72 hours. Then, a separated set of rats was euthanized at 6 hours post-HS induction. We measured gp91-phox (Nox2) expression, Nox activity, cytoplasmic phosphorylated inhibitor κB-α (p-IκB-α) expression, NF-κB p65 DNA-binding activity, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) gene expressions, malondialdehyde (MDA) level, myeloperoxidase (MPO) activity, and histological damage in the lung tissues.
  
  
  
  The survival rates of the sham, HS, HS + LD-Apo, and HS + HD-Apo groups were 100% (5/5), 30% (3/10), 40% (4/10), and 70% (7/10), respectively. A high dose of apocynin decreased gp91-phox expression, Nox activity, and MDA level in the lung tissues during HS and resuscitation. It also decreased p-IκB-α expression, NF-κB p65 DNA-binding activity, TNF-α and IL-6 gene expressions, and MPO activity in the lung tissues and attenuated histological lung injuries. However, a low dose of apocynin failed to show these benefits.
  
  
  
  The administration of a high dose of apocynin inhibited Nox2 expression and Nox activity, reduced lipid peroxidation, suppressed the NF-κB pathway and subsequent pro-inflammatory cytokines transcription in the lung tissues, and attenuated lung injury during HS and resuscitation in rats.
authors.affiliation: From the Trauma Center (S.H.C.), Dankook University Hospital, Cheonan-si, Chungnam, Republic of Korea; and Department of Emergency Medicine (G.J.S., W.Y.K., K.S.K., M.J.P., T.K., J.I.K.), Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Seok Ho
authors.initials: SH
authors.lastname: Choi
authors.forename: Gil Joon
authors.initials: GJ
authors.lastname: Suh
authors.forename: Woon Yong
authors.initials: WY
authors.lastname: Kwon
authors.forename: Kyung Su
authors.initials: KS
authors.lastname: Kim
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Park
authors.forename: Taegyun
authors.initials: T
authors.lastname: Kim
authors.forename: Jeong In
authors.initials: JI
authors.lastname: Ko
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D015227:Lipid Peroxidation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000378:metabolism; D015996:Survival Rate
chemical_list: D000098:Acetophenones; D015415:Biomarkers; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C056165:acetovanillone; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases