title: Intratracheal co-administration of antioxidants and ceftriaxone reduces pulmonary injury and mortality rate in an experimental model of sepsis.
abstract: OBJECTIVE
  Recent studies showed that both sepsis and antibiotic therapy are associated with cell death and linked to reactive oxygen species generation. This study investigated the effects of intratracheal administration of combinations of antioxidants (n-acetyl cysteine (NAC), vitamins C and E) in the treatment of sepsis-induced lung injury.
  
  
  METHODS
  Ninety-six male Wistar rats subjected to sepsis were treated with ceftriaxone plus NAC with or without vitamins C and E and compared to appropriate controls. As an index of oxidative damage protein carbonyls, sulfhydryl groups, lipid peroxidation and superoxide anion were measured, as well as superoxide dismutase and catalase. Histopathological alterations and mortality rate were also analyzed.
  
  
  RESULTS
  Twenty-four hours after sepsis induction, markers of oxidative stress increased in all lungs examined. Ceftriaxone plus intratracheal combination of NAC, vitamins C and E decreased lung injury in infected animals by reducing superoxide anion production (54%), lipid peroxidation (53%) and protein carbonyl (58%) and restored the redox status (7.5 times). This therapy also reduced the imbalance of antioxidant enzymes activities and attenuated the alveolar architectural disorganization, inflammatory cell infiltration and pulmonary oedema. Survival increased from 66.6% with ceftriaxone to 83.2% with ceftriaxone plus antioxidants.
  
  
  CONCLUSIONS
  Ceftriaxone plus intratracheal co-administration of antioxidants provides better protection, by decreasing pulmonary oxidative stress, limiting histophatological alterations and improving survival. Antioxidants should be explored as a co-adjuvant in the treatment of severe lung injury.
authors.affiliation: Department of Microbiology and Cell Culture, Laboratory of Immunopathology Keizo Asami-LIKA, Recife, Pernambuco.
authors.forename: Andre M
authors.initials: AM
authors.lastname: Galvão
authors.forename: Marcela S O
authors.initials: MS
authors.lastname: Wanderley
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Silva
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Filho
authors.forename: Mário R
authors.initials: MR
authors.lastname: Melo-Junior
authors.forename: Luciano A
authors.initials: LA
authors.lastname: Silva
authors.forename: Emílio L
authors.initials: EL
authors.lastname: Streck
authors.forename: Armele F
authors.initials: AF
authors.lastname: Dornelas de Andrade
authors.forename: Maria B
authors.initials: MB
authors.lastname: Souza Maia
authors.forename: Celia M M
authors.initials: CM
authors.lastname: Barbosa de Castro
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage; D002443:Ceftriaxone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004359:Drug Therapy, Combination; D055370:Lung Injury / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000150:complications / Q000188:drug therapy*; D014132:Trachea; D014810:Vitamin E / Q000008:administration & dosage
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D014810:Vitamin E; D002443:Ceftriaxone; D001205:Ascorbic Acid; D000111:Acetylcysteine
keywords: acute lung injury; antioxidant; ceftriaxone; oxidative stress; sepsis