Premium
Intratracheal co‐administration of antioxidants and ceftriaxone reduces pulmonary injury and mortality rate in an experimental model of sepsis
Author(s) -
Galvão Andre M.,
Wanderley Marcela S.O.,
Silva Roberto A.,
Filho Carlos A.M.,
MeloJunior Mário R.,
Silva Luciano A.,
Streck Emílio L.,
Dornelas de Andrade Armele F.,
Souza Maia Maria B.,
Barbosa de Castro Celia M.M.
Publication year - 2014
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/resp.12363
Subject(s) - medicine , oxidative stress , lipid peroxidation , superoxide dismutase , pharmacology , sepsis , ceftriaxone , catalase , reactive oxygen species , superoxide , lung , immunology , antibiotics , biochemistry , chemistry , enzyme
Abstract Background and 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 W istar 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.