title: N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation.
abstract: Sepsis is a common cause of acute kidney injury (AKI) and acute lung injury. Oxidative stress plays as important role in such injury. The aim of this study was to evaluate the effects that the potent antioxidant N-acetylcysteine (NAC) has on renal and pulmonary function in rats with sepsis. Rats, treated or not with NAC (4.8 g/l in drinking water), underwent cecal ligation and puncture (CLP) 2 days after the initiation of NAC treatment, which was maintained throughout the study. At 24 h post-CLP, renal and pulmonary function were studied in four groups: control, control + NAC, CLP, and CLP + NAC. All animals were submitted to low-tidal-volume mechanical ventilation. We evaluated respiratory mechanics, the sodium cotransporters Na-K-2Cl (NKCC1) and the α-subunit of the epithelial sodium channel (α-ENaC), polymorphonuclear neutrophils, the edema index, oxidative stress (plasma thiobarbituric acid reactive substances and lung tissue 8-isoprostane), and glomerular filtration rate. The CLP rats developed AKI, which was ameliorated in the CLP + NAC rats. Sepsis-induced alterations in respiratory mechanics were also ameliorated by NAC. Edema indexes were lower in the CLP + NAC group, as was the wet-to-dry lung weight ratio. In CLP + NAC rats, α-ENaC expression was upregulated, whereas that of NKCC1 was downregulated, although the difference was not significant. In the CLP + NAC group, oxidative stress was significantly lower and survival rates were significantly higher than in the CLP group. The protective effects of NAC (against kidney and lung injury) are likely attributable to the decrease in oxidative stress, suggesting that NAC can be useful in the treatment of sepsis.
authors.affiliation: Laboratory for Medical Research, Nephrology Department, University of SãoPaulo School of Medicine, São Paulo, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Campos
authors.forename: Maria Heloísa Massola
authors.initials: MH
authors.lastname: Shimizu
authors.forename: Rildo Aparecido
authors.initials: RA
authors.lastname: Volpini
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Bragança
authors.forename: Lucia
authors.initials: L
authors.lastname: Andrade
authors.forename: Fernanda Degobbi Tenório Quirino Dos Santos
authors.initials: FD
authors.lastname: Lopes
authors.forename: Clarice
authors.initials: C
authors.lastname: Olivo
authors.forename: Daniele
authors.initials: D
authors.lastname: Canale
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Seguro
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D058186:Acute Kidney Injury / Q000188:drug therapy / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002432:Cecum / Q000293:injuries; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D011654:Pulmonary Edema / Q000188:drug therapy / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial; D018805:Sepsis / Q000473:pathology* / Q000503:physiopathology; D015222:Sodium Channels / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2
chemical_list: D000975:Antioxidants; C578879:Slc12a2 protein, rat; D015222:Sodium Channels; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D000111:Acetylcysteine