OBJECTIVE: Oxidative stress plays an important role in the development of multiple organ failure and septic shock. Here we have evaluated the effects of a combination of antioxidants (N-acetylcysteine plus deferoxamine) in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). DESIGN: Prospective, randomized, controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Male Wistar rats, weighing 300-350 g. INTERVENTIONS: Rats subjected to CLP were treated with either N-acetylcysteine (20 mg/kg, 3 hrs, 6 hrs, 12 hrs, 18 hrs, and 24 hrs after CLP, subcutaneously) plus deferoxamine (20 mg/kg, 3 hrs and 24 hrs after CLP, subcutaneously) or vehicle with or without "basic support" (saline at 50 mL/kg immediately and 12 hrs after CLP plus ceftriaxone at 30 mg/kg and clindamycin 25 mg/kg every 6 hrs). MEASUREMENTS AND MAIN RESULTS: After 12 hrs, tissue myeloperoxidase (indicator of neutrophil infiltration), thiobarbituric acid reactive species (as a marker of oxidative stress), catalase and superoxide dismutase activities (antioxidant enzymes), and mitochondrial superoxide production (index of uncoupling of electron transfer chain) were measured in major organs involved in septic response. Rats treated with antioxidants had significantly lower myeloperoxidase activity and thiobarbituric acid reactive species formation in all organs studied. Mitochondrial superoxide production was significantly reduced by antioxidant treatment. Furthermore, antioxidants significantly improved the balance between catalase and superoxide dismutase activities. Survival in untreated septic rats was 10%. Survival increased to 40% with fluids and antibiotics. In rats treated only with N-acetylcysteine plus deferoxamine, survival was also significantly improved (47%) in a manner similar to basic support. Survival increased to 66% with basic support with N-acetylcysteine plus deferoxamine. CONCLUSIONS: Our data provide the first experimental demonstration that N-acetylcysteine plus deferoxamine reduces the consequences of septic shock induced by CLP in the rat, by decreasing oxidative stress and limiting neutrophil infiltration and mitochondrial dysfunction, thereby improving survival.
OBJECTIVE: Oxidative stress plays an important role in the development of multiple organ failure and septic shock. Here we have evaluated the effects of a combination of antioxidants (N-acetylcysteine plus deferoxamine) in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). DESIGN: Prospective, randomized, controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Male Wistar rats, weighing 300-350 g. INTERVENTIONS:Rats subjected to CLP were treated with either N-acetylcysteine (20 mg/kg, 3 hrs, 6 hrs, 12 hrs, 18 hrs, and 24 hrs after CLP, subcutaneously) plus deferoxamine (20 mg/kg, 3 hrs and 24 hrs after CLP, subcutaneously) or vehicle with or without "basic support" (saline at 50 mL/kg immediately and 12 hrs after CLP plus ceftriaxone at 30 mg/kg and clindamycin 25 mg/kg every 6 hrs). MEASUREMENTS AND MAIN RESULTS: After 12 hrs, tissue myeloperoxidase (indicator of neutrophil infiltration), thiobarbituric acid reactive species (as a marker of oxidative stress), catalase and superoxide dismutase activities (antioxidant enzymes), and mitochondrial superoxide production (index of uncoupling of electron transfer chain) were measured in major organs involved in septic response. Rats treated with antioxidants had significantly lower myeloperoxidase activity and thiobarbituric acid reactive species formation in all organs studied. Mitochondrial superoxide production was significantly reduced by antioxidant treatment. Furthermore, antioxidants significantly improved the balance between catalase and superoxide dismutase activities. Survival in untreated septic rats was 10%. Survival increased to 40% with fluids and antibiotics. In rats treated only with N-acetylcysteine plus deferoxamine, survival was also significantly improved (47%) in a manner similar to basic support. Survival increased to 66% with basic support with N-acetylcysteine plus deferoxamine. CONCLUSIONS: Our data provide the first experimental demonstration that N-acetylcysteine plus deferoxamine reduces the consequences of septic shock induced by CLP in the rat, by decreasing oxidative stress and limiting neutrophil infiltration and mitochondrial dysfunction, thereby improving survival.
Authors: Luis Henrique Rapucci Moraes; Roberta Constâncio Bollineli; Daniela Sayuri Mizobuti; Leonardo Dos Reis Silveira; Maria Julia Marques; Elaine Minatel Journal: Redox Rep Date: 2014-10-31 Impact factor: 4.412
Authors: Tatiana Barichello; Joelson C Lemos; Jaqueline S Generoso; Andreza L Cipriano; Graziele L Milioli; Danielle M Marcelino; Francieli Vuolo; Fabricia Petronilho; Felipe Dal-Pizzol; Márcia Carvalho Vilela; Antonio Lucio Teixeira Journal: Neurochem Res Date: 2011-06-03 Impact factor: 3.996
Authors: Tatiana Barichello; Ana Lucia B Santos; Geovana D Savi; Jaqueline S Generoso; Paola Otaran; Cleonice M Michelon; Amanda V Steckert; Francielle Mina; Clarissa M Comim; Felipe Dal-Pizzol; João Quevedo Journal: Metab Brain Dis Date: 2012-05-17 Impact factor: 3.584
Authors: Fernanda S Neves; Patrícia T Marques; Fernanda Barros-Aragão; José Bruno Nunes; Aline M Venancio; Danielle Cozachenco; Rudimar L Frozza; Giselle F Passos; Robson Costa; Jade de Oliveira; Daiane F Engel; Andreza F De Bem; Claudia F Benjamim; Fernanda G De Felice; Sergio T Ferreira; Julia R Clarke; Claudia P Figueiredo Journal: Mol Neurobiol Date: 2016-12-13 Impact factor: 5.590
Authors: Patricia A Reis; Clarissa M Comim; Fernanda Hermani; Bruno Silva; Tatiana Barichello; Aline C Portella; Flavia C A Gomes; Ive M Sab; Valber S Frutuoso; Marcus F Oliveira; Patricia T Bozza; Fernando A Bozza; Felipe Dal-Pizzol; Guy A Zimmerman; João Quevedo; Hugo C Castro-Faria-Neto Journal: PLoS Pathog Date: 2010-06-24 Impact factor: 6.823