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Inflammation
Published in: Inflammation 6/2011

01-12-2011

Effect of N-Acetylcysteine and Fructose-1,6-Bisphosphate in the Treatment of Experimental Sepsis

Authors: Ricardo Obalski de Mello, Adroaldo Lunardelli, Eduardo Caberlon, Cristina Machado Bragança de Moraes, Roberto Christ Vianna Santos, Vinicius Lorini da Costa, Gabriela Viegas da Silva, Patrícia da Silva Scherer, Luiz Eduardo Coimbra Buaes, Denizar Alberto da Silva Melo, Márcio Vinícius Fagundes Donadio, Fernanda Bordignon Nunes, Jarbas Rodrigues de Oliveira

Published in: Inflammation | Issue 6/2011

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Abstract

Sepsis is a syndrome caused by uncontrolled systemic inflammatory response of the individual, which represents a serious epidemiological problem worldwide. The aim of this study was to investigate the effect of N-acetylcysteine (NAC) and fructose-1,6-bisphosphate (FBP) in the treatment of experimental sepsis. We used rats that were divided into five experimental groups: normal control (not induced), septic control (induced using a capsule with non sterile fecal content and Escherichia coli), treated with FBP (500 mg/kg i.p.), treated with NAC (150 mg/kg i.p.), and treated with the combination of FBP with NAC. In the group treated with NAC, 16.68% of the mice survived, the FBP reduced the mortality of mice during the acute stage of the disease and increased the animals’ survival time in 33.34%, and the combination of drugs had no effect. Our results show that NAC prevented the mortality of animals after septic induction. These data confirm the validity of the use of NAC in the treatment of sepsis. Our data also show that the synergistic action with FBP does not improve the picture.
Literature
1.
Bone, R.C. 1991. The pathogenesis of sepsis. Annals of Internal Medicine 115: 457–469.PubMed
2.
3.
Bochud, P.Y., and T. Calandra. 2003. Pathogenesis of sepsis: new concepts and implications for future treatment. BMJ 326: 262–266.PubMedCrossRef
4.
Martin, G.S., D.M. Mannino, S. Eaton, et al. 2003. Epidemiology of sepsis in the United States from 1979 through 2000. The New England Journal of Medicine 348: 1546–1554.PubMedCrossRef
5.
Silva, E., A. Pedro Mde, A.C. Sogayar, T. Mohovic, C.L. Silva, M. Janiszewski, R.G. Cal, E.F. Sousa, T.P. Abe, J. Andrade, J.D. Matos, E. Rezende, M. Assunção, A. Avezum, P.C. Rocha, G.F. Matos, A.M. Bento, A.D. Corrêa, P.C. Vieira, and E. Knobel. 2004. Brazilian Sepsis Epidemiological Study. Critical Care 8(4): 251–260.CrossRef
6.
Hinshaw, L.B. 1996. Sepsis/Septic shock: participation of the microcirculation: Na abbreviated review. Critical Care Medicine 24: 1072–1078.PubMedCrossRef
7.
Creteur, J., and J.L. Vicente. 2000. Hemoglobin solutions: an “all-in-one” therapeutic strategy in sepsis? Critical Care Medicine 28: 894–896.PubMedCrossRef
8.
Thijs, L.G., et al. 1995. Time course of citokine levels in sepsis. Intensive Care Medicine 21: S258–S263.PubMedCrossRef
9.
Davies, M.G., and P.O. Hagen. 1997. Systemic inflammatory response syndrome. The British Journal of Surgery 84(7): 920–935.PubMedCrossRef
10.
Rubanyi, G.M. 1996. Fatores derivados do endotélio no choque. Clin Bras Med Intensiva 3: 13–26.
11.
Groeneveld, A.B.C., A.D.M. Kester, and J.J.P. Nauta. 1987. Relation of arterial blood lactate to oxygen delivery and hemodynamic variables in human shock states. Circulatory Shock 22: 35–53.PubMed
12.
Metrangolo, L., M. Fiorillo, G. Friedman, et al. 1995. Early hemodynamic course of septic shock. Critical Care Medicine 23: 1931–1975.CrossRef
13.
Benjamin, E., A.B. Leibowitz, J. Oropello, and T.J. Iberti. 1992. Systemic hypoxic and inflammatory syndrome: an alternative designation for “sepsis syndrome”. Critical Care Medicine 20: 680–682.PubMedCrossRef
14.
Azevedo, L.C., M. Janiszewski, F.G. Sorino, and F.R. Laurino. 2006. Redox mechanisms of vascular cell dysfunction in sepsis. Endocrine, Metabolic & Immune Disorders Drug Targets 6: 159–164.
15.
Halliwell, B., and J.M.C. Gutteridge. 1999. Free radicals in biology and medicine, 3rd ed. New York: Oxford University Press.
16.
Dalle-Donne, I., G. Aldini, M. Carini, R. Colombo, R. Rossi, and A. Milzani. 2006. Protein carbonylation, cellular dysfunction and disease progression. Journal of Cellular and Molecular Medicine 10(2): 389–406.PubMedCrossRef
17.
Carvalho, P.R.A., and E.A. Trotta. 2003. Avanços no diagnóstico e tratamento da sepse. Jornal de Pediatria 79(2): S195–S204.PubMedCrossRef
18.
Aiub, C.A.F., R. Bortolini, and A.A. Azambuja. 2003. Alves Filho JCF, Nunes FB, Oliveira JR. Alterations in the indexes of apoptosis and necrosis induced by galactosamine in the liver of Wistar rats treated with fructose-1, 6-bisphosphate. Hepatology Research 25(1): 83–91.CrossRef
19.
Oliveira, J.R., J.L. Rosa, S. Ambrosio, et al. 1992. Effect of galactosamine on hepatic carbohydrate metabolism: protective role of fructose-1, 6-bisphosphate. Hepatology 15: 1147–1153.PubMedCrossRef
20.
Nunes, F.B., and C.M. Graziottin. 2003. Alves Filho JCF, Lunardelli A, Pires MGS, Wächter PH, Oliveira JR. An assessment of fructose-1, 6-bisphosphate as an antimicrobial and anti-inflammatory agent in sepsis. Pharmacological Research 47(1): 35–41.PubMedCrossRef
21.
Cattani, L., R. Costrini, C. Cerilli, M.P. Rigobello, M. Bianchi, and L. Galzigna. 1980. Fructose-1, 6-diphosphate dependence on the toxicity and uptake of potassium ions. Agressologie 21: 263–264.PubMed
22.
Sola, A., J. Panes, C. Xaus, and G. Hotter. 2003. Fructose-1, 6-biphosphate and nucleoside pool modifications prevent neutrophil accumulation in the reperfused intestine. Journal of Leukocyte Biology 73: 74–81.PubMedCrossRef
23.
Nunes, F.B., C.M. Graziottin, J.C.F. Alves-Filho, A. Lunardelli, E. Caberlon, A. Peres, and J.R. Rodrigues. 2003. Immunomodulatory effect of fructose-1, 6-bisphosphate on T-lymphocytes. International Immunopharmacology 3: 267–272.CrossRef
24.
Nunes, F.B., and M.G.S. Pires. 2002. Alves Filho JCF, Wachter PH, Oliveira JR. Physiopathological studies in septic rats and the use of fructose-1, 6-bisphosphate as cellular protection. Critical Care Medicine 30: 2069–2074.PubMedCrossRef
25.
Pinho, R.A., P.C.L. Silveira, L.A. Silva, E.L. Streck, F. Dal-Pizzol, and J.C.F. Moreira. 2005. N-acetycysteine and deferoxamine reduce pulmonary oxidative stress and inflammation in rats after coal dust exposure. Environmental Research 99: 355–360.PubMedCrossRef
26.
Reed, D.J., and M.W. Fariss. 1984. Glutathione depletion and susceptibility. Pharmacological Reviews 36: 25S–33S.PubMed
27.
Heyman, S.N., M. Goldfarb, A. Shina, F. Karmeli, and S. Rosen. 2003. N-acetylcysteine ameliorates renal microcirculation: studies in rats. Kidney International 63(2): 634–641.PubMedCrossRef
28.
Prescott, L.F., R.N. Illingworth, J.A. Critchley, M.J. Stewart, R.D. Adam, and A.T. Proudfoot. 1979. Intravenous n-acetylcysteine: the treatment of choice for paracetamol poisoning. British Medical Journal 2: 1097–1100.PubMedCrossRef
29.
Miquel, J., M.L. Ferrandiz, E. De Juan, I. Sevila, and M. Martinez. 1995. N-acetylcysteine protects against age-related decline of oxidative phosphorylation in liver mitochondria. European Journal of Pharmacology 292: 333–335.PubMed
30.
Ritter, C., M.E. Andrades, A. Reinke, S. Menna-Barreto, J.C. Moreira, and F. Dal-Pizzol. 2004. Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis. Critical Care Medicine 32: 342–349.PubMedCrossRef
31.
Nunes, F.B., J.R. Oliveira, M.G.S. Pires, and P.H. Wächter. 2000. Septic induction in rats (Wistar): experimental model. Revista de Medicina da PUCRS 10: 183–187.
32.
Buege, J.A., and S.D. Aust. 1978. Microsomal Lipid Peroxidation. Methods Enzymology 52: 302–310.CrossRef
33.
Boveris, A., C.G. Fraga, A.I. Varsavsks, and O.R. Koch. 1983. Archives of Biochemistry and Biophysics 227: 534–541.PubMedCrossRef
34.
35.
Faure, P., and J.L. Lafond. 1995. Measurement of sulphydryl and carbonyl groups as a possible indicator of protein oxidation. Analysis of free radicals in biological systems. Boston: Verlag.
36.
Vandijck, D., J.M. Decruyenaere, and S.I. Blot. 2006. The value of sepsis definitions in daily ICU-practice. Acta Clinica Belgica 61(5): 220–226.PubMed
37.
Rudiger, A., M. Stotz, and M. Singer. 2008. Cellular processes in sepsis. Swiss Medical Weekly 138: 629–634.PubMed
38.
Dunn, L.L., Y.S. Rahmanto, and D.R. Richardson. 2007. Iron uptake and metabolism in the new millennium. Trends in Cell Biology 17(2): 93–100.PubMedCrossRef
39.
Cooper, J.M., and A.H. Schapira. 2007. Friedreich’s ataxia: coenzyme Q10 andvitamin E therapy. Mitochondrion 7(Suppl1): S127–135.PubMedCrossRef
40.
Barichello, T., J.J. Fortunato, A.M. Vitali, G. Feier, A. Reinke, J.C. Moreira, J. Quevedo, and F. Dal-Pizzol. 2006. Oxidative variables in the rat brain after sepsis induced by cecal ligation and perforation. Critical Care Medicine 34: 886–889.PubMedCrossRef
41.
Burdman, E. 1997. Epidemiologia. In IRA, insuficiência renal aguda: fisiopatologia, clínica e tratamento, ed. N. Schor, M.A. Boim, and O.F.P. Santos. São Paulo: Sarvier.
42.
Salvemini, D., and S. Cuzzocrea. 2003. Therapeutic potential of superoxide dismutase mimetics as therapeutic agents in critical care medicine. Critical Care Medicine 31: S29–S38.PubMedCrossRef
43.
Thiemermann, C. 2003. Membrane-permeable radical scavengers (tempol) for shock, ischemia-reperfusion injury, and inflammation. Critical Care Medicine 31: S76–S84.PubMedCrossRef
44.
Sprong, R.C., A.M.L. Winkelhuyzen-Janssen, C.J.M. Aarsman, J.F. Oirschot, T. Bruggen, and B.S. Asbeck. 1998. Low-dose Nacetylcysteine protects rats against endotoxin-mediated oxidative stress, but high-dose increases mortality. American Journal of Respiratory and Critical Care Medicine 157: 1283–1293.PubMed
45.
Brown, G.C., and V. Borutaite. 2004. Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols. Biochimica et Biophysica Acta 1658: 44–49.PubMedCrossRef
46.
Levy, M.M., M.P. Fink, J.C. Marshall, E. Abraham, D. Angus, D. Cook, J. Cohen, S.M. Opal, J.L. Vincent, and G. Ramsay. 2003. SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Critical Care Medicine 31(4): 1250–1256.PubMedCrossRef
47.
Oliveira, L.M., M.G.S. Pires, A.B. Magrisso, T.P. Munhoz, R. Roesler, and J.R. Oliveira. 2009. Fructose-1, 6-bisphosphate inhibits in vitro and ex vivo platelet aggregation induced by ADP and ameliorates coagulation alterations in experimental sepsis in rats. Journal of Thrombosis and Thrombolysis 29: 387–394.PubMedCrossRef
48.
Andrade, S.C., C. Dezoti, C.A. Shibuya, M. Watanabe, and M.F.F. Vattimo. 2004. Insuficiência Renal Aguda Isquêmica: Efeitos Comparativos do Alopurinol e N-Acetilcisteína como antioxidantes. Jornal Brasileiro De Nefrologia 26(2): 69–75.
49.
Pereira-Filho, G., C. Ferreira, A. Schwengber, C. Marroni, C. Zettler, and N. Marroni. 2008. Role of N-acetylcysteine on fibrosis and oxidative stress in cirrhotic rats. Arquivos de Gastroenterologia 45(2): 156–162.PubMedCrossRef
50.
Power, H.M., H.V. Heese, D.W. Beatty, J. Hughes, and W.S. Dempster. 1991. Iron fortification of infant milk formula: the effect on iron status and immune function. Annals of Tropical Paediatrics 11: 57–66.PubMed
51.
Souza, R.L., and R.C.M. Succi. 1996. Oligoelementos e Infecção. Pediatria Moderna 31: 660–667.
52.
Kent, S., E.D. Weinberg, and P. Stuart-Macadam. 1994. The etiology of the anemia of chronic disease and infection. Journal of Clinical Epidemiology 47: 23–33.PubMedCrossRef
53.
Cançado, R.D., and C.S. Chiattone. 2002. Anemia de doença crônica. Revista Brasileira de Hematologia e Hemoterapia 4: 127–136.
54.
Beaumont, C., and S. Vailont. 2006. Iron homeostasis. In Disorders of iron homeostasis, erythrocytes, erythropoiesis, ed. C. Beaumont, P. Beris, Y. Beuzard, and C. Brugnara. Genova: Forum Service Editore.
55.
Garcia Branco, R., R.C. Tasker, P.C. Ramos Garcia, J.P. Piva, and L. Dias Xavier. 2007. Glycemic control and insulin therapy in sepsis and critical illness. Jornal de Pediatria 83(5): S128–136.PubMedCrossRef
56.
Bowler, R.P., M. Nicks, K. Tran, et al. 2004. Extracellular superoxide dismutase attenuates lipopolysaccharide-induced neutrophilic in-flammation. American Journal of Respiratory Cell and Molecular Biology 31: 432–439.PubMedCrossRef
57.
Bowler, R.P., and J.D. Crapo. 2002. Oxidative stress in airways: Is there a role for extracellular superoxide dismutase? American Journal of Respiratory and Critical Care Medicine 166: S38–S43.PubMedCrossRef
58.
Ritter, C., A.A. Cunha, I.C. Echer, M. Andrades, A. Reinke, N. Lucchiari, J. Rocha, E.L. Streck, S. Menna-Barreto, J.C.F. Moreira, and F. Dal-Pizzol. 2006. Effects of N-acetylcysteine plus deferoxamine in lipopolysaccharide-induced acute lung injury in the rat. Critical Care Medicine 34: 471–477.PubMedCrossRef
Metadata
Title
Effect of N-Acetylcysteine and Fructose-1,6-Bisphosphate in the Treatment of Experimental Sepsis
Authors
Ricardo Obalski de Mello
Adroaldo Lunardelli
Eduardo Caberlon
Cristina Machado Bragança de Moraes
Roberto Christ Vianna Santos
Vinicius Lorini da Costa
Gabriela Viegas da Silva
Patrícia da Silva Scherer
Luiz Eduardo Coimbra Buaes
Denizar Alberto da Silva Melo
Márcio Vinícius Fagundes Donadio
Fernanda Bordignon Nunes
Jarbas Rodrigues de Oliveira
Publication date
01-12-2011
Publisher
Springer US
Published in
Inflammation / Issue 6/2011
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-010-9261-9

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