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1
Revelli S, Le Page C, Piaggio E, Wietzerbin J, Bottasso O, 1999. Benznidazole, a drug employed in the treatment of Chagas’ disease, down-regulates the synthesis of nitrite and cytokines by murine stimulated macrophages. Clin Exp Immunol 118 :271–277.
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2
Piaggio E, Sanceau J, Revelli S, Bottasso O, Wietzerbin J, Serra E, 2001. Trypanocidal drug benznidazole impairs lipopolysaccharide induction of macrophage nitric oxide synthase gene transcription through inhibition of NF-kappa B activation. J Immunol 167 :3422–3426.
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3
Piaggio E, Roggero E, Pitashny M, Wietzerbin J, Bottasso O, Revelli S, 2001. Treatment with benznidazole and its immuno-modulating effects on Trypanosoma cruzi-infected rats. Parasitol Res 87 :539–547.
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4
Pascutti MF, Pitashny M, Nocito A, Guermonprez P, Amigorena S, Wietzerbin J, Serra E, Bottasso O, Revelli S, 2004. Benznidazole, a drug used in Chagas’ disease, ameliorates LPS-induced inflammatory response in mice. Life Sci 76 :685–697.
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5
Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ, 1992. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101 :1644–1655.
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6
Vassalli P, 1992. The pathophysiology of tumor necrosis factors. Annu Rev Immuno l10 :411–452.
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7
Wichterman KA, Baue AE, Chaudry IH, 1980. Sepsis and septic shock a review of laboratory models and a proposal. J Surg Res 29 :189–201.
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8
Deitch EA, 1998. Animal models of sepsis and shock: a review and lessons learned. Shock 9 :1–11.
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9
Chung CS, Watkins L, Funches A, Lomas-Neira J, Cioffi WG, Ayala A, 2006. Deficiency of γ δ T lymphocytes contributes to mortality and immunosuppression in sepsis. Am J Physiol Regul Integr Comp Physiol 291 :R1338–R1343.
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10
Gallos G, Jones DR, Nasr SH, Emala CW, Lee HT, 2004. Local anesthetics reduce mortality and Project against renal and hepatic dysfunction in murine septic peritonitis. Anesthesiology 101 :902–911.
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11
Baker CC, Chaudry JH, Gaines HO, 1983. Evaluation of factors affecting mortality rate alter sepsis in a murine cecal ligation and puncture model. Surgery 94 :331–335.
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12
Casey LC, Balk RA, Bon RC, 1993. Plasma cytokine and endotoxin levels correlate with survival in patients with sepsis syndrome. Ann Intern Med 119 :771–778.
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13
Rodriguez Coura J, De Castro SL, 2002. A critical review on Chagas disease chemotherapy. Mem Inst Oswaldo Cruz 97 :3–24.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 103 | 70 | 4 |
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Beneficial Effects of Benznidazole during an Infectious-based Situation of Systemic Inflammatory Response: Cecal Ligation and Puncture
Romina Manarin
Romina Manarin
Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina; Instituto de Biología Molecular y Celular de Rosario (IBR)-CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina
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Emanuel Bottasso
Emanuel Bottasso
Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina; Instituto de Biología Molecular y Celular de Rosario (IBR)-CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina
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Oscar Bottasso
Oscar Bottasso
Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina; Instituto de Biología Molecular y Celular de Rosario (IBR)-CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina
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Esteban Serra
Esteban Serra
Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina; Instituto de Biología Molecular y Celular de Rosario (IBR)-CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina
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Silvia Revelli
Silvia Revelli
Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina; Instituto de Biología Molecular y Celular de Rosario (IBR)-CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina
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We have shown that benznidazole (BZL), a drug used to treat Chagas disease, markedly reduced the production of pro-inflammatory cytokines and NO-derived metabolites in experimentally Trypanosoma cruzi–infected rats. Treatment with BZL exerted beneficial effects in a model of inflammation-based pathology like murine experimental endotoxemia. Based on these findings, we wished to ascertain the effect of BZL in a closer situation to sepsis: the cecal ligation and puncture (CLP) model in C57BL/6 mice. We analyzed clinical course, survival, circulating levels of inflammation-related compounds (NO, tumor necrosis factor [TNF]-α), and bacteriemia. Recipients of BZL, 25 mg/kg, had an increased survival rate at 24 hours after CLP, showing a better clinical situation and a significant reduction of TNF-α levels and bacteriemia, with respect to the other groups. BZL failed to inhibit in vitro bacterial growth, suggesting that these effects may be partly caused by the immunomodulatory effects of BZL.
Author Notes
ProCite
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-
1
Revelli S, Le Page C, Piaggio E, Wietzerbin J, Bottasso O, 1999. Benznidazole, a drug employed in the treatment of Chagas’ disease, down-regulates the synthesis of nitrite and cytokines by murine stimulated macrophages. Clin Exp Immunol 118 :271–277.
-
2
Piaggio E, Sanceau J, Revelli S, Bottasso O, Wietzerbin J, Serra E, 2001. Trypanocidal drug benznidazole impairs lipopolysaccharide induction of macrophage nitric oxide synthase gene transcription through inhibition of NF-kappa B activation. J Immunol 167 :3422–3426.
-
3
Piaggio E, Roggero E, Pitashny M, Wietzerbin J, Bottasso O, Revelli S, 2001. Treatment with benznidazole and its immuno-modulating effects on Trypanosoma cruzi-infected rats. Parasitol Res 87 :539–547.
-
4
Pascutti MF, Pitashny M, Nocito A, Guermonprez P, Amigorena S, Wietzerbin J, Serra E, Bottasso O, Revelli S, 2004. Benznidazole, a drug used in Chagas’ disease, ameliorates LPS-induced inflammatory response in mice. Life Sci 76 :685–697.
-
5
Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ, 1992. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101 :1644–1655.
-
6
Vassalli P, 1992. The pathophysiology of tumor necrosis factors. Annu Rev Immuno l10 :411–452.
-
7
Wichterman KA, Baue AE, Chaudry IH, 1980. Sepsis and septic shock a review of laboratory models and a proposal. J Surg Res 29 :189–201.
-
8
Deitch EA, 1998. Animal models of sepsis and shock: a review and lessons learned. Shock 9 :1–11.
-
9
Chung CS, Watkins L, Funches A, Lomas-Neira J, Cioffi WG, Ayala A, 2006. Deficiency of γ δ T lymphocytes contributes to mortality and immunosuppression in sepsis. Am J Physiol Regul Integr Comp Physiol 291 :R1338–R1343.
-
10
Gallos G, Jones DR, Nasr SH, Emala CW, Lee HT, 2004. Local anesthetics reduce mortality and Project against renal and hepatic dysfunction in murine septic peritonitis. Anesthesiology 101 :902–911.
-
11
Baker CC, Chaudry JH, Gaines HO, 1983. Evaluation of factors affecting mortality rate alter sepsis in a murine cecal ligation and puncture model. Surgery 94 :331–335.
-
12
Casey LC, Balk RA, Bon RC, 1993. Plasma cytokine and endotoxin levels correlate with survival in patients with sepsis syndrome. Ann Intern Med 119 :771–778.
-
13
Rodriguez Coura J, De Castro SL, 2002. A critical review on Chagas disease chemotherapy. Mem Inst Oswaldo Cruz 97 :3–24.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 103 | 70 | 4 |
| Full Text Views | 207 | 2 | 0 |
| PDF Downloads | 46 | 2 | 0 |