Benznidazole, a drug used in Chagas' disease, ameliorates LPS-induced inflammatory response in mice

被引:24
作者
Pascutti, MF
Pitashny, M
Nocito, AL
Guermonprez, P
Amigorena, S
Wietzerbin, J
Serra, E
Bottasso, O
Revelli, S
机构
[1] Fac Ciencias Med, Inst Inmunol, RA-2000 Rosario, Santa Fe, Argentina
[2] Univ Nacl Rosario, Fac Ciencias Med, Catedra Anat Patol, RA-2000 Rosario, Argentina
[3] Inst Curie, INSERM, U520, Paris, France
[4] Inst Curie, INSERM, U365, Paris, France
[5] Consejo Nacl Invest Cient & Tecn, Inst Biol Celular & Mol Rosario, Rosario, Argentina
关键词
benznidazole; inducible nitric oxide synthase; cytokines; experimental endotoxemia;
D O I
10.1016/j.lfs.2004.09.013
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Benznidazole (BZL) is a drug currently used for treating Chagas' disease. Given our earlier demonstration in which BZL downregulated cytokine and nitric oxide (NO) synthesis by LPS and/or IFN-gamma-stimulated murine macrophages, we have now analysed whether this compound could exert beneficial effects in a model of LPS-induced inflammation in C57BL/6 mice. The lethal model consisted of two LPS intraperitoneal injections, 200 mug each separated by 2 h, with BZL given orally at a dose of 200 mg/kg, 18 and 2 h before the first challenge and 20 and 44 hr following the second one. In this model, BZL treatment led to a significantly decreased mortality in comparison with untreated counterparts. Remaining experiments were carried out in mice given a unique LPS dose, pretreated with BZL or not, since those subjected to the lethal protocol were unsuitable for laboratory handling. Analysis of IL-1beta, IL-6, TNF-alpha, IL-12 and NOS mRNA expression in liver samples taken at 90 min post-LPS showed a marked reduction of the two latter mRNAs in BZL-treated mice. These animals also displayed significantly decreased peaks levels of serum TNF-alpha and IL-6, accompanied by a diminished number of IL-6-producing peritoneal macrophages. Present effects may broaden the potential usefulness of BZL in situations accompanied by an excessive inflammatory response. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:685 / 697
页数:13
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