title: Benznidazole, a drug used in Chagas' disease, ameliorates LPS-induced inflammatory response in mice.
abstract: 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 microg 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 iNOS 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.
authors.affiliation: Instituto de Inmunología, Facultad de Ciencias Médicas, Santa Fe 3100, 2000, Rosario, Argentina.
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: Pascutti
authors.forename: Milena
authors.initials: M
authors.lastname: Pitashny
authors.forename: Ana Lía
authors.initials: AL
authors.lastname: Nocito
authors.forename: Pierre
authors.initials: P
authors.lastname: Guermonprez
authors.forename: Sebastian
authors.initials: S
authors.lastname: Amigorena
authors.forename: Juana
authors.initials: J
authors.lastname: Wietzerbin
authors.forename: Esteban
authors.initials: E
authors.lastname: Serra
authors.forename: Oscar
authors.initials: O
authors.lastname: Bottasso
authors.forename: Silvia
authors.initials: S
authors.lastname: Revelli
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014355:Chagas Disease / Q000188:drug therapy*; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000188:drug therapy; D005434:Flow Cytometry; D007249:Inflammation / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009593:Nitroimidazoles / Q000627:therapeutic use*; D010533:Peritoneal Lavage; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017931:DNA Primers; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C009999:benzonidazole