Benznidazole, a drug used in Chagas' disease, ameliorates LPS-induced inflammatory response in mice.
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.
Pascutti
María Fernanda
MF
Instituto de Inmunología, Facultad de Ciencias Médicas, Santa Fe 3100, 2000, Rosario, Argentina.
Pitashny
Milena
M
Nocito
Ana Lía
AL
Guermonprez
Pierre
P
Amigorena
Sebastian
S
Wietzerbin
Juana
J
Serra
Esteban
E
Bottasso
Oscar
O
Revelli
Silvia
S
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
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