Beneficial effects of benznidazole during an infectious-based situation of systemic inflammatory response: cecal ligation and puncture.
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]-alpha), 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-alpha 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.
Manarin
Romina
R
Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina. r.manarin@yahoo.com.ar
Bottasso
Emanuel
E
Bottasso
Oscar
O
Serra
Esteban
E
Revelli
Silvia
S
D000818:Animals; D016470:Bacteremia / Q000188:drug therapy; D014355:Chagas Disease / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009593:Nitroimidazoles / Q000627:therapeutic use*; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D014409:Tumor Necrosis Factor-alpha; C009999:benzonidazole