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 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.