Effect of the host specific treatment in the phagocytosis of Trypanosoma cruzi blood forms by mouse peritoneal macrophages

Abstract

Single doses of drugs active against Trypanosoma cruzi (megazol, nifurtimox and benznidazole) induce a rapid clearance of the blood parasites in experimentally infected mice. Furthermore, the in vitro phagocytosis and intracellular destruction by mouse peritoneal macrophage of blood forms collected from the treated animals is strongly enhanced as compared with parasites from untreated controls. The uptake of the blood forms by macrophages is significantly higher with megazol than with benznidazole and nifurtimox, a finding that concurs with data showing that megazol is also the most active compound in the living host. The possibility that macrophages participate in a synergic effect between the host immune response and chemotherapeutic effect is discussed.

In Vitro and In Vivo Activities of 1,3,4-Thiadiazole-2-Arylhydrazone Derivatives of Megazol against Trypanosoma cruzi

“…A series of studies dealing with the antitrypanocidal activity of megazol have been reported (13,21), including its use for the treatment of mice infected with the Colombiana strain of T. cruzi, recognized as resistant to nifurtimox and benznidazole (17). However, reports of the toxicity of megazol (29,30) led to the abandonment of its study.…”

“…The 5-nitroimidazole megazol was shown to be highly active against T. cruzi, including strains resistant to benznidazole, in vitro and in vivo (12,17,21) and has become a core structure for the design of new leads for the treatment of Chagas disease. Megazol has been described as a scavenger of trypanothione, the cofactor for trypanothione reductase (23,42).…”

Absence of CD4+T Lymphocytes, CD8+T Lymphocytes, or B Lymphocytes Has Different Effects on the Efficacy of Posaconazole and Benznidazole in Treatment of Experimental AcuteTrypanosoma cruziInfection

“…In contrast, the antiparasitic action of POS was much less affected, with full survival and cure rates close to those of WT treated animals ( Table 1). The greater dependence of BZ activity on B lymphocytes might be related to the BZ mechanism of action, as BZ treatment induces nonspecific damage to its target cells that could expose parasite-specific antigens and induce the B-lymphocyte-mediated humoral immune response (16). The phagocytic activity of mouse peritoneal macrophages against T. cruzi has been shown to increase in infected mice treated with BZ compared with nontreated animals (16).…”

“…The greater dependence of BZ activity on B lymphocytes might be related to the BZ mechanism of action, as BZ treatment induces nonspecific damage to its target cells that could expose parasite-specific antigens and induce the B-lymphocyte-mediated humoral immune response (16). The phagocytic activity of mouse peritoneal macrophages against T. cruzi has been shown to increase in infected mice treated with BZ compared with nontreated animals (16). Additionally, BZ may preferentially target extracellular (trypomastigote) forms of the parasite, which are targets of the antibody-mediated immune response, while POS acts selectively against the proliferative amastigote stages (see above), which are typically not susceptible to antibodies due to their intracellular location.…”

Article Synthesis and Trypanocidal Activity of Novel 2,4,5-Triaryl-N-Hydroxylimidazole Derivatives

“…Megazol [1-methyl-2-(5-amino-1,3,4-thiadiazole)-5-nitroimidazole] is a nitroheterocyclic derivative shown to be highly active against T. cruzi in vitro and in vivo, including strains that are resistant to benznidazole [5][6][7]; thus, it has become a core structure for the design of new drugs for the treatment of Chagas disease. Megazol has been described as a scavenger of trypanothione, the cofactor for trypanothione reductase [8,9].…”