The β-blocker carvedilol and the benznidazole modulate the cardiac immune response in the acute infection induced by Colombian strain of the Trypanosoma cruzi

Mem Inst Oswaldo Cruz. 2018 Oct 18;113(11):e180271. doi: 10.1590/0074-02760180271.

Abstract

BACKGROUND The infection led by Trypanosoma cruzi persists in mammalian tissues causing an inflammatory imbalance. Carvedilol (Cv), a non-selective beta blocker drug indicated to treat heart failure and antihypertensive has shown to promote antioxidant and immunomodulatory properties which might improve the inflammation induced by T. cruzi. OBJECTIVES Evaluate the role of Cv on the inflammatory response of C57BL/6 mice acutely infected with the Colombian strain of T. cruzi. METHODS Animals were infected with the Colombian strain of T. cruzi and treated with Cv (25 mg/kg/day), benznidazole (Bz) (100 mg/kg/day) or their combination. On the 28th day of infection and 23 days of treatment, the euthanasia occurred, and the heart preserved for histopathological, oxidative stress (SOD, catalase, TBARs, carbonylated proteins) and plasma (CCL2, CCL5, TNF, IL-10) analyses. Parasitaemia and survival were assessed along the infection. FINDINGS Cv decreased TBARs, but increased the mortality rate, the parasitaemia and the levels of CCL2, CCL5, catalase and the inflammatory infiltrate in the cardiac tissue. Bz led the reduction of the inflammatory infiltrate and circulating levels of oxidative stress and inflammatory mediators in the infected mice. MAIN CONCLUSIONS Our data suggest that Cv, in this experimental model using the Colombian strain of T. cruzi, caused damage to the host.

Publication types

  • Evaluation Study

MeSH terms

  • Acute Disease
  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Carvedilol / pharmacology*
  • Catalase / analysis
  • Chagas Disease / drug therapy*
  • Chagas Disease / parasitology
  • Chagas Disease / pathology
  • Cytokines / blood
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Heart / drug effects*
  • Male
  • Mice, Inbred C57BL
  • Myocardium / pathology
  • Nitroimidazoles / pharmacology*
  • Oxidative Stress / drug effects
  • Parasitemia / parasitology
  • Protein Carbonylation / drug effects
  • Reference Values
  • Reproducibility of Results
  • Superoxide Dismutase / analysis
  • Thiobarbituric Acid Reactive Substances / analysis
  • Time Factors
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma cruzi / drug effects*
  • Trypanosoma cruzi / isolation & purification

Substances

  • Adrenergic beta-Antagonists
  • Cytokines
  • Nitroimidazoles
  • Thiobarbituric Acid Reactive Substances
  • Trypanocidal Agents
  • Carvedilol
  • Catalase
  • Superoxide Dismutase
  • benzonidazole