Increased heart fibrosis and acute infection in a murine Chagas disease model associated with organophosphorus pesticide metabolite exposure

Sci Rep. 2019 Nov 26;9(1):17539. doi: 10.1038/s41598-019-54218-7.

Abstract

Some reports suggest that exposure to organophosphorus (OP) pesticides increases the incidence of infections. Ethylated dialkylphosphates (EtDAPs) are metabolites of OP pesticides widely distributed with immunomodulatory potential. Chagas disease is produced by Trypanosoma cruzi parasites, and resolution of this infection requires the activation of inflammatory macrophages (MΦ), which results in cardiac fibrosis. Some reports indicate that EtDAPs increase the amount of the anti-inflammatory alternatively activated MΦ (M2; CD206+F4/80+). Therefore, we analyzed the course of T. cruzi infection, MΦ profiles from peritoneal exudate cells (PECs), inflammatory cell infiltration and fibrosis in the heart of BALB/c mice exposed to diethyldithiophosphate (DEDTP), diethylthiophosphate (DETP) or diethylphosphate (DEP, 0.01 g/kg), common DAPs produced by OP pesticides, 24 h before infection with T. cruzi. We found that DEDTP increased the parasite burden in blood by 99% at the peak of the infection and enhanced the myocardial damage due to an increase in infiltrated inflammatory cells (induced by DEDTP or DETP) and fibrosis (induced by EtDAPs). In the PECs, exposure to EtDAPs increased the proportion of the MΦ subpopulations of M2a, M2b and M2d, which are associated with tissue repair. These results indicate that exposure to EtDAPs can exacerbate the acute phase of a parasitic infection and increase the long-term damage to the heart.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chagas Cardiomyopathy / chemically induced
  • Chagas Cardiomyopathy / complications*
  • Chagas Disease / complications
  • Disease Models, Animal
  • Environmental Exposure / adverse effects
  • Female
  • Fibrosis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Myocardium / pathology
  • Organophosphate Poisoning / complications
  • Organophosphate Poisoning / pathology
  • Organophosphates / adverse effects
  • Organophosphorus Compounds / adverse effects*
  • Organothiophosphates / adverse effects
  • Pesticides / adverse effects*
  • Pyrrolidines / adverse effects

Substances

  • Organophosphates
  • Organophosphorus Compounds
  • Organothiophosphates
  • Pesticides
  • Pyrrolidines
  • diethyldithiophosphate
  • O,O-diethyl phosphorothionate
  • 1-(2-(dodecyloxy)ethyl)pyrrolidine hydrochloride