Cyclophosphamide-induced immunosuppression protects cardiac noradrenergic nerve terminals from damage by Trypanosoma cruzi infection in adult rats

Abstract

Trypanosoma cruzi-infected juvenile rats develop severe cardiac sympathetic denervation in parallel with acute myocarditis. This aspect has not been studied in adult rats, thought to be resistant to this infection. The mechanism involved in T. cruzi-induced neuronal damage remains to be completely elucidated. In juvenile rats, the mortality during the acute phase depends on T. cruzi populations, ranging from 30% to 100%. Therefore, studies of mechanisms through hazardous procedures such as immunosuppression are restricted. The current paper shows that adult rats infected with T. cruzi (Y strain) develop severe acute myocarditis and cardiac sympathetic denervation, despite null mortality and virtual absence of patent parasitaemia followed by negative haemoculture. Recovery from the myocarditis and denervation occurred but PCR studies showed persistence of parasite DNA at least until day 111 post inoculation. Immunosuppression by cyclophosphamide treatment increased the parasitaemia, prevented the acute myocarditis and the sympathetic denervation without significant alteration of the myocardial parasitism. These results argue against a direct role for parasite-derived products and implicate the inflammatory cells in the denervation process. As previous studies in juvenile animals have discarded an essential role for radiosensitive cells, the macrophages remain as the possible effectors for the T. cruzi-induced neuronal damage.

Benznidazole alters the pattern of Cyclophosphamide-induced reactivation in experimental Trypanosoma cruzi-dependent lineage infection

“…Among patients with AIDS it was also observed an absence of reactivation (Pacheco et al, 1998) as well as an asymptomatic reactivation during the chronic Chagas disease which was detected by the increasing of blood parasitism (Sartori et al, 2002). Reactivation of the disease has been also demonstrated in experimental animals chronically infected with T. cruzi submitted to different immunosuppressive drugs which showed myocarditis and an increase of parasitemia and mortality (Guerra et al, 2001;Brener and Chiari, 1971).…”

Neuroprotective Treatments for Digestive Forms of Chagas Disease in Experimental Models: A Systematic Review

“…In both mice [ 44 – 46 ] and dogs [ 47 ], the intervention increased the myocarditis process established by the infection. However, for rats, the opposite was observed, with cyclophosphamide preventing acute myocarditis and sympathetic denervation, indicating that the inflammatory process may be one of the pathways of neuronal death [ 48 ]. The differences found in the studies may be due to the difference in the therapeutic regimen (concentration and treatment time), the experimental models used, the parasite strains, and the inoculum.…”

Could Cyclophosphamide Exert a Protective Role Avoiding Esophagic Neuron Loss in Calomys callosus Infected with Trypanosoma cruzi?

“…Each animal was i.p. treated with 0.2 ml of this solution 1 week prior to the animal's death [19]. Calomys callosus were kept five per cage, with environment temperature and day/night 12/12 h with water and commercial rodent diet ad libitun until they reach the 15th month of infection, with the animals inspected monthly by a veterinary assistant to check their health status.…”