Does Cyclophosphamide Play a Protective Role Against Neuronal Loss in Chronic T. cruzi Infection?

Abstract

In this study, we verified the possible role of cyclophosphamide (CY) in protecting or not against neuronal losses in young and aged male Calomys callosus chronically infected with the MORC-1 strain of Trypanosoma cruzi through numerical quantification of neurons from the myenteric plexus of the colon and quantification of nitric-oxide concentration (NO) during the acute and chronic phase of infection. For this purpose, groups of young C. callosus were infected with the MORC-1 strain of T. cruzi. A group of infected animals received i.p. 0.2 mg/ml genuxal dissolved in distilled water treatment with CY. NO concentration in aged animals displayed reduced levels when compared to those found in young animals. No significant alterations in the number of neurons were observed in young animals, but for aged ones, a protective role of CY in reducing neuron loss was noted, in addition to enhancing the neuronal volume, area, and perimeter. These results suggest that CY administration, depending on the dose and time span, can act as a protective agent against neuronal losses.

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

“…The intervention also acted on the proliferation of splenocytes, reducing the proliferative capacity of these cells when exposed to polyclonal stimuli. Regarding neuronal count, the treatment resulted in protection of these cells both in the esophagus [ 22 , 23 ] and in the colon [ 21 ] in both phases evaluated (10 days of infection and 450 days of infection). Regarding morphometric analyses of esophageal neurons (diameter, perimeter, area, and volume), treatment with cyclophosphamide did not induce any changes when the treated and infected groups were compared with the untreated infected group [ 22 , 23 ].…”

“…However, older animals showed lower values in all parameters analyzed when compared to younger ones [ 23 ]. For colon neurons [ 21 ], the treatment did not induce morphometric changes at 10 days of infection. Only at 450 days of infection, it was observed that the use of cyclophosphamide increased the perimeter, area, and volume of neurons when compared to the respective untreated group.…”

“…Cyclophosphamide, in turn, was used in three articles included in this systematic review [21][22][23]. The authors demonstrate that this intervention was able to induce neuronal protection in the colon and esophagus, as well as reduce the proinflammatory response via NO and the proliferative capacity of splenocytes [21][22][23]. This drug is widely known for its immunosuppressive function and marked cytotoxic effect, especially on lymphocytes [41].…”

“…Cyclophosphamide. Among the eight articles, cyclophosphamide was evaluated in three studies, one focused on the impact of treatment on the colon [21] and the other two on the esophagus [22,23].…”

The Colombian Strain of Trypanosoma cruzi Induces a Proinflammatory Profile, Neuronal Death, and Collagen Deposition in the Intestine of C57BL/6 Mice Both during the Acute and Early Chronic Phase

“…There is a diversity of strains of T. cruzi that have different biological behaviors, mainly related to molecular biology, tissue tropism, and the form of the developed DC [ 15 , 16 ]. While infection in experimental models with strains such as Y [ 5 , 10 ] and MORC-1 [ 17 ] causes intestinal neuronal destruction, strains such as Ninoa, Queretaro [ 18 ], and Brazil [ 19 ], which induce intestinal changes, have not been evaluated for the number of neurons in the intestinal plexuses.…”