Abstract
BackgroundChagas disease is a neglected tropical disease caused by Trypanosoma cruzi. Despite the vast number of studies evaluating the pathophysiological mechanisms of the disease, the influence of parasite burden on kidney lesions remains unclear. Thus, the main goal of this work was to evaluate the effect of T. cruzi infection on renal function and determine whether there was a correlation between parasite load and renal injury using an acute experimental model of the disease.Methodology/Principal FindingsLow, medium and high parasite loads were generated by infecting C57BL/6 mice with 300 (low), 3,000 (medium) or 30,000 (high) numbers of “Y” strain trypomastigotes. We found that mice infected with T. cruzi trypomastigotes show increased renal injury. The infection resulted in reduced urinary excretion and creatinine clearance. We also observed a marked elevation in the ratio of urine volume to kidney and body weight, blood urea nitrogen, chloride ion, nitric oxide, pro- and anti-inflammatory cytokines and the number of leukocytes in the blood and/or renal tissues of infected mice. Additionally, we observed the presence of the parasite in the cortical/medullary and peri-renal region, an increase of inflammatory infiltrate and of vascular permeability of the kidney. Overall, most renal changes occurred mainly in animals infected with high parasitic loads.Conclusions/SignificanceThese data demonstrate that T. cruzi impairs kidney function, and this impairment is more evident in mice infected with high parasitic loads. Moreover, these data suggest that, in addition to the extensively studied cardiovascular effects, renal injury should be regarded as an important indicator for better understanding the pan-infectivity of the parasite and consequently for understanding the disease in experimental models.
Highlights
The kidneys are responsible for a diverse range of functions including homeostatic, regulatory and excretory functions as well as hormone production
We evaluated the development of T. cruzi parasitemia in C57BL/6 wild type mice inoculated subcutaneously with low (300), medium (3,000) or high doses (30,000) of T. cruzi trypomastigotes
Animals infected with low or medium loads of trypomastigotes survived throughout the period of the experiment, while mice infected with high parasite loads showed a mortality of approximately 30%, with the animals dying beginning at 21 days post-infection (Figure 1B)
Summary
The kidneys are responsible for a diverse range of functions including homeostatic, regulatory and excretory functions as well as hormone production. Chagas disease, discovered by Carlos Chagas in 1909 [4], is a severe American parasitosis caused by the hemoflagellate protozoan Trypanosoma cruzi This disease is a major public health concern in Latin America, where it is estimated to affect 12–14 million people [5]. In non-endemic countries, Chagas disease has been reported as consequence mainly of the migration of infected people from endemic countries (Latin America) to these areas [6]. This disease causes the death of approximately 21,000 people each year worldwide [7]. The main goal of this work was to evaluate the effect of T. cruzi infection on renal function and determine whether there was a correlation between parasite load and renal injury using an acute experimental model of the disease
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