Zinc Supplementation: Immune Balance of Pregnancy During the Chronic Phase of the Chagas Disease.

BACKGROUND: Chagas disease or American trypanosomiasis is caused by the protozoan Trypanosoma cruzi and is endemic of the Americas. The control of the disease is restricted to toxic and potentially teratogenic drugs, which limit the use during pregnancy. The use of food supplementation offers a safe and low-cost form to alleviate Chagas disease symptoms, mostly in areas with alimentary risk. For example, zinc demonstrates positive effects in immune response, including in Chagas disease during pregnancy. PURPOSE: This study describes the innate response in pregnant rats chronically infected with T. cruzi and supplemented with zinc. METHODS: Pregnant female Wistar rats, infected with T. cruzi, were treated with 20 mg/kg/day zinc sulfate and euthanized on the 18th day. Samples (plasma, splenocytes, and peritoneal exudate) were collected and several immune parameters (nitric oxide, RT1B, CD80/CD86, MCP-1, CD11b/c, NK/NKT, IL-2, IL-10, INF-cc, and apoptosis) evaluated. RESULTS: Under Zinc supplementation and/or T. cruzi infection, the gestation developed normally. Several innate immune parameters such as RT1B, CD80/CD86, MCP-1 expressing lymphocytes, IL-2, and IL-17 were positively altered, whereas nitric oxide, CD11b/c, NK/NKT, apoptosis, INF-γ, and corticosterone demonstrated a pro-pregnancy pattern. CONCLUSION: Our results indicated that zinc has diverse effects on immune response during pregnancy. An anti-T. cruzi immunity, as well as a pro-gestation response, were observed after zinc supplementation. The complete comprehension of zinc supplementation in pregnancy will base an adequate strategy to alleviate Chagas disease symptoms and propagation, especially for populations from endemic areas.

Is the adaptive immune response in murine Trypanosoma cruzi infection influenced by zinc supplementation?

Chagas disease afflicts 7 to 8 million people worldwide and congenital Chagas' disease usually leads to changes in the maternal environment, culminating in fetal adaptations. Several articles have described the importance of micronutrients on pregnancy, which is sensitive to infections. In Trypanosoma cruzi endemic regions, the Chagas disease is aggravated by the lack of micronutrients in an average diet, to which pregnant women are more susceptible. The aim of this study was to evaluate distinct T cells phenotypes and intracellular cytokines by flow cytometry in pregnant Wistar rats under zinc therapy during experimental Chagas' disease. Twenty female Wistar rats were infected with 1×105 blood trypomastigotes (Y strain) and 30days after infection the animals were mated and grouped: pregnant infected (PI-n=5), pregnant infected/zinc supplied (PIZ-n=5), pregnant control (PC-n=5), control/zinc supplied (PCZ-n=5). Zinc supplementation: 20mg of zinc/Kg/day (gavage) for 18days followed by euthanasia. The immune parameters showed: decreased percentages of CD62LlowCD44high surface marker for infected and treated group (PIZ) when compared to PI (p<0.05). Concerning to T regulatory cells (Treg cells), a significantly lower percentage of splenic Treg cells was found in the infected and treated group (PIZ) as compared to the PI group (p<0.05). The expression of the co-stimulatory molecule CD28+ displayed a significant reduced percentage in TCD8+ for infected and zinc treated group (PIZ) as compared to (PI). The percentages of CD4+/CD11a+ T cells subsets were lower on PIZ as compared to PI. Concerning to CD45RA+ (B lymphocytes) analysis, infected pregnant and treated group (PIZ) showed a significant decrease in CD45RA percentage when compared to (PI) (p<0.05). The intracellular cytokine profiles for TCD4+ and TCD8+ producing IL-4 and IFN-γ revealed that zinc treated and untreated infected pregnant group (PI and PIZ) displayed increased cytokines concentrations as compared to zinc treated and untreated pregnant controls (PC and PCZ). Our data revealed the involvement of zinc as a signaling molecule in the modulation of the inflammatory process and immune response which occurs during pregnancy of T. cruzi infected rats. Zinc acted in a dual fashion, modulating the host's immune response in a way to protect the organism against the deleterious effects of the infection and an overwhelming pro-inflammatory response during pregnancy.

Does L-arginine availability during the early pregnancy alters the immune response of Trypanosoma cruzi infected and pregnant Wistar rats?

Chagas disease induces a strong immune response and L-arginine is an essential amino acid which plays an important role in homeostasis of the immune system. The aims of this study were to evaluate parasitemia, corticosterone levels, production of nitric oxide (NO), fetal morphological measurements, and histology of heart and placenta. Twenty pregnant Wistar rats (180-220 g) were grouped in: pregnant control (PC), pregnant control and L-arginine supplied (PCA), pregnant infected (PI), pregnant infected and L-arginine supplied (PIA). Females were infected with 1×10(5) trypomastigotes of the Y strain (3rd day of pregnancy). Animals were supplied with 21 mg of L-arginine/kg/day during 14 days. PIA showed significant decreased levels of corticosterone and parasitemia. For control groups, any alteration in NO production was found with L-arginine supplementation; for PIA, enhanced nitrite concentrations were observed as compared to PI. Weights and lengths of fetuses were higher in L-arginine treated and infected pregnant rats as compared to untreated ones. Placental weight from the PIA group was significantly increased when compared to PI. In L-arginine treated animals, cardiac tissue showed reduced amastigote burdens. PIA and PI displayed similar placental parasitism. Based on these results, L-arginine supplementation may be potentially useful for the protection against Trypanosoma cruzi during pregnancy.

Zinc and pregnancy: Marked changes on the immune response following zinc therapy for pregnant females challenged with Trypanosoma cruzi.

BACKGROUND & AIMS: The occurrence of infectious disease processes during pregnancy has significant effects on maternal health and can lead to adverse pregnancy outcomes. The aim of the present study was to examine the potential role of zinc treatment during Trypanosoma cruzi infection in pregnant animals. METHODS: Female Wistar rats weighing 180-200 g were used in all experiments. Production of nitric oxide, peritoneal macrophages counts, and concentrations of IFN-γ and TNF-α were measured, and the potential protective effects of zinc on fetal development were assessed at 14-day post-infection. RESULTS: Nitric oxide concentrations were higher in pregnant zinc-treated animals than in their untreated counterparts, despite similar levels of the macrophages, IFN-γ and TNF-α. Zinc therapy was associated with a significant reduction in parasitemia and cardiac parasite burden. Higher placental and birth weights were observed in animals given prenatal zinc supplementation compared to untreated animals. CONCLUSIONS: These data confirm the critical importance of adequate zinc intake during the peri-conceptional period and indicate that zinc has an effective role in preventing adverse outcomes of pregnancy and reducing the risk of common infections such as Chagas' disease.

Effect of zinc supplementation in pregnant mice during experimental Trypanosoma cruzi infection.

Zinc is an essential micronutrient and has significant effects on human growth, development, and immune function. Zinc supplementation or deficiency may affect the course of infection. Zinc enhances immune response against a wide range of viral, bacterial, and parasitic pathogens. In the present study, we investigated the effects of zinc sulphate (ZnSO(4)) supplementation (20mg/kg/day) during pregnancy in mice, Swiss Webster strain infected by the Y strain of Trypanosoma cruzi. Oral supplementation of zinc sulphate in pregnant and non-pregnant infected animals did not affect the count of blood parasites as well as tissue parasitism in the heart, liver, and spleen. Zinc supplementation did not alter female body weight, the length of fetuses and neonates, placental size/weight and mortality rate. Among zinc supplied animals, no significant plasmatic zinc concentrations were observed. Concerning to tissue zinc concentrations, only the liver displayed enhanced values as compared to other organs. For placental parasitism, zinc supplied group displayed a significant decrease in amastigote burdens (P<0.05). However due to the reduced number of parasite burdens in placenta of animals supplied with zinc, these data suggest that zinc was partially effective in up-regulating the host's immune response against parasite, probably attenuating the infection in fetuses.

Dehydroepiandrosterone increases resistance to experimental infection by Trypanosoma cruzi.

Dehydroepiandrosterone (DHEA) enhances immune responses against a wide range of viral, bacterial, and parasitic pathogens. In a previous study, we reported that administration of DHEA significantly decreased the numbers of blood parasites in Trypanosoma cruzi experimental infection. The present study was undertaken to determine the effectiveness of DHEA in reducing the severity of acute phase T. cruzi infection of male and female Wistar rats. Animals were treated subcutaneously with 40 mg/kg body weight/day of DHEA. The concentration of nitric oxide (NO) was determined in spleen peritoneal cavity. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were determined in the sera of uninfected and infected animals. DHEA treatment augments NO production for both sexes after in vitro LPS treatment for uninfected animals. Infection triggered enhanced NO levels although not significant. IL-2 and IFN-gamma were detectable in higher concentrations in treated and infected rats of both genders when compared to untreated controls. These data suggest that DHEA may have a potent immunoregulatory function that can affect the course of T. cruzi infection.

Trypanosoma cruzi: the effects of dehydroepiandrosterone (DHEA) treatment during experimental infection.

The aim of this study was to evaluate the efficacy of the immunomodulator dehydroepiandrosterone (DHEA) in the treatment of Trypanosoma cruzi infection and the possible biochemistry alterations in male and female Wistar rats. DHEA also known as the steroid of multiple actions has attracted distinct medical areas. Prior studies show that DHEA enhances immune responses against a wide range of viral, bacterial and parasitic pathogens. Furthermore, administration of DHEA seems to protect animals against obesity and diabetes. Male animals subcutaneous treated with 40 mg/kg body weight/day of DHEA displayed a significant reduction in blood parasites during parasitaemia peak, when compared to untreated animals (P<0.001). For female group parasitaemia was also reduced although values are not statistically significant (P>0.05). Sexual dimorphism was also observed, since females displayed lesser parasitaemia levels compared to males group treated (P>0.05) and untreated (P<0.001). Enhanced leucocytes number was observed in control females when compared to control males (P<0.05). DHEA treatment did not triggered any significant alterations in leucocytes levels (P>0.05). DHEA administration induced an enhanced number of macrophages in infected male (P<0.01). DHEA administration causes a decrease in glucose (P<0.001). Cholesterol and tryglicerides levels did not display results statistically significant (P>0.05) during the treatment. These results suggest that DHEA treatment enhances the immune response as evidenced here by reduced levels of parasites. Up-regulation of the immune system by exogenous DHEA may be useful in the treatment of American tripanosomiasis.