RESUMO
OBJECTIVE: Apolipoprotein L1 gene (APOL1) G1 and G2 renal risk alleles (RRA) are associated with endstage renal disease in blacks with lupus nephritis (LN). The present study determined frequencies of APOL1 RRA in nonwhite Brazilian patients with LN and controls to assess association with renal outcomes. METHODS: APOL1 RRA were genotyped in 222 healthy blood donors (controls) and 201 cases with LN from 3 outpatient clinics. Two single-nucleotide polymorphisms in the G1 (rs73885319 and rs60910145) and an indel for the G2 (rs71785313) variant were genotyped. RESULTS: The frequency of APOL1 RRA in nonwhite Brazilian LN cases did not differ significantly from healthy controls, and few participants had 2 RRA. In the sample, 84.6% of LN cases and 84.2% of controls had 0 RRA, 13.4% and 15.3% had 1 RRA, and 2.0% and 0.4% had 2 RRA, respectively. LN cases with ≥ 1 APOL1 RRA had similar baseline characteristics and renal responses to treatment, yet faced higher risk for progressive chronic kidney disease (CKD) to an estimated glomerular filtration rate < 30 ml/min/1.73 m2 compared to those with 0 RRA (11.2% with 0, 29.6% with 1; 50% with 2 RRA, p = 0.005). Although glomerular lesions and activity scores on initial kidney biopsy did not differ significantly between individuals based on APOL1 genotype, chronicity scores, tubular atrophy, and interstitial fibrosis were more severe in those with ≥ 1 RRA (p = 0.011, p = 0.002, p = 0.018, respectively). CONCLUSION: Although initial kidney lesions and treatment responses were similar, a single APOL1 RRA in nonwhite Brazilians with LN was associated with increased risk of advanced CKD and possibly more tubulointerstitial damage.
Assuntos
Apolipoproteína L1 , Nefrite Lúpica , Apolipoproteína L1/genética , Predisposição Genética para Doença , Genótipo , Humanos , Nefrite Lúpica/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The aim of this study was to evaluate the therapeutic efficacy of specific avian polyclonal antibodies (IgY) against Trypanosoma cruzi and their interaction with ecto-enzymes of the purinergic system (NTPDase and adenosine deaminase (ADA) activities) in splenic lymphocytes. For this, mice were divided into six groups: three non-infected (A, B, and C) and three infected (D, E, and F). The groups A and D were composed by negative and positive controls, respectively; while the groups B and E were treated prophylactically with IgY (50 mg/kg), and the groups C and F were treated therapeutically with IgY (50 mg/kg). Treatment with IgY reduced parasitemia on day 6 post-infection (PI) compared to the infected control group, but it was similar on day 8 PI. Moreover, infected and treated animals (the groups E and F) did not show neither amastigotes in the cardiac tissue nor cardiac lesions when compared to the positive control group (the group D). The E-NTPDase (ATP and ADP as substrate) and ADA activities in splenic lymphocytes increased significantly in the positive control group (the group D) compared to the negative control group (the group A). The therapeutic treatment of IgY (the group F) was able to prevent the increase of E-NTPDase and E-ADA activities compared to the positive control group (the group D), but this finding was not observed in animals that received the prophylactic treatment (the group E). The therapeutic treatment of IgY may be considered an interesting approach to improve the immune response of mice experimentally infected by T. cruzi.
Assuntos
Adenosina Desaminase , Anticorpos Antiprotozoários/farmacologia , Proteínas Aviárias/farmacologia , Doença de Chagas , Imunoglobulinas/farmacologia , Proteínas de Protozoários , Baço , Trypanosoma cruzi , Adenosina Desaminase/imunologia , Adenosina Desaminase/metabolismo , Animais , Doença de Chagas/tratamento farmacológico , Doença de Chagas/enzimologia , Doença de Chagas/imunologia , Galinhas , Feminino , Linfócitos/enzimologia , Linfócitos/imunologia , Linfócitos/patologia , Camundongos , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/metabolismo , Baço/enzimologia , Baço/imunologia , Baço/parasitologia , Baço/fisiologia , Trypanosoma cruzi/enzimologia , Trypanosoma cruzi/imunologiaRESUMO
The aim of this study was to investigate the effects of Trypanosoma evansi infections on arterial blood gases of experimentally infected rats. Two groups with eight animals each were used; group A (uninfected) and group B (infected). Infected animals were daily monitored through blood smears that showed high parasitemia with 30 trypanosomes per field (1000×) on average, 5 days post-infection (PI). Arterial blood was collected at 5 days PI for blood gas analysis using an automated method based on dry-chemistry. Hydrogen potential (pH), partial oxygen pressure (pO2), oxygen saturation (sO2), sodium (Na), ionic calcium (Ca ionic), chlorides (Cl), partial dioxide carbon pressure (pCO2), base excess (BE), base excess in the extracellular fluid (BEecf), bicarbonate (cHCO3), potassium (K), lactate, and blood total dioxide the carbon (tCO2) were evaluated. The levels of pH, pCO2, BE, BEecf, cHCO3, and tCO2 were significantly decreased (P < 0.05) in group B compared to group A. Additionally, the same group showed increases in Cl and lactate levels when compared to uninfected group. Therefore, it is possible to state that the infection caused by T. evansi led to alterations in the acid-base status, findings that are correlated to metabolic acidosis.
RESUMO
This study aimed to verify the effect of the treatment with A. satureioides essential oil (free and nanoencapsulated forms) and diminazene aceturate on hematological and biochemical variables in rats infected by Trypanosoma evansi. The 56 rats were divided into seven groups with eight rats each. Groups A, C and D were composed by uninfected animals, and groups B, E, F and G were formed by infected rats with T. evansi. Rats from groups A and B were used as negative and positive control, respectively. Rats from the groups C and E were treated with A. satureioides essential oil, and groups D and F were treated with A. satureioides nanoencapsulated essential oil. Groups C, D, E and F received one dose of oil (1.5 mL kg(-1)) during five consecutive days orally. Group G was treated with diminazene aceturate (D.A.) in therapeutic dose (3.5 mg kg(-1)) in an only dose. The blood samples were collected on day 5 PI for analyses of hematological (erythrocytes and leukocytes count, hemoglobin concentration, hematocrit, mean corpuscular and mean corpuscular hemoglobin concentration) and biochemical (glucose, triglycerides, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, urea and creatinine) variables. A. satureioides administered was able to maintain low parasitemia, mainly the nanoencapsulated form, on 5 days post infection. On the infected animals with T. evansi treated with A. satureioides essential oil (free and nanocapsules) the number of total leucocytes, lymphocytes and monocytes present was similar to uninfected rats, and different from infected and not-treated animals (leukocytosis). Treatment with A. satureioides in free form elevated levels of ALT and AST, demonstrating liver damage; however, treatment with nanoencapsulated form did not cause elevation of these enzymes. Finally, treatments inhibited the increase in creatinine levels caused by infection for T. evansi. In summary, the nanoencapsulated form showed better activity on the trypanosome; it did not cause liver toxicity and prevented renal damage.
Assuntos
Achyrocline/química , Diminazena/análogos & derivados , Óleos Voláteis/uso terapêutico , Óleos de Plantas/uso terapêutico , Tripanossomicidas/uso terapêutico , Tripanossomíase/tratamento farmacológico , Animais , Biomarcadores/sangue , Análise Química do Sangue , Diminazena/administração & dosagem , Diminazena/uso terapêutico , Cães , Feminino , Testes Hematológicos , Rim/fisiologia , Fígado/fisiologia , Nanocápsulas , Óleos Voláteis/administração & dosagem , Óleos Voláteis/química , Parasitemia/parasitologia , Óleos de Plantas/administração & dosagem , Óleos de Plantas/química , Ratos , Ratos Wistar , Tripanossomicidas/administração & dosagem , Trypanosoma/efeitos dos fármacos , Tripanossomíase/sangueRESUMO
The aim of this study was to evaluate the nitric oxide (NO) levels, and oxidative and antioxidant markers of lambs experimentally and naturally infected by Haemonchus contortus, and its relation to lesions in the abomasum. For experimental study, a total of 14 healthy lambs were divided into two groups with seven animals each. Group A represented the uninfected animals (control), and Group B was formed by infected animals with 15,000 larvae of H. contortus. Blood was collected on days 15, 45, and 75 post-infection (PI) to obtain serum for biochemical analysis: lactate dehydrogenase (LDH), nitrite/nitrate (NOx), advanced oxidation protein products (AOPP), and ferric reducing ability of plasma (FRAP). Parasitological stool examination (eggs per gram of feces--EPG) was performed on days 15, 45, and 75 PI to verify the evolution of the infection. On day 15 PI EPG was negative, but on days 45 and 75 PI the EPG was positive for animals from Group B. In the three periods evaluated it was observed an increase of LDH levels in serum of lambs infected with gastrointestinal nematodes, but on the other hand NOx levels were reduced on the same periods in infected animals. The AOPP and FRAP levels did not differ between groups on days 15 and 45 PI, but increased significantly on day 75 PI in infected lambs. The same variables were studied in 10 lambs naturally infected with helminths, where more than 97% corresponded to H. contortus (hematocrit and EPG values were 18.8 ± 2.5% and 7120 ± 2940, respectively). Similar to the experimental study, the levels of NOx reduced, and the levels of LDH, FRAP, and AOPP increased in serum of this animal associated inflammatory infiltrate in the mucosa of the abomasum. Therefore, during the infection by H. contortus it was observed alterations in oxidative markers, indicators of cell lesion confirmed by histological examination of the abomasum, and consequently there were changes in antioxidant levels, with the purpose of cell protection. We also conclude that helminth infection interferes with the nitric oxide metabolism.
Assuntos
Abomaso/parasitologia , Hemoncose/veterinária , Haemonchus/patogenicidade , Óxido Nítrico/metabolismo , Estresse Oxidativo , Doenças dos Ovinos/parasitologia , Abomaso/metabolismo , Abomaso/patologia , Produtos da Oxidação Avançada de Proteínas/sangue , Animais , Animais Recém-Nascidos , Antioxidantes/metabolismo , Biomarcadores/sangue , Modelos Animais de Doenças , Fezes/parasitologia , Hemoncose/sangue , Hemoncose/parasitologia , Hemoncose/patologia , Haemonchus/classificação , L-Lactato Desidrogenase/sangue , Masculino , Nitratos/sangue , Nitritos/sangue , Oxirredução , Ovinos , Doenças dos Ovinos/sangue , Doenças dos Ovinos/patologia , Fatores de TempoRESUMO
The aim of this study was to evaluate the relationship between testicular lesions and hormone levels in rats experimentally infected with Trypanosoma evansi. For that, the measurement of reproductive hormones, histopathology and biomarkers of cellular injury were carried out in twenty-four animals, which were divided into two groups with 12 animals each. Group A was the negative control, or uninfected, while group B was composed by animals infected with T. evansi. Both groups were divided again into two other subgroups (n=6), from which serum and testicular fragments were collected on days 5 (A1 and B1) and 15 (A2 and B2) post-infection (PI). The morphological analysis showed increased alterations of head and tail of sperm in infected rats when compared with those of the control group. A significant reduction (P<0.01) in the levels of LH, FSH, testosterone and estradiol, associated with an increase in cortisol, was observed in serum of group B when compared with negative control. Additionally, NOx, lipid peroxidation and protein oxidation were enhanced in testicles, indicating the occurrence of cellular lesion. On histopathology, it was possible to observe testicular degeneration, among other disorders in infected animals. Therefore, based on these results, it is possible to conclude that the experimental infection with T. evansi caused changes in the levels of the main hormones of male rats associated with cellular injury.
Assuntos
Espermatozoides/parasitologia , Testículo/parasitologia , Tripanossomíase/sangue , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Hidrocortisona/sangue , Hormônio Luteinizante/sangue , Masculino , Parasitemia , Progesterona/sangue , Ratos Wistar , Testículo/fisiopatologia , Tripanossomíase/fisiopatologiaRESUMO
The aim of this study was to evaluate the effect of zinc supplementation on the ecto-adenosine deaminase activity (E-ADA), zinc seric levels and cytokines (TNF-α, IL-1, IL-6, and IL -10) on rats experimentally infected by Trypanosoma evansi. Four groups with 10 rats each were used as negative controls (groups A and B), while the animals from the groups C and D were infected intraperitoneally with 0.1 mL of cryopreserved blood containing 1.4 × 10(4) of trypanosomes. Animals of groups B and D received two doses of Zinc (Zn) at 5 mg kg(-1), subcutaneously, on the 2nd and 7th day post-infection (PI). Blood samples were collected on days 5 (n = 5) and 15 PI (n = 5). Zn supplementation was able to increase the rat's longevity and to reduce their parasitemia. It was observed that seric Zn levels were increased on infected animals under Zn supplementation. Animals that were infected and supplemented with Zn showed changes in E-ADA activity and in cytokine levels (P < 0.05). Zn supplementation of healthy animals (Group B), increased the E-ADA activity, as well as reduced the concentration of cytokines. Infected animals from groups C and D showed increased levels of cytokines. Finally, we observed that Zn supplementation led to a modulation on cytokine's level in rats infected by T. evansi, as well as in E-ADA activity.
Assuntos
Adenosina Desaminase/sangue , Citocinas/sangue , Trypanosoma/imunologia , Tripanossomíase/imunologia , Tripanossomíase/patologia , Zinco/administração & dosagem , Zinco/sangue , Animais , Modelos Animais de Doenças , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/sangue , Longevidade , Carga Parasitária , Parasitemia , Ratos Wistar , Soro/química , Análise de SobrevidaRESUMO
The aim of this study was to verify the trypanocidal effectiveness of aqueous, methanolic, and ethanolic extracts of Achyrocline satureioides against Trypanosoma evansi in vitro. A. satureioides extracts, known as macela, were used on trypomastigotes at different concentrations (1, 5, 10, 50, 100, 500, and 1,000 µg/ml) and exposure times (0, 1, 3, 6, and 9 hr). A dose-dependent effect was observed when the 3 extracts were tested. The concentrations of 1, 5, and 10 µg/ml were not able to kill trypomastigotes until 3 hr after exposure, and the highest concentrations (500 and 1,000 µg/ml) were able to kill all trypomastigotes after 1 hr. When the time of exposure was increased up to 9 hr, the concentrations at 50 and 100 µg/ml were 100% effective to 3 extracts. The chemical analysis of the extracts revealed the presence of flavonoids, a trypanocidal compound already described. Based on the results, we can conclude that the A. satureioides extracts exhibit trypanocidal effects.
Assuntos
Achyrocline/química , Antimaláricos/farmacologia , Extratos Vegetais/farmacologia , Trypanosoma/efeitos dos fármacos , Antimaláricos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Extratos Vegetais/isolamento & purificação , Fatores de TempoRESUMO
Objective. This study aimed to test the effectiveness of copaiba, andiroba and aroeira essential oils for controlling trypanosomosis by Trypanosoma evansi with mice as experimental model. Materials and methods. Sixty-six mice were divided into eleven groups (A to L) with six animals each. Group A was the unique composed by healthy and uninfected animals (negative control). Animals in groups B to L were inoculated with 0.1 mL of blood containing 2.7 x 10(6) trypanosomes. Group B was used as a positive control without treatment. In experiment were tested copaiba (C, D and E), andiroba (F, G and H) and aroeira (I, J and L) oils at doses of 0.6, 0.8 and 1.0 mL kg-1 to infected mice (T. evansi). Results. These protocols did not provide curative efficacy; however, the mice treated with highest dose of copaiba showed a significant increase in the longevity when compared others groups. Conclusions. Previously in our studies, these essential oils have shown trypanocidal activity in vitro, but when they were tested in vivo in mice infected with T. evansi, this trypanocidal activity, or the curative effect was not found, being only able to prolong the lifespan of the animals treated with copaiba oil.
Objetivo. Este estudio tuvo como objetivo evaluar la eficacia de los aceites esenciales de copaiba, andiroba y aroeira para controlar la tripanosomiasis por Trypanosoma evansi con ratones como modelo experimental. Materiales y métodos. Sesenta y seis ratones se dividieron en once grupos (A a L) con seis animales cada uno. Grupo A fue el único compuesto por los animales sanos y no infectadas (control negativo). Los animales en los grupos B a L fueron inoculados con 0,1 mL de sangre que contiene 2,7 x 10(6) tripanosomas. Grupo B se utilizó como control positivo, sin tratamiento. En el experimento se pusieron a prueba los aceites de copaiba (C, D y E), andiroba (F, G y H) y aroeira (I, J y L) en una dosis de 0,6, 0,8 y 1,0 ml kg-1 en ratones infectados (T. evansi). Resultados. Estos protocolos no proporcionan una eficacia curativa; sin embargo, los ratones tratados con la dosis más alta de copaiba mostraron un aumento significativo en longevidad en comparación con otros grupos. Conclusiones. De forma previa en nuestros estudios, estos aceites esenciales han demostrado actividad tripanocida in vitro, pero cuando se ensayaron in vivo en ratones infectados con T. evansi, no se encontró esta actividad tripanocida o el efecto curativo, siendo sólo capaz de prolongar la vida de los animales tratados con aceite de copaiba.
Assuntos
Técnicas In Vitro , Longevidade , Camundongos , ÓleosRESUMO
This study aimed to evaluate the effect of tea tree oil (TTO - Melaleuca alternifolia) on hepatic and renal functions, and the immune response of rats infected by Trypanosoma evansi. A pilot study has shown that rats treated with TTO orally (1 ml kg(-1)) had increased survival rate without curative effect. In order to verify if increased longevity was related to a better immune response against T. evansi when using tea tree oil, a second experiment was conducted. Thus, twenty-four rats were divided into four groups. The groups A and B were composed of uninfected animals, and the groups C and D had rats experimentally infected by T. evansi. Animals from the groups B and D were treated orally with TTO (1 ml kg(-1)) for three days. Blood samples were collected to verify humoral response analysis for immunoglobulins (IgA, IgM, IgE, and IgG) and cytokines (TNF-α, INF-γ, IL-1, IL-6, IL-4, and IL-10) at days 0, 3, 5 and 15 post-infection (PI). TTO treatment caused changes in the immunoglobulins and cytokines profile, as well as the course of T. evansi infection in rats. It was found that the TTO was not toxic, i.e., hepatic and renal functions were not affected. Therefore, it is possible to conclude that TTO influences the levels of inflammatory mediators and has trypanocidal effect, increasing life expectancy of rats infected by T. evansi.