Down regulation of IL-10 and TGF-ß1 mRNA expression associated with reduced inflammatory process correlates with control of parasitism in the liver after treatingL. infantuminfected dogs with the LBMPL vaccine therapy.

The liver plays an important role in human and canine visceral leishmaniasis, then it is considered as target to understand the mechanisms involved in the parasite control and a parameter to assess therapeutic responses. In this sense, our study focuses on evaluating the major alterations in the liver by histological (morphometric parenchyma inflammation/semi-quantitative portal inflammation), immunohistochemical assays (parasitism), and qPCR (parasitism and cytokine gene expression) in Leishmania infantum naturally infected dogs and treated with LBMPL vaccine. Animals were divided in four groups: NI group (n = 5): uninfected and untreated dogs; INT group (n = 7): L. infantum-infected dogs and not treated; MPL group (n = 6): L. infantum-infected dogs that received only monophosphoryl lipid A adjuvant, and LBMPL group (n = 10): L. infantum-infected dogs that received treatment with the vaccine composed by L. braziliensis disrupted promastigotes associated with MPL adjuvant. Ninety days after the end of treatments, the dogs were euthanized, and the liver was collected for the proposed evaluations. Significantly lower portal inflammatory reactions, and lower parenchyma inflammation were observed in the LBMPL group compared to INT and MPL groups. iNOS mRNA expression was higher in LBMPL group and in contrast, IL-10 and TGF-ß1 mRNA expression was lower in this group when compared to INT group. Immunohistochemical and qPCR analysis showed significant parasite load reduction in LBMPL group compared to INT and MPL animals. Our data suggest that in naturally Leishmania-infected dogs, LBMPL vaccine reduces the damage in the hepatic tissue, being able to attenuate the type 2 immune response. It could be associated with a marked reduction in the parasitism decreasing liver inflammation in treated dogs. Along with previously obtained data, our results suggest that LBMPL vaccine can significantly contribute to the therapy strategy for L. infantum infected dogs.

Hepatoprotective, antioxidant, anti-inflammatory, and antiviral activities of silymarin against mayaro virus infection.

Infection caused by Mayaro virus (MAYV) is responsible for causing acute nonspecific fever, in which the majority of patients develop incapacitating and persistent arthritis/arthralgia. Mayaro fever is a neglected and underreported disease without treatment or vaccine, which has gained attention in recent years after the competence of Aedes aegypti to transmit MAYV was observed in the laboratory, coupled with the fact that cases are being increasingly reported outside of endemic forest areas, calling attention to the potential of an urban cycle arising in the near future. Thus, to mitigate the lack of information about the pathological aspects of MAYV, we previously described the involvement of oxidative stress in MAYV infection in cultured cells and in a non-lethal mouse model. Additionally, we showed that silymarin, a natural compound, attenuated MAYV-induced oxidative stress and inhibited MAYV replication in cells. The antioxidant and anti-MAYV effects prompted us to determine whether silymarin could also reduce oxidative stress and MAYV replication after infection in an immunocompetent animal model. We show that infected mice exhibited reduced weight gain, hepatomegaly, splenomegaly, anaemia, thrombocytopenia, leukopenia, increased liver transaminases, increased pro-inflammatory cytokines and liver inflammation, increased oxidative damage biomarkers, and reduced antioxidant enzyme activity. However, in animals infected and treated with silymarin, all these parameters were reversed or significantly improved, and the detection of viral load in the liver, spleen, brain, thigh muscle, and footpad was significantly reduced. This work reinforces the potent hepatoprotective, antioxidant, anti-inflammatory, and antiviral effects of silymarin against MAYV infection, demonstrating its potential against Mayaro fever disease.

L-arginine supplementation increases cardiac collagenogenesis in mice chronically infected with Berenice-78 Trypanosoma cruzi strain.

Chagas disease, caused by Trypanosoma cruzi, is a major neglected tropical disease that occurs mainly as chronic infection and systemic infection. Currently, there is no suitable and effective drug to treat this parasitic disease. Administration of nutrients with immunomodulatory properties, such as arginine and nitric oxide radicals, may be helpful as antiparasitic therapy. In this study, we evaluated the effects of arginine supplementation during the acute phase of infection under the development of chronic Chagas' heart disease in Swiss mice inoculated with the Berenice-78 strain of T. cruzi. The effectiveness of arginine was determined by daily detection of the parasite in the blood and long-term serum levels of nitric oxide and tumor necrosis factor-alpha, in addition to evaluation of heart tissue damage. Arginine could flatten parasitemia and prevent elevation of tumor necrosis factor-alpha in T. cruzi-infected mice. Regarding chronic inflammatory myocardial derangements, similar findings were verified among T. cruzi-infected groups. Arginine promoted collagenogenesis in the heart muscle tissue of T. cruzi-infected arginine-supplemented group. These data show the paradoxical benefits of arginine in improving the outcome of Chagas chronic cardiomyopathy.

Antioxidant potential of Buriti (Mauritia flexuosa) pulp flour in diabetic rats

Buriti pulp flour (BPF) contains significant levels of antioxidants. This study evaluated the effect of BPF on biomarkers of oxidative damage in the liver, heart, and pancreas of diabetic rats. The chemical composition, antioxidant capacity, and polyphenol content of BPF were determined. Thirty-six female Fisher rats were divided into four groups: control (C); control + BPF (CB); diabetic (D); diabetic + BPF (DB). Diabetes was induced by treatment with streptozotocin. Thirty days after the induction of diabetes, glucose, total cholesterol and triacylglycerides serum levels, aminotransferase and paraoxonase activities were evaluated. Oxidative damage to lipids and proteins was assessed through thiobarbituric acid reactive substances (TBARS) and protein carbonyl analyses, respectively. Histopathological analyses were also performed. BPF contained high concentrations of phenolic compounds, lipids, and fibers, and exhibited a high capacity to neutralize the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Diabetes was evidenced by equivalent high levels of glucose in plasma from rats in the D and DB groups. Diabetic rats in both groups also presented the same increased activity of aminotransferases. Protein carbonyl levels were increased in liver, heart, and pancreas in the D compared with C group. Although treatment with BPF did not result in any histopathological alterations, it reduced significantly the levels of TBARS in the heart and protein carbonyls in the liver and heart. No effect on blood glucose and tissue histology was observed following treatment with BPF. However, BPF diminished oxidative damage in liver and heart, indicating a possible antioxidant potential in vivo, in addition to in vitro(AU)

La harina de pulpa buriti (BPF) contiene niveles significativos de antioxidantes. Este estudio evaluó el efecto del BPF en biomarcadores de daño oxidativo en el hígado, el corazón y el páncreas de ratas diabéticas. Se determino la composición química, la capacidad antioxidante y el contenido de polifenoles del BPF. Treinta y seis ratas Fisher fueron divididas en cuatro grupos: Control (C); Control + BPF (CB); Diabético (D); Diabético + BPF (DB). La diabetes fue inducida por tratamiento con estreptozotocina. Treinta dias después de la inducción de la diabetes, se evaluaron los niveles séricos de glucosa, colesterol total y triacilglicéridos, y las actividades de aminotransferasa y paraoxonasa. El daño oxidativo a lípidos y proteínas se evaluó a través de sustancias reactivas al ácido tiobarbitúrico (TBARS) y análisis de proteínas carboniladas respectivamente. También se realizaron análisis histopatológicos. El BPF contenía altas concentraciones de compuestos fenólicos, lípidos y fibras, y exhibía una alta capacidad para neutralizar el radical 2,2-difenil-1-picrilhidracil (DPPH). La diabetes se evidenció por altos niveles de glucosa en plasma de ratas en los grupos D y DB. Las ratas diabéticas en ambos grupos también presentaron la misma actividad aumentada de las aminotransferasas. Los niveles de proteínas carboniladas se incrementaron en el hígado, el corazón y el páncreas en el grupo D en comparación con el C. Aunque el tratamiento con BPF no dio lugar a alteraciones histopatológicas, redujo significativamente los niveles de TBARS en el corazón y las proteínas carboniladas en el hígado y el corazón. No se observo ningún efecto sobre la glucosa en la sangre y la histología de tejidos después del tratamiento con BPF. Sin embargo, el BPF disminuyó el daño oxidativo en el hígado y el corazón, lo que indica un posible potencial antioxidante in vivo, además de in vitro(AU)

Effects of the interaction of diabetes and iron supplementation on hepatic and pancreatic tissues, oxidative stress markers, and liver peroxisome proliferator-activated receptor-α expression.

This study evaluated the effects of the interaction of diabetes and a carbonyl iron supplemented on hepatic and pancreatic tissues, oxidative stress markers and liver peroxisome proliferator-activated receptor-α expressions. Hamsters were divided: Control which received a standard AIN 93 diet; Control Iron, composed of control animals that received a diet with 0.83% carbonyl iron; Diabetic, composed of animals that received a injection of streptozotocin (50 mg/kg, intraperitoneal) on day 35; and Diabetic Iron composed of streptozotocin treated animals that received a diet supplemented with carbonyl iron. Diabetes increased the glucose level and reduced triglycerides. Diabetic Iron group showed higher levels of glucose and serum triglycerides as compared to the Diabetic group. Diabetes decreased mRNA levels of peroxisome proliferator-activated receptor-α. Iron attenuated the diabetes induced down regulation of peroxisome proliferator-activated receptor-α mRNA. Moreover, diabetes increased carbonyl protein and decreased glutathione levels and catalase activity, while iron attenuated the increase in levels of carbonyl protein and attenuated the decrease in those of glutathione level and catalase activity. Histological analysis shows that supplementation iron caused an increase in the size of the islets in Control Iron. The results show that iron does not aggravated liver oxidant/antioxidant status and peroxisome proliferator-activated receptor-α expression in diabetic hamsters.