IL-33 in obesity: where do we go from here? de Oliveira, Marcos Felipe Andrade; Talvani, André; Rocha-Vieira, Etel
Inflammation research,
03/2019, Letnik:
68, Številka:
3
Journal Article
We compared the relevance of ibuprofen, vitamins C and E to control oxidative/nitrosative stress and heart disease in mice infected by Trypanosoma cruzi. Swiss mice were randomized into five groups: ...control, uninfected; infected without treatment; and infected treated with vitamins C, E or ibuprofen. Animals were inoculated with 2000 trypomastigote forms of T. cruzi. After 20 days, infected mice presented reduced vitamin C and E tissue levels, high cytokines (interferon gamma, tumour necrosis factor-α, interleukin 10 and chemokine ligand 2), prostaglandin F2α (PGF2α ) and nitric oxide (NO) cardiac production, intense myocarditis and reactive tissue damage, which was directly correlated with the intensity of the inflammatory infiltrate and the degree of pathological cardiac remodelling. Vitamins C and E supplementation were irrelevant to counteract reactive tissue damage and myocarditis in infected animals. Conversely, ibuprofen reduced tissue levels of cytokines, PGF2α and NO, as well as lipid and protein oxidation, antioxidant enzyme activity and the cardiac damage, without interfering with heart parasitism. Our results do not support the applicability of vitamin C and E supplementation in the management of acute Chagas cardiomyopathy. By controlling the inflammatory infiltrate, anti-inflammatory-based therapy proved to be a more rational strategy than a direct antioxidant therapy in attenuating oxidative/nitrosative stress and cardiac damage.
The physician Carlos Chagas (1879-1934) described the protozoan parasite
and discovered a new illness named American trypanosomiases or Chagas disease (Chagas, 1909) ....
Mechanical ventilation (MV) is a tool used in critical patient care. However, it can trigger inflammatory and oxidative processes capable of causing or aggravating lung injuries, which is known as ...ventilator-induced lung injury (VILI). Hesperidin is a flavonoid with antioxidant and anti-inflammatory properties in various diseases. The role of hesperidin in the process triggered by MV is poorly studied. Thus, we hypothesize hesperidin could protect the lung of mice submitted to mechanical ventilation. For that, we evaluated cell viability and reactive oxygen species (ROS) formation in macrophages using different hesperidin concentrations. We observed hesperidin did not reduce cell viability, however; it attenuated the production of intracellular ROS in cells stimulated with lipopolysaccharide (LPS). We further evaluated the effects of hesperidin in vivo in animals submitted to MV. In the bronchoalveolar lavage fluid, there were higher levels of macrophage, lymphocyte and neutrophil counts in animals submitted to MV, indicating an inflammatory process. In the lung tissue, MV induced oxidative damage and increased myeloperoxidase activity, though the antioxidant enzyme activity decreased. MV also induced the production of the inflammatory mediators CCL-2, TNF-α and IL-12. Pretreatment with hesperidin resulted in less recruitment of inflammatory cells to the airways and less oxidative damage. Also, it reduced the formation of CCL-2 and IL-12. Our results show pretreatment with hesperidin can protect the lungs of mice submitted to mechanical ventilation by modulating the inflammatory response and redox imbalance and may act to prevent MV injury.
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•Hesperidin promotes a reduction in intracellular ROS production in macrophages.•Short-term mechanical ventilation with high tidal volume causes acute lung injury.•Hesperidin pre-treatment resulted in less recruitment of inflammatory cells.•Hesperidin reduced oxidative damage and improved antioxidant defense.
This study describes the role of parasite clearance time induced by benznidazole, fexinidazole and posaconazole treatments upon mice infection with a benznidazole-resistant Trypanosoma cruzi strain ...in the pathological outcomes. Trypanosoma cruzi-infected mice were treated with different drugs and parasite clearance time was detected by blood and tissue qPCR, to determine the dynamic relationship between the efficacy of the treatments and the intensity of heart lesion/serum inflammatory mediators. Our results indicate that anti-T. cruzi treatments were able to reduce parasite replication and consequently induce immunomodulatory effects, where the degree of the immunopathology prevention was related to the time of parasite clearance induced by different treatments. Nevertheless, in benznidazole and posaconazole treatments, parasite rebounding was detected with parasitism reaching levels similar to infected and non-treated mice; the time for parasitic rebound being earlier among benznidazole-treated mice. In parallel, an increase of cardiac lesions and plasma chemokine levels was also detected and was more accentuated in benznidazole-treated animals. Interestingly, in the presence of parasitological cure (fexinidazole treatment), basal levels of these inflammatory mediators were evidenced as well as an absence of cardiac inflammation or fibrosis. Overall, our data indicate that all treatments have positive effects on the clinical evolution of T. cruzi infection, with success in preventing cardiac alterations being drug-dependent.
Background
Congenital toxoplasmosis (CT) is caused by placental transfer of
Toxoplasma gondii
to the fetus, which can generate neurological, neurocognitive deficits, or death. Appropriate preventive ...strategies are required for infection-related risk factors. This study assessed the prevalence of
T. gondii
infection and the factors associated with CT in pregnant women with assistance from the Public Health Service at Ouro Preto, Brazil.
Methods
This cross-sectional study was conducted between April and December 2020. Pregnant women (n=131) aged between 13 and 46 years, were recruited and evaluated for specific IgM/IgG antibody levels against
T. gondii
. A structured questionnaire was applied to determine the socioeconomic, environmental, gestational, clinical, and dietary patterns.
Results
The prevalence of
T. gondii
was 45.8% (n = 60) in which multiparas revealed to be more exposed to infection and were 2.6 times more likely to become infected with the parasite compared to primiparas, (odds ratio, OR=2.60; 95% confidence interval, CI=1.25-5.39). A high prevalence of
T. gondii
seropositivity was found to be related to the absence of basic sanitation at home. In conclusion, multiparas constitute risk factor for CT.
Conclusions
Educational and preventive measures should be intensified in uninfected multiparas to raise awareness about the potential risks of contact with
T. gondii
.
New safe and effective treatments for Chagas disease (CD) are urgently needed. Current chemotherapy options for CD have significant limitations, including failure to uniformly achieve parasitological ...cure or prevent the chronic phase of CD, and safety and tolerability concerns. Fexinidazole, a 2-subsituted 5-nitroimidazole drug candidate rediscovered following extensive compound mining by the Drugs for Neglected Diseases initiative and currently in Phase I clinical study for the treatment of human African trypanosomiasis, was evaluated in experimental models of acute and chronic CD caused by different strains of Trypanosoma cruzi.
We investigated the in vivo activity of fexinidazole against T. cruzi, using mice as hosts. The T. cruzi strains used in the study were previously characterized in murine models as susceptible (CL strain), partially resistant (Y strain), and resistant (Colombian and VL-10 strains) to the drugs currently in clinical use, benznidazole and nifurtimox. Our results demonstrated that fexinidazole was effective in suppressing parasitemia and preventing death in infected animals for all strains tested. In addition, assessment of definitive parasite clearance (cure) through parasitological, PCR, and serological methods showed cure rates of 80.0% against CL and Y strains, 88.9% against VL-10 strain, and 77.8% against Colombian strain among animals treated during acute phase, and 70% (VL-10 strain) in those treated in chronic phase. Benznidazole had a similar effect against susceptible and partially resistant T. cruzi strains. Fexinidazole treatment was also shown to reduce myocarditis in all animals infected with VL-10 or Colombian resistant T. cruzi strains, although parasite eradication was not achieved in all treated animals at the tested doses.
Fexinidazole is an effective oral treatment of acute and chronic experimental CD caused by benznidazole-susceptible, partially resistant, and resistant T. cruzi. These findings illustrate the potential of fexinidazole as a drug candidate for the treatment of human CD.
The formaldehyde (FA) is a crosslinking agent that reacts with cellular macromolecules such as proteins, nucleic acids and molecules with low molecular weight such as amino acids, and it has been ...linked to inflammatory processes and oxidative stress. This study aimed to analyze the oxidative effects on pulmonary inflammatory response in Fischer rats exposed to different concentrations of FA. Twenty-eight Fischer rats were divided into 4 groups (N = 7). The control group (CG) was exposed to ambient air and three groups were exposed to different concentrations of FA: 1% (FA1%), 5% (FA5%) and 10% (FA10%). In the Bronchoalveolar Lavage Fluid (BALF), the exposure to a concentration of 10% promoted the increase of inflammatory cells compared to CG. There was also an increase of macrophages and lymphocytes in FA10% and lymphocytes in FA5% compared to CG. The activity of NADPH oxidase in the blood had been higher in FA5% and FA10% compared to CG. The activity of superoxide dismutase enzyme (SOD) had an increase in FA5% and the activity of the catalase enzyme (CAT) showed an increase in FA1% compared to CG. As for the glutathione system, there was an increase in total glutathione (tGSH), reduced glutathione (GSH) and oxidized glutathione (GSSG) in FA5% compared to CG. The reduced/oxidized glutathione ratio (GSH/GSSG) had a decrease in FA5% compared to CG. There was an increase in lipid peroxidation compared to all groups and the protein carbonyl formation in FA10% compared to CG. We also observed an increase in CCL2 and CCL5 chemokines in the treatment groups compared to CG and in serum there was an increase in CCL2, CCL3 and CCL5 compared to CG. Our results point out to the potential of formaldehyde in promoting airway injury by increasing the inflammatory process as well as by the redox imbalance.
•Biochemical and histological changes are produced in the pulmonary parenchyma.•Our results point out to the potential of formaldehyde in promoting airway injury.•The effects of the exposure to FA are mediated by the production of ROS.•The effects caused by formaldehyde occurred in a dose-dependent manner.
Endogenous nucleotides produced by various group of cells under inflammatory conditions act as potential danger signals
. Extracellularly released nucleotides such as ATP are rapidly hydrolyzed to ...adenosine by the coordinated ectonucleotidase activities of CD39 and CD73.
is an obligate intracellular parasite of macrophages and capable of modulating host immune response in order to survive and multiply within host cells. In this study, the activity of CD73 induced by
in infected macrophages has been investigated and correlated with parasite survival and infection
. For this, the expression of CD39 and CD73, by flow cytometry, in murine peritoneal macrophages infected with metacyclic promastigotes of
has been analyzed. Our results showed that
infected macrophages, unlike LPS-treated macrophages, increased CD73 expression. It was also noted that when CD73 enzymatic activity was blocked by
,
-methyleneadenosine 5'-diphosphate sodium salt (APCP), macrophage parasitism was significantly decreased. Interestingly, these effects were not associated with the production of TNF-
, IL-10, or nitric oxide (NO). Together, these data demonstrate that
induces a regulatory phenotype in macrophages, which by activating the CD39/CD73 pathway allows parasite survival through the action of immunomodulatory adenosine receptors.
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