Long-term e-cigarette aerosol exposure causes pulmonary emphysema in adult female and male mice.

This study aimed to evaluate long-term exposure to conventional cigarette smoke (CC) and electronic cigarette (EC) aerosol in adult male and female C57BL/6 mice. Forty-eight C57BL/6 mice were used, male (n = 24) and female (n = 24), both were divided into three groups: control, CC and EC. The CC and EC groups were exposed to cigarette smoke or electronic cigarette aerosol, respectively, 3 times a day for 60 consecutive days. Afterwards, they were maintained for 60 days without exposure to cigarettes or electronic cigarette aerosol. Both cigarettes promoted an influx of inflammatory cells to the lung in males and females. All animals exposed to CC and EC showed an increase in lipid peroxidation and protein oxidation. There was an increase of IL-6 in males and females exposed to EC. The IL-13 levels were higher in the females exposed to EC and CC. Both sexes exposed to EC and CC presented tissue damage characterized by septal destruction and increased alveolar spaces compared to control. Our results demonstrated that exposure to CC and EC induced pulmonary emphysema in both sexes, and females seem to be more susceptible to EC.

Temporal analysis of paracetamol-induced hepatotoxicity.

Paracetamol-induced hepatotoxicity (APAP) causes severe damage that may be irreversible. Understanding the evolution of liver injury caused by overdose of the drug is important to assist in the treatment. In the present study, we evaluated the acute intoxication by APAP (500 mg/kg) in periods of 3 and 12 hours in C57BL/6 mice through biochemical, histological, inflammatory parameters, and the redox status. The results showed that in the 3-hour period there was an increase in creatinine dosage and lipid peroxidation (TBARS) compared to the control group. In the period of 12 hours after APAP intoxication all parameters evaluated were altered; there was an increase of ALT, AST, and necrosis, besides the increase of redox status biomarkers as carbonylated protein, TBARS, and MMP-9. We also observed activation of the inflammasome pathway as well as a reduction in the regenerative capacity of hepatocytes with a decrease in binucleated liver cells. In cytochrome gene expression, the mRNA level increased in CYP2E1 isoenzyme and reduced CYP1A2 expression. This study indicated that early treatment is necessary to mitigate APAP-induced acute liver injury, and alternative therapies capable of controlling the progression of intoxication in the liver are needed.

Trypanosoma cruzi infection increases atherosclerotic lesion in ApoE-deficient mice.

Apolipoprotein E (ApoE) is the major ligand for the transporting and removal of chylomicrons and lipoproteins by the liver. Since the creation of the ApoE-knockout mice, it is well established that ApoE deficiency results in spontaneous atherosclerosis in aged animals. Atherosclerosis is also observed in animals infected with Trypanosoma cruzi, a protozoan that elicits a systemic inflammatory response in mammalian hosts, culminating in damage to cardiac, neuronal, and endothelial cells. Pro-atherogenic effects related to the experimental infection with T. cruzi may be induced by inflammatory components affecting the vascular wall. Herein, we evaluated whether infection with different strains of T. cruzi worsened the atherogenic lesions observed in aged ApoE-/- mice. After four weeks of infection with Berenice-78 (Be-78) or Colombian (Col) strains of the parasite, mice presented increased CCL2 and CCL5 production and high migration of inflammatory cells to cardiac tissue. Although the infection with either strain did not affect the survival rate, only the infection with Col strain caused abundant parasite growth in blood and heart and increased aortic root lesions in ApoE-/- mice. Our findings show, for the first time that ApoE exerts a protective anti-atherosclerotic role in the aortic root of mice in the acute phase of experimental infection with the Col strain of T. cruzi. Further studies should target ApoE and nutritional interventions to modulate susceptibility to cardiovascular disabilities after T. cruzi infection, minimizing the risk of death in both experimental animals and humans.

EPA/DHA and linseed oil have different effects on liver and adipose tissue in rats fed with a high-fat diet.

The incidence of cardiovascular diseases and metabolic disorders has increased worldwide. Clinical and experimental research has shown that the consumption of ω-3 FAs can be beneficial to metabolism in several ways, as they can act on metabolic pathways. Our objective was to evaluate the effect of treatment with linseed oil, a vegetable oil rich in alpha-linolenic acid, and EPA and DHA in different proportions (3:1 EPA:DHA, and 1:3 EPA:DHA), on the metabolic disorders induced by a high-fat diet (20 % lipids) in rats for 2 weeks, after 18 weeks of consumption of a high-fat diet. In 18 weeks, the high-fat diet increased blood glucose, systolic blood pressure, triglyceride concentration in the liver and adipose tissue, and impaired insulin sensibility without interfering in the weight of the animals. All treatments were effective in reducing the deposition of hepatic type III collagen, the proportion of ω-6/ω-3 in the liver and WAT (white adipose tissue), the proportion of area/number of adipocytes, and the gene expression of the ACC, FAS, and CPT1 enzymes. In addition, treatment with EPA and DHA reduced blood glucose, serum TNF-α concentration, amount of liver fat, degree of microsteatosis and type I collagen deposition in the liver, deposition of type I and III collagen in TA, gene expression of the transcription factor SREBP-1c, and increased hepatic binucleation. EPA in major proportion was more effective in reducing the area of adipocytes, hepatic triglyceride concentration, PPAR-α expression, and WAT fat weight. DHA in a major proportion reduced the concentration of MCP1 in WAT. LO treatment did not have any isolated effects. We concluded that EPA and DHA were more effective in treating metabolic damage than treatment with LO, leading to a more favorable metabolic profile.

Prognosis of chronic Chagas heart disease and other pending clinical challenges.

In this chapter, the main prognostic markers of Chagas heart disease are addressed, with an emphasis on the most recent findings and questions, establishing the basis for a broad discussion of recommendations and new approaches to managing Chagas cardiopathy. The main biological and genetic markers and the contribution of the electrocardiogram, echocardiogram and cardiac magnetic resonance are presented. We also discuss the most recent therapeutic proposals for heart failure, thromboembolism and arrhythmias, as well as current experience in heart transplantation in patients suffering from severe Chagas cardiomyopathy. The clinical and epidemiological challenges introduced by acute Chagas disease due to oral contamination are discussed. In addition, we highlight the importance of ageing and comorbidities in influencing the outcome of chronic Chagas heart disease. Finally, we discuss the importance of public policies, the vital role of funding agencies, universities, the scientific community and health professionals, and the application of new technologies in finding solutions for better management of Chagas heart disease.

Resolvin D1 Administration Is Beneficial in Trypanosoma cruzi Infection.

Chagas disease is a major public health issue, affecting ∼10 million people worldwide. Transmitted by a protozoan named Trypanosoma cruzi, this infection triggers a chronic inflammatory process that can lead to cardiomyopathy (Chagas disease). Resolvin D1 (RvD1) is a novel proresolution lipid mediator whose effects on inflammatory diseases dampens pathological inflammatory responses and can restore tissue homeostasis. Current therapies are not effective in altering the outcome of T. cruzi infection, and as RvD1 has been evaluated as a therapeutic agent in various inflammatory diseases, we examined if exogenous RvD1 could modulate the pathogenesis of Chagas disease in a murine model. CD-1 mice infected with the T. cruzi Brazil strain were treated with RvD1. Mice were administered 3 µg/kg of body weight RvD1 intraperitoneally on days 5, 10, and 15 to examine the effect of RvD1 on acute disease or administered the same dose on days 60, 65, and 70 to examine its effects on chronic infection. RvD1 therapy increased the survival rate and controlled parasite replication in mice with acute infection and reduced the levels of interferon gamma and transforming growth factor ß (TGF-ß) in mice with chronic infection. In addition, there was an increase in interleukin-10 levels with RvD1 therapy in both mice with acute infection and mice with chronic infection and a decrease in TGF-ß levels and collagen content in cardiac tissue. Together, these data indicate that RvD1 therapy can dampen the inflammatory response, promote the resolution of T. cruzi infection, and prevent cardiac fibrosis.

Ectonucleotidases from trypomastigotes from different sources and various genetic backgrounds of Trypanosoma cruzi potentiate their infectivity and host inflammation.

Distinct populations of Trypanosoma cruzi interact with mammalian cardiac muscle cells causing different inflammation patterns and low heart functionality. During T. cruzi infection, the extracellular ATP is hydrolyzed to tri- and/or diphosphate nucleotides, based on the infectivity, virulence, and regulation of the inflammatory response. T. cruzi carries out this hydrolysis through the T. cruzi ectonucleotidase, NTPDase-1 (TcNTPDase-1). This study aimed to evaluate the role of TcNTPDase-1 in culture rich in metacyclic trypomastigote forms (MT) and cell culture-derived trypomastigote forms (CT) from Colombiana (discrete typing unit - DTU I), VL-10 (DTU II), and CL (DTU VI) strains of T. cruzi. For this, we measured TcNTPDase-1 activity in suramin-treated and untreated parasites and infected J774 cells and C57BL/6 mice with suramin pre-treated parasites to assess parasitic and inflammatory cardiac profile in the acute phase of infection. Our data indicated a higher TcNTPDase-1 activity for ATP in culture rich in metacyclic trypomastigote forms from Colombiana strain in comparison to those from VL-10 and CL strains. The cell culture-derived trypomastigote forms from CL strain presented higher capacity to hydrolyze ATP than those from Colombiana and VL-10 strains. Suramin inhibited ATP hydrolysis in all studied parasite forms and strains. Suramin pre-treated parasites reduced J774 cell infection and increased nitrite production in vitro. In vivo studies showed a reduction of inflammatory infiltrate in the cardiac tissues of animals infected with cell culture-derived trypomastigote forms from suramin pre-treated Colombiana strain. In conclusion, TcNTPDase-1 activity in trypomastigotes forms drives part of the biological characteristics observed in distinct DTUs and may induce cardiac pathogenesis during T. cruzi infection.

Aluminum hydroxide nebulization-induced redox imbalance and acute lung inflammation in mice.

Purpose: Aluminum is the third most abundant metal in the earth's crust and is widely used in industry. Chronic contact with aluminum results in a reduction in the activity of electron transport chain complexes, leading to excessive production of reactive oxygen species (ROS) and oxidative stress. This study aimed to evaluate the effects of short-term exposure of aluminum hydroxide on oxidative stress and pulmonary inflammatory response.Materials and methods: Male BALB/c mice were divided into three groups: control group (CG); phosphate buffered saline group (PBSG) and aluminum hydroxide group (AHG). CG was exposed to ambient air, while PBSG and AHG were exposed to PBS or aluminum hydroxide solutions via nebulization, three times per day for five consecutive days. Twenty-four hours after the last exposure, all animals were euthanized for subsequent analysis.Results: Exposure to aluminum hydroxide in the blood resulted in lower platelet levels, higher neutrophils, and lower monocytes compared to CG and PBSG. Aluminum hydroxide promoted the recruitment of inflammatory cells to the lung. Macrophage, neutrophil and lymphocyte counts were higher in AHG compared to CG and PBSG. Protein oxidation and superoxide dismutase activity were higher, while catalase activity and reduced and oxidizes glutathione ratio in AHG were lower compared to CG and PBSG. Furthermore, there was an increase in the inflammatory markers CCL2 and IFN-γ in AHG compared to CG and PBSG.Conclusion: In conclusion, short-term nebulization with aluminum hydroxide induces the influx of inflammatory cells and oxidative stress in adult BALB/c mice.

Inflammatory and oxidative stress biomarkers induced by silica exposure in crystal craftsmen.

BACKGROUND: Identification of biomarkers associated with the diagnosis and prognosis of silicosis would be highly advantageous in the clinical setting. The aim of this study is to evaluate inflammatory and oxidative stress biomarkers in subjects exposed to silica. METHODS: A cross-sectional study of crystal craftsmen currently (n = 34) or formerly (n = 35) exposed and a group of nonexposed subjects (n = 12) was performed. Personal respirable dust samples were collected. Plasma inflammatory mediators (bone morphogenetic protein- BMP2 and chemokines CXCL16, and CCL5), oxidative stress enzymes (thiobarbituric acid reactive substances [TBARs] and superoxide dismutase [SOD]), and nitrite (NO2- ) were analyzed in parallel with nitric oxide in exhaled breath (FeNO). RESULTS: Being currently or formerly exposed to silica was related to increased levels of CXCL16 and TBARs. Currently, exposed subjects showed decreased levels of SOD. Thirty-seven craftsmen with silicosis (26 formerly and 11 currently exposed) showed higher levels of CXCL16, which was positively associated with the radiological severity of silicosis. Compared with the nonexposed, subjects with silicosis had higher levels of TBARs and those with complicated silicosis had lower levels of SOD. In multivariate analysis, higher levels of CXCL16 were associated with exposure status and radiological severity of silicosis. Smoking was not a confounder. FeNO did not distinguish between the exposure status and the presence of silicosis. CONCLUSION: CXCL16 emerged as a potential biomarker that could distinguish both silica exposure and silicosis. TBARs were elevated in exposed individuals. However, their clinical applications demand further investigation in follow-up studies of representative samples.

IL-33 in obesity: where do we go from here?

IL-33 is a cytokine that belongs to the IL-1 family and is classically associated with type 2-like immune responses. In the adipose tissue, IL-33 is related to the beiging of adipocytes and to the maintenance of adipose tissue-resident immune cells, such as innate lymphoid cells 2, alternatively activated macrophages and regulatory T cells, which contribute to the maintenance of adipose tissue homeostasis. In the obese adipose tissue, the number of these cells is diminished, unlike the expression of IL-33, which is up-regulated. However, despite its increased expression, IL-33 is not able to maintain the homeostasis of the obese adipose tissue. IL-33 treatment, on the other hand, highly improves obesity-related inflammatory and metabolic alterations. The evidence that exogenous IL-33, but not adipose tissue-driven IL-33, regulates the inflammatory process in obesity leaves a gap in the understanding of IL-33 biology. Thus, in this review we discuss the potential mechanisms associated with the impaired action of IL-33 in obesity.

Association among ACE, ESR1 polymorphisms and preeclampsia in Brazilian pregnant women.

BACKGROUND: Genetic, immune and environmental factors are involved in preeclampsia (PE) etiopathogenesis. Considering that hypertension and poor placental perfusion are important features in PE, polymorphisms in the angiotensin-converting enzyme (ACE) and estrogen nuclear receptor 1 (ESR1) genes could be involved in the predisposition and/or development of the disease. The aim of this study was to evaluate if polymorphisms in ACE and ESR1 genes were associated with PE occurrence. MATERIAL AND METHODS: This case-control study included 209 Brazilian pregnant women (107 with severe PE and 102 normotensive controls). The polymorphisms were investigated by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis. RESULTS: No significant difference between PE versus normotensive pregnant women, as well as early versus late PE, was observed when compared the allelic and genotypic frequencies of insertion/deletion polymorphism in intron 16 of the ACE gene and the single nucleotide polymorphisms (SNPs - rs2234693 and rs9340799) of the ESR1 gene. CONCLUSION: This pioneer study involving Brazilian women showed no association among the studied polymorphisms and PE, which suggests that ins/del ACE and SNPs ESR1 do not contribute to this disease occurrence in Brazil.

Could pre-infection exercise training improve the efficacy of specific antiparasitic chemotherapy for Chagas disease?

Considering a potential exercise-drug interaction, we investigated whether exercise training could improve the efficacy of specific antiparasitic chemotherapy in a rodent model of Chagas disease. Wistar rats were randomized into five groups: sedentary and uninfected (CT); sedentary and infected (SI); sedentary, infected and treated (SIT); trained and infected (TI); trained, infected and treated (TIT). After 9-weeks running training, the animals were infected with T. cruzi and followed up for 4 weeks, receiving 100 mg kg-1 day-1 benznidazole. No evidence of myocarditis was observed in CT animals. TI animals exhibited reduced parasitemia, myocarditis, and reactive tissue damage compared to SI animals, in addition to increased IFN-γ, IL-4, IL-10, heart non-protein antioxidant (NPA) levels and glutathione-s transferase activity (P < 0.05). The CT, SIT and TIT groups presented similar reductions in parasitemia, cytokines (IFN-γ, TNF-α, IL-4, IL-10, IL-17 and MCP-1), inflammatory infiltrate, oxidative heart damage and antioxidant enzymes activity compared to SI and TI animals, as well as reduced heart microstructural remodeling (P < 0.05). By modulating heart inflammation and redox metabolism, exercise training exerts a protective effect against T. cruzi infection in rats. However, the antiparasitic and cardioprotective effects of benznidazole chemotherapy are more pronounced, determining similar endpoints in sedentary and trained T. cruzi-infected rats.

The overweight increases circulating inflammatory mediators commonly associated with obesity in young individuals.

Obesity is a serious and growing world healthy problem affecting developed and developing countries. The new conception of obesity as a basal inflammatory condition has opened a new window of possibilities to identify inflammatory biomarkers to be used in the diagnosis or prognosis of obesity-associated comorbidities. This present work aims the identification of the adipokines (leptin and resistin), chemokines (CCL2, CCL5, CXCL16) and the BMP-2 and their association with the clinical, biochemical (fasting glucose, hemogram, cholesterol, T3, T4 and TSH) and anthropometric (weight, height, body circumferences, skinfold thickness and percentage of body fat) parameters in young adults (18-30 years old) presenting obesity and overweight. Our data showed increasing in anthropometric parameters and in the plasma inflammatory levels in those individuals presenting overweight and obesity. We observed a higher plasma levels of CCL2, CCL5, CXCL16, leptin and resistin in those overweigh and obese individuals. In addition, the CCL2, CCL5 presented a positive correlation with the body mass index and the body fat percentage. Assuming the obesity as a systemic inflammatory process, in this current study, the overweight individuals possess a close similar pattern of circulating inflammatory mediators which might be a potential risk of the development of obesity comorbidities. Further studies are still needed to precise the role of the biomarkers CCL2, CCL5, CXCL16 and BMP-2 in the clinical prognosis related to the overweight or obese individuals.

IL-10 and TGF-ß unbalanced levels in neutrophils contribute to increase inflammatory cytokine expression in childhood obesity.

PURPOSE: Obesity is a multifactorial disease, associated with metabolic disorders, chronic low-grade inflammation, and impaired immunity. This study aimed to evaluate the childhood obesity-associated effects on neutrophil activation and cytokine production. METHODS: We evaluated activation and recognition markers and cytokine production in neutrophils from the peripheral blood of children with obesity and normal weight using multicolor flow cytometry. RESULTS: We demonstrate a higher frequency of neutrophils in childhood obesity group (CO) compared to normal-weight group (NW). Our data showed that neutrophils from CO group are capable of antigen recognition and presentation through higher expression of TLR-4 (CD284) and HLA-DR in comparison with neutrophils from NW. On the other hand, neutrophils from CO group are faulty to deliver co-stimulatory signals, through lower expression of co-stimulatory molecules. We showed an increased expression of IL-6, IL-1ß, IL-12, and TNF, and decreased expression of IL-8 and IL-10 by neutrophils from CO compared to NW, while TGF-ß is equivalently expressed in neutrophils from both groups. Despite this, we observed that TGF-ß/inflammatory cytokine ratio was significantly higher than the IL-10/inflammatory cytokine ratio only in CO group. Our analysis showed obesity altering the correlation profile for the expression of co-stimulatory, recognition, and activation molecules, as well as for cytokines by neutrophils, suggesting an association between lower IL-10 expression and inflammation in childhood obesity. CONCLUSIONS: The unbalance between the ratio of IL-10 and TGF-ß expressions, the IL-10 lower expression, and changes in correlation profile seem to contribute with an inefficient regulation of inflammatory cytokine expression in childhood obesity. However, these changes still not may be considered the sole mechanism that directs inflammation during childhood obesity, once other molecules, pathways, and cells should be evaluated.

Taurine treatment decreases inflammation and oxidative stress in lungs of adult mice exposed to cigarette smoke.

Taurine is the major free amino acid found in mammalian cells and is known to be an antioxidant and membrane-stabilizing agent. This study aimed to evaluate the effects of taurine on oxidative stress and inflammatory response in the lungs of mice exposed to cigarette smoke. Fifty male C57BL/6 mice were divided into 5 groups: control group (CG), vehicle group (VG), taurine group (TG), cigarette smoke group (CSG), and cigarette smoke + taurine group (CSTG). For five consecutive days, CSG and CSTG were exposed to 4 cigarettes 3 times a day. Taurine administration was able to reduce total leukocytes in bronchoalveolar lavage fluid in CSTG compared to CSG. There was an increase in antioxidant superoxide dismutase and catalase activity in CSG compared to that in CG and TG, and a decrease in CSTG compared to CSG. There was an increase in the concentration of TNF and IL-17 in CSG and CSTG compared to CG and TG. There was an increase in the concentration of IL-22 in CSG compared to CG and TG, and a decrease in CSTG compared to CSG. The administration of taurine has been shown to reduce the inflammation and oxidative stress induced by short-term exposure to cigarette smoke.

The ß-blocker carvedilol and the benznidazole modulate the cardiac immune response in the acute infection induced by Colombian strain of the Trypanosoma cruzi.

BACKGROUND The infection led by Trypanosoma cruzi persists in mammalian tissues causing an inflammatory imbalance. Carvedilol (Cv), a non-selective beta blocker drug indicated to treat heart failure and antihypertensive has shown to promote antioxidant and immunomodulatory properties which might improve the inflammation induced by T. cruzi. OBJECTIVES Evaluate the role of Cv on the inflammatory response of C57BL/6 mice acutely infected with the Colombian strain of T. cruzi. METHODS Animals were infected with the Colombian strain of T. cruzi and treated with Cv (25 mg/kg/day), benznidazole (Bz) (100 mg/kg/day) or their combination. On the 28th day of infection and 23 days of treatment, the euthanasia occurred, and the heart preserved for histopathological, oxidative stress (SOD, catalase, TBARs, carbonylated proteins) and plasma (CCL2, CCL5, TNF, IL-10) analyses. Parasitaemia and survival were assessed along the infection. FINDINGS Cv decreased TBARs, but increased the mortality rate, the parasitaemia and the levels of CCL2, CCL5, catalase and the inflammatory infiltrate in the cardiac tissue. Bz led the reduction of the inflammatory infiltrate and circulating levels of oxidative stress and inflammatory mediators in the infected mice. MAIN CONCLUSIONS Our data suggest that Cv, in this experimental model using the Colombian strain of T. cruzi, caused damage to the host.

Expression and production of cardiac angiogenic mediators depend on the Trypanosoma cruzi-genetic population in experimental C57BL/6 mice infection.

Mammalian cardiac cells are important targets to the protozoan Trypanosoma cruzi. The inflammatory reaction in the host aims at eliminating this parasite, can lead to cell destruction, fibrosis and hypoxia. Local hypoxia is well-defined stimulus to the production of angiogenesis mediators. Assuming that different genetic T. cruzi populations induce distinct inflammation and disease patterns, the current study aims to investigate whether the production of inflammatory and angiogenic mediators is a parasite strain-dependent condition. C57BL/6 mice were infected with the Y and Colombian strains of T. cruzi and euthanized at the 12th and 32nd days, respectively. The blood and heart tissue were processed in immune assays and/or qPCR (TNF, IL-17, IL-10, CCL2, CCL3, CCL5, CCR2, CCR5 and angiogenic factors VEGF, Ang-1, Ang-2) and in histological assays. The T. cruzi increased the inflammatory and angiogenic mediators in the infected mice when they were compared to non-infected animals. However, the Colombian strain has led to higher (i) leukocyte infiltration, (ii) cardiac TNF and CCL5 production/expression, (iii) cardiac tissue parasitism, and to higher (iv) ratio between heart/body weights. On the other hand, the Colombian strain has caused lower production and expression VEGF, Ang-1 and Ang-2, when it was compared to the Y strain of the parasite. The present study highlights that the T. cruzi-genetic population defines the pattern of angiogenic/inflammatory mediators in the heart tissue, and that it may contribute to the magnitude of the cardiac pathogenesis. Besides, such assumption opens windows to the understanding of the angiogenic mediator's role in association with the experimental T. cruzi infection.

Lycopene pretreatment improves hepatotoxicity induced by acetaminophen in C57BL/6 mice.

Acetaminophen (APAP) is an antipyretic and analgesic drug that, in high doses, leads to severe liver injury and potentially death. Oxidative stress is an important event in APAP overdose. Researchers are looking for natural antioxidants with the potential to mitigate the harmful effects of reactive oxygen species in different models. Lycopene has been widely studied for its antioxidant properties. The aim of this study was to evaluate the antioxidant potential of lycopene pretreatment in APAP-induced liver injury in C57BL/6 mice. C57BL/6 male mice were divided into the following groups: control (C); sunflower oil (CO); acetaminophen 500mg/kg (APAP); acetaminophen 500mg/kg+lycopene 10mg/kg (APAP+L10), and acetaminophen 500mg/kg+lycopene 100mg/kg (APAP+L100). Mice were pretreated with lycopene for 14 consecutive days prior to APAP overdose. Analyses of blood serum and livers were performed. Lycopene was able to improve redox imbalance, decrease thiobarbituric acid reactive species level, and increase CAT and GSH levels. In addition, it decreased the IL-1ß expression and the activity of MMP-2. This study revealed that preventive lycopene consumption in C57BL/6 mice can attenuate the effects of APAP-induced liver injury. Furthermore, by improving the redox state, and thus indicating its potential antioxidant effect, lycopene was also shown to have an influence on inflammatory events.

Nonsteroidal anti-inflammatory is more effective than anti-oxidant therapy in counteracting oxidative/nitrosative stress and heart disease in T. cruzi-infected mice.

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.

CXCL-16, IL-17, and bone morphogenetic protein 2 (BMP-2) are associated with overweight and obesity conditions in middle-aged and elderly women.

BACKGROUND: The current concept of overweight/obesity is most likely related to a combination of increased caloric intake and decreased energy expenditure. Widespread inflammation, associated with both conditions, appears to contribute to the development of some obesity-related comorbidities. Interventions that directly or indirectly target individuals at high risk of developing obesity have been largely proposed because of the increasing number of overweight/obese cases worldwide. The aim of the present study was to assess CXCL16, IL-17, and BMP-2 plasma factors in middle-aged and elderly women and relate them to an overweight or obese status. In total, 117 women were selected and grouped as eutrophic, overweight, and obese, according to anthropometric parameters. Analyses of anthropometric and circulating biochemical parameters were followed by plasma immunoassays for CXCL-16, IL-17, and BMP-2. RESULTS: Plasma mediators increased in all overweight and obese individuals, with the exception of BMP-2 in the elderly group, whereas CXCL16 levels were shown to differentiate overweight and obese individuals. Overweight and/or obese middle-aged and elderly individuals presented with high LDL, triglycerides, and glycemia levels. Anthropometric parameters indicating increased-cardiovascular risk were positively correlated with CXCL-16, BMP-2, and IL-17 levels in overweight and obese middle-aged and elderly individuals. CONCLUSION: This study provides evidence that CXCL-16, IL-17, and BMP-2 are potential plasma indicators of inflammatory status in middle-aged and elderly women; therefore, further investigation of obesity-related comorbidities is recommended. CXCL16, in particular, could be a potential marker for middle-aged and elderly individuals transitioning from eutrophic to overweight body types, which represents an asymptomatic and dangerous condition.