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Background. Uric acid presents different roles in an organism. High serum uric acid concentrations may induce inflammatory pathways and promote kidney damage through different mechanisms. Therefore, this study investigated the association among high serum uric acid concentrations, renal tubular damage, and renal inflammation assessed via estimation of urinary kidney injury molecule-1 (KIM-1) and inflammatory cytokines in patients with type 2 diabetes (T2D). Methods. Urinary concentrations of KIM-1, IL-1, IL-6, IL-10, and TNF-alpha, as well as other biochemical parameters, were assessed in 125 patients with T2D who were grouped into two groups based on the serum uric acid levels (Results. Urinary KIM-1, IL-1, IL-6, and TNF-alpha were higher in patients with serum uric acid concentrations≥6.0 mg/dL. However, the differences between the groups were not statistically significant when the urinary values of KIM-1 and cytokines were normalized by the urinary creatinine concentration. Serum uric acid concentrations were significantly associated with urinary KIM-1 (values normalized by urinary creatinine concentration) and urinary TNF-alpha (absolute values and values normalized by urinary creatinine concentration), independent of the body mass index (BMI) and estimated glomerular filtration rate (eGFR). Conclusions. High serum uric acid concentrations were associated with high urinary KIM-1 levels accompanied by the increase of urinary proinflammatory cytokines in patients with T2D. However, normalization of urinary markers by urine creatinine concentration seems to influence the profile of the results.

Lady Serrano Mujica,1 Alessandra Bridi,1,2 Ricardo Della Méa,1 Vitor Braga Rissi,1 Naiara Guarda,3 Rafael Noal Moresco,3 Melissa Orlandin Premaor,4 Alfredo Quites Antoniazzi,1 Paulo Bayard Dias Gonçalves,1 Fabio Vasconcellos Comim1,4 1Laboratory of Biotechnology and Animal Reproduction, BioRep, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, 2Department of Veterinary Medicine, University of São Paulo, São Paulo, 3Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, 4Department of Clinical Medicine, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil Background: Several studies have described an enhanced inflammatory status and oxidative stress balance disruption in women with polycystic ovary syndrome (PCOS). However, there is scarce information about redox markers in the blood of androgenized animal models. Here, we evaluated the serum/plasma oxidative stress marker and metabolic parameter characteristics of prenatal (PreN) and postnatal (PostN) androgenized rat models of PCOS. Materials and methods: For PreN androgenization (n=8), 2.5mg of testosterone propionate was subcutaneously administered to dams at embryonic days 16, 17, and 18, whereas PostN androgenization (n=7) was accomplished by subcutaneously injecting 1.25mg of testosterone propionate to animals at PostN day 5. A unique control group (n=8) was constituted for comparison. Results: Our results indicate that PostN group rats exhibited particular modifications in the oxidative stress marker, an increased plasma ferric-reducing ability of plasma, and an increased antioxidant capacity reflected by higher albumin serum levels. PostN animals also presented increased total cholesterol and triglyceride–glucose levels, suggesting severe metabolic disarrangement. Conclusion: Study findings indicate that changes in oxidative stress could be promoted by testosterone propionate exposure after birth, which is likely associated with anovulation and/or lipid disarrangement. Keywords: animal models of PCOS, oxidative stress, prenatal, postnatal

Oxidative stress has been recognized as a conjoint pathological mechanism that contributes to initiation and progression of liver injury, such as that caused by bacterial diseases. Natural antioxidants are considered a rational curative strategy to prevent and cure hepatic diseases involved with oxidative stress. Thus, the aim of this study was to evaluate, for the first time, whether treatment with bactericidal Melaleuca alternifolia essential oil (TTO) nanoparticles prevents or reduces the hepatic damage in silver catfish (Rhamdia quelen) experimentally infected with Pseudomonas aeruginosa (PAO1). Liver samples from fish infected with P. aeruginosa showed increased thiobarbituric acid reactive substances (TBARS), protein carbonylation and advanced oxidation protein product (AOPP) levels, while catalase (CAT) activity was reduced compared to uninfected animals. The prophylactic treatment with nanoencapsulated TTO prevented these alterations. Based on this evidence, we concluded that P. aeruginosa infection causes hepatic damage, evidenced by increased TBARS, protein carbonylation and AOPP levels, which inhibits the antioxidant defense system, contributing to disease pathophysiology. Thus, this treatment may be considered an important approach for the prevention of hepatic oxidative damage caused by P. aeruginosa infection in fish.

Appropriate control of immune responses is a critical determinant of fish health. The cholinergic and adenosinergic systems have important roles in the immune response, since acetylcholine (ACh) and adenosine (Ado) possess important anti-inflammatory properties and modulate the immune response during infectious diseases. Thus, the aim of this study was to evaluate whether splenic and lymphocytic adenosinergic and cholinergic systems are able to modulate the immune response during Pseudomonas aeruginosa infection. Acetylcholinesterase (AChE) and adenosine deaminase (ADA) activities in spleen tissue and splenic lymphocytes increased in infected animals compared to uninfected animals. Moreover, plasmatic and splenic metabolites of nitric oxide (NOx) increased in infected animals compared to uninfected animals. Therefore, our results support the hypothesis that the cholinergic and adenosinergic systems are not able to modulate the immune response against P. aeruginosa. In summary, increased AChE and ADA activities exert a pro-inflammatory profile, impairing the immune system and contributing to inflammatory damage.

Background This study investigated the association between urinary levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) with estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (uACR), and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in patients with type 2 diabetes (T2D). Methods Urinary concentrations of IL-6, IL-10, TNF-α, ACR, and NGAL were measured in 121 patients with T2D. Results Urinary IL-6 and TNF-α increased 45.5% and 49.4% in the highest uACR quartile compared to lowest quartile. Urinary IL-10 levels decreased 40.9% in the highest uACR quartile compared to the lowest quartile. Urinary IL-6 and TNF-α were 75.3% and 81.6%, higher in the highest uNGAL quartile compared to the lowest quartile. Urinary IL-10 concentration was 69.8% lower in patients from the highest uNGAL quartile compared to lowest quartile. Conclusions Urinary IL-6, IL-10, and TNF-α were associated with indicators of glomerular and tubular injuries in patients with T2D.

The aim of this study was to evaluate whether the treatment with Achyrocline satureioides essential oil-loaded in nanocapsules (AS-NC) is able to protect the hepatic tissue against cytotoxic damage caused by Trypanosoma evansi. Thus, the rats were divided into four groups (n = 6 per group): uninfected/saline, uninfected/AS-NC, infected/saline, and infected/AS-NC. At day 4 post-infection (PI), the animals were euthanized and liver and sera samples were collected to perform the hepatic cell viability assay, and to determine seric levels of reactive oxygen species (ROS) and nitric oxide metabolites (NOx). Cell viability decreased (p < 0.05) in the infected/saline group compared to uninfected/saline group, while the treatment with AS-NC avoided this alteration in infected rats. Seric ROS and NOx levels increased (p < 0.05) in the infected/saline group compared to uninfected/saline group, while the treatment with AS-NC avoided this effect on ROS levels of infected rats. In summary, the treatment with AS-NC was able to protect the liver tissue against the cytotoxic effect caused by the parasite by avoiding exacerbated production of ROS.

Although Eurytrema coelomaticum is considered a parasite with low pathogenicity, it may be associated with mortality and loss of productive performance in animals due to chronic pancreatitis. The aim of this study was to evaluate the occurrence of oxidative stress caused by E. coelomaticum in naturally infected cattle, correlating the biochemical findings with the parasite load and histopathological changes. For this study, blood and pancreas samples from 51 cattle were collected, and levels of the thiobarbituric acid reactive substances (TBARS), advanced oxidation protein products (AOPP) and ferric reducing ability of plasma (FRAP) were measured in the serum and pancreas, and superoxide dismutase (SOD) activity was measured in total blood. Parasite burden was determined opening the pancreatic ducts, and then fragments of pancreas were collected and fixed in 10% buffered formalin and routinely processed for histopathology. From the 51 collected pancreas, 33 (63.5%) were parasitized. The average parasite burden per pancreas was 532 (12-2,578). TBARS and FRAP showed higher levels in serum and pancreas of infected animals (p

This study aimed to investigate the synergistic effects of resveratrol and sulfamethoxazole-trimethoprim (ST) on the treatment of mice experimentally infected by Toxoplasma gondii during the chronic phase of the disease considering infection, behavior, and oxidative/antioxidants profile aspects. For the study, 60 mice were initially divided into two groups: uninfected (n = 24) and infected by T. gondii (n = 36). These two groups were later subdivided into other groups and treated with resveratrol (free and inclusion complex containing resveratrol) alone and co-administered with ST: groups A to D were composed by healthy mice and groups E to J were consisted of animals infected by T. gondii (VEG strain). Treatments began 20 days post-infection for 10 consecutive days with oral doses of 0.5 mg kg −1 of ST (groups B and F), 100 mg kg −1 of free resveratrol (groups C and G) and inclusion complex of resveratrol (nanoparticles containing resveratrol) (groups D and H), and lastly an co-administration of both drugs (groups I and J). Behavioral tests (memory, anxiety and locomotion) were performed after treatment. Liver and brain fragments were collected to evaluate pathological changes, brain cysts counts, as well as oxidant and antioxidant levels. A reduction on the number of cysts in the brain of animals treated with both drugs combined was observed; there was also reduced number of lesions on both organs. This drug combined effect was also able to reduce oxidative and increase antioxidant levels in infected mice, which might be interpreted as a resveratrol protective effect. In addition, the combination of ST and resveratrol was able to prevent behavioral changes in infected mice. Therefore, the use of co-administration drugs enhances the therapeutic effect acting on a synergic way, reducing the oxidizing effects of the chemical treatment for toxoplasmosis. In addition, resveratrol in inclusion complex when co-administered with ST showed an improved therapeutic effect of ST reducing oxidative damage, liver damage and the number of cysts in the brain of T. gondii infected mice.

We evaluated the influence of nanoencapsulation of the flavonoid Dihydromyricetin (DMY) in reducing the genotoxicity and cytotoxicity induced by cationic nanocapsules. Assays were conducted in order to evaluate the potential of protein corona formation, cytotoxicity, genotoxicity and the antioxidant capacity. Nanocapsules containing DMY (NC-DMY) and free DMY (DMY-F) did not demonstrate cytotoxicity and genotoxicity. However, Eudragit RS100® nanocapsules (NC-E) increased cytotoxicity and DNA damage formation. NC-DMY and NC-E presented high interaction with the DNA in vitro, suggesting DNA sequestration. These results indicate that nanoencapsulated DMY does not induce cytotoxicity or genotoxicity, and demonstrates high antioxidant capacity. This antioxidant capacity is probably associated with DMY, and occurs due to its ability to avoid the formation of free radicals, thus preventing the toxicity caused by the nanostructure with the cationic polymer Eudragit RS100®. Therefore, NC-DMY can be considered an important formulation with significant antioxidant potential to be exploited by nanomedicine.

Background The effects of adding moderate-to-high intensity inspiratory muscle training (IMT) to short-term aerobic and resistance exercise (combined training [CT]), after coronary artery bypass grafting (CABG) are not established. This study aimed to determine the effects of moderate-to-high intensity IMT + CT on exercise capacity, respiratory muscle strength, inspiratory muscle endurance, quality of life (QoL), and laboratory biomarkers in patients after CABG who were participants of a phase II cardiac rehabilitation program. Methods Twenty-four patients were randomly assigned to either the IMT + CT group (n = 12), who performed moderate-to-high intensity IMT with CT or the sham-IMT + CT group (n = 12). Patients completed two sessions per week for 12 weeks. Each patient underwent a cardiopulmonary exercise test, six-minute walk test (6MWT), respiratory muscle strength and endurance evaluation, QoL questionnaire, and serum advanced oxidation protein products, ferric reducing antioxidant power [FRAP], nitrate/nitrate, and high-sensitivity C-reactive protein, before and after the 12-week intervention. Results The IMT + CT group showed significantly greater improvements in peak oxygen uptake (1.3 mL∙kg−1∙min−1; 95% confidence interval [95% CI], 0.5 to 2.2), distance covered during the 6MWT (78.8 m; 95% CI, 28.1 to 129.5), maximal inspiratory pressure (23.0 cmH2O; 95% CI, 9.3 to 36.7), QoL (−15.1 points; 95% CI, −26.9 to −3.3), and FRAP (83.7 μmol/L; 95% CI, 20.2 to 147.1) compared to the sham-IMT + CT group as a result of the intervention. Conclusions Short-term moderate-to-high intensity IMT with CT provided additional benefits in exercise capacity, inspiratory muscle strength, QoL, and antioxidant profile in patients after CABG. Trial Registration clinicaltrials.gov Identifier: NCT02885077

The aim of this study was to evaluate whether the addition of curcumin in the diet of commercial laying hens could have an anticoccidial action and improve egg quality. For this, 60 laying hens were divided into three groups: T0 (the control group); T30 and T50 (30 and 50 mg/kg of curcumin in the feed, respectively). Eggs recently laid were collected on days 14 and 21 of the experiment, and stored for 21 days. It was observed increased specific gravity and yolk index in stored eggs of the groups T30 and T50 compared to T0. The yolk color reduced in the eggs stored from groups T30 and T50 compared to T0. Moreover, TBARS levels were lower in fresh and stored eggs from groups T30 and T50. It was observed increased TAC levels in fresh eggs from groups T30 and T50 and in stored eggs from the group T50. The presence of curcumin was not detected by HPLC in the yolk and albumen. Seric levels of albumin and uric acid did not differ between groups, while seric levels of total proteins increased on day 21 on groups T30 and T50. Finally, it was observed a significant reduction on the number of oocysts in fecal samples on days 14 and 21 of T30 and T50 compared to T0. Based on these evidences, it is possible to conclude that the addition of curcumin in the diet of laying hens has an anticoccidial effect and improves egg quality.

The aim of this study was to analyses nitric oxide, antioxidant status, and oxidative profile in the liver of laying hens naturally infected by Salmonella enterica subsp enterica serovar Gallinarum (S. Gallinarum). The nitrite/nitrate (NOx), reactive oxygen species (ROS), thiobarbituric acid-reactive substances (TBARS), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were measured in liver samples, as well the biomarkers of hepatic function (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), total protein and albumin levels measured in serum. NOx levels and CAT activity were reduced in hepatic tissue of infected hens. On the other hand, TBARS and ROS levels, GR, GPx and GST activities were higher in infected animals. On biomarkers of tissue damage, ALT, AST, GGT and total protein levels were higher in serum of infected hens, and showed decreased albumin levels. In summary, ROS and TBARS production lead to damage on the membrane lipids that alter activities of antioxidant enzymes CAT, GR, GPx and GSH, an adaptive response against S. Gallinarum infection, contributing to the pathophysiology and clinical signs of the disease.

BACKGROUND Red blood cell indices may add important prognostic information to risk stratification scores, such as Global Registry of Acute Coronary Events (GRACE) risk score. However, the incremental predictive value of red blood cell distribution width (RDW) on this score has not been assessed. Therefore, the aim of this study was to assess whether the RDW has additional prognostic value on the GRACE risk score in prediction of in-hospital mortality in patients with acute myocardial infarction (AMI). METHODS A historic cohort was investigated at the University Hospital in Santa Maria city, Brazil. The laboratory database and medical registry were used to identify patients with AMI. A total of 109 patients were eligible for the present study. Cox regression models were calculated including GRACE risk score variables plus RDW. Moreover, measures of discrimination and calibration were also calculated. The primary outcome evaluated was all-cause in-hospital mortality. RESULTS When included in a predictive model based on the GRACE risk score, RDW became an independent predictor of in-hospital mortality (HR 1.358, 95% CI 1.04 - 1.77; p = 0.023). The addition of RDW to the original model showed adequate calibration (Hosmer-Lemeshow p-value 0.174) and produced a slight improvement in its discriminatory power (AUC 0.769, 95% CI 0.677 - 0.847; p = < 0.0001). CONCLUSIONS We suggest that RDW might provide additional information over the GRACE risk score in patients with AMI.

The aim of this study was to assess the effects of iron supplementation on oxidative stress and on the activity of the adenosine deaminase (ADA) in rats experimentally infected by Trypanosoma evansi. For this purpose, 20 rats were divided into four experimental groups with five animals each as follows: groups A and B were composed by healthy animals, while animals from groups C and D were infected by T. evansi. Additionally, groups B and D received two subcutaneous doses of iron (60 mg kg-1) within an interval of 5 days. Blood samples were drawn on day 8 post infection in order to assess hematological and biochemical variables. Among the main results are: (1) animals from group C showed reduced erythrogram (with tendency to anemia); however the same results were not observed for group D; this might be a direct effect of free iron on trypanosomes which helped to reduce the parasitemia and the damage to erythrocytes caused by the infection; (2) iron supplementation was able to reduce NOx levels by inhibiting iNOS, and thus, providing an antioxidant action and, indirectly, reducing the ALT levels in groups Band D; (3) increase FRAP levels in group D; (4) reduce ADA activity in serum and erythrocytes in group C; however, this supplementation (5) increased the protein oxidation in groups B and D, as well as group C (positive control). Therefore, iron showed antioxidant and oxidant effects on animals that received supplementation; and it maintained the activity of E-ADA stable in infected/supplemented animals.