Increased levels of advanced oxidation protein products (AOPPs) were associated with nociceptive behavior and clinical scores in an experimental progressive autoimmune encephalomyelitis model (PMS-EAE).

Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system (CNS) generating neuropathic pain and anxiety. Primary progressive MS (PPMS) is the most disabling clinical form, and the patients present an intense neurodegenerative process. In this context, the advanced oxidation protein products (AOPPs) are oxidized compounds and their accumulation in plasma has been related to clinical disability in MS patients. However, the involvement of AOPPs in neuropathic pain- and anxiety-like symptoms was not previously evaluated. To assess this, female mice C57BL/6J were used to induce progressive experimental autoimmune encephalomyelitis (PMS-EAE). Clinical score, weight, strength of plantar pressure, rotarod test, mechanical allodynia, and cold hypersensitivity were evaluated before induction (baseline) and on days 7th, 10th, and 14th post-immunization. We assessed nest building, open field, and elevated plus-maze tests 13 days post-immunization. Animals were killed at 14 days post-immunization; then, AOPPs levels, NADPH oxidase, and myeloperoxidase (MPO) activity were measured in the prefrontal cortex, hippocampus, and spinal cord samples. The clinical score increased 14th post-immunization without changes in weight and mobility. Reduced paw strength, mechanical allodynia, and cold allodynia increased in the PMS-EAE animals. PMS-EAE mice showed spontaneous nociception and anxiety-like behavior. AOPPs concentration, NADPH oxidase, and MPO activity increase in CNS structures. Multivariate analyses indicated that the rise of AOPPs levels, NADPH oxidase, and MPO activity influenced the clinical score and cold allodynia. Thus, we indicated the association between non-stimuli painful perception, anxiety-like, and CNS oxidative damage in the PMS-EAE model.

Topical application of a TRPA1 antagonist reduced nociception and inflammation in a model of traumatic muscle injury in rats.

Musculoskeletal pain is a widely experienced public healthcare issue, especially after traumatic muscle injury. Besides, it is a common cause of disability, but this pain remains poorly managed. However, the pathophysiology of traumatic muscle injury-associated pain and inflammation has not been fully elucidated. In this regard, the transient receptor potential ankyrin 1 (TRPA1) has been studied in inflammatory and painful conditions. Thus, this study aimed to evaluate the antinociceptive and anti-inflammatory effect of the topical application of a TRPA1 antagonist in a model of traumatic muscle injury in rats. The mechanical trauma model was developed by a single blunt trauma impact on the right gastrocnemius muscle of Wistar male rats (250-350 g). The animals were divided into four groups (Sham/Vehicle; Sham/HC-030031 0.05%; Injury/Vehicle, and Injury/HC-030031 0.05%) and topically treated with a Lanette® N cream base containing a TRPA1 antagonist (HC-030031, 0.05%; 200 mg/muscle) or vehicle (Lanette® N cream base; 200 mg/muscle), which was applied at 2, 6, 12, 24, and 46 h after muscle injury. Furthermore, we evaluated the contribution of the TRPA1 channel on nociceptive, inflammatory, and oxidative parameters. The topical application of TRPA1 antagonist reduced biomarkers of muscle injury (lactate/glucose ratio), spontaneous nociception (rat grimace scale), inflammatory (inflammatory cell infiltration, cytokine levels, myeloperoxidase, and N-acetyl-ß-D-glucosaminidase activities) and oxidative (nitrite levels and dichlorofluorescein fluorescence) parameters, and mRNA Trpa1 levels in the muscle tissue. Thus, these results demonstrate that TRPA1 may be a promising anti-inflammatory and antinociceptive target in treating muscle pain after traumatic muscle injury.

Anthropometric measurements and their association with endothelial function and arterial stiffness of eutrophic individuals and with overweight.

Objective: The objective of the study was to assess the association of anthropometric measurements with endothelial function and arterial stiffness of eutrophic individuals and with overweight. Subjects and methods: A cross-sectional study was carried out with individuals with body mass index (BMI) between 18.5 kg/m2 and < 30 kg/m2, low to intermediate global cardiovascular risk scores, and aged ≥ 18 and < 60 years. We assessed the sociodemographic data, anthropometric variables (body weight, height, circumferences of the waist [WC], neck [NC], hip [HC], sagittal abdominal diameter [SAD], [BMI], waist-to-hip ratio [WHR], and waist-to-height ratio [WHtR]), biochemical parameters (lipid profile and nitric oxide), endothelial function (flow-mediated dilation [FMD], by ultrasound), and arterial stiffness (pulse wave velocity [PWV] and the amplification index [AIx@75] by oscillometry). Thirty-six individuals were included, 18 eutrophic and 18 with overweight, with a mean age of 37.5 ± 10.2 years, mostly at low cardiovascular risk (86.1%), female (80.6%), single (52.8%), employed with formal contracts (44.4%), and with over twelve years of education (88.9%). Results: The PWV presented positive and moderate correlation with the WC (r = 0.584; P = 0.001), WHR (r = 0.513; P = 0.001), and WHtR (r = 0.590; P = 0.001), and positive and low correlation with the NC (r = 0.372; P = 0.013) and SAD (r = 0.356; P = 0.033). Moreover, no anthropometric parameter presented a correlation with the AIx@75 or the FMD percentage in the total sample. Conclusion: Our findings show that in eutrophic individuals and with overweight the WC, WHR, WHtR, SAD, and NC were positively correlated with the PWV but not to the endothelial function in the overall sample. These are hypothesis-generating findings and they should be replicated in other studies.

Variation of the Oxidative Profile in Pregnant Women With and Without Gestational Complications.

INTRODUCTION: Oxidative stress is closely related to the pathophysiology of gestation, where the placenta is susceptible to oxidative damage, contributing to the onset of gestational complications. Currently, few studies evaluate the use of oxidative markers for prediction of risk of gestational complications. However, there are some reports that suggest these biomarkers as potential prognostic biomarkers. Therefore, the objective of this study was to compare the biomarkers of oxidative stress from gestations with and without complications, and also evaluate the delta of variation in these markers from the first gestational trimester. MATERIAL AND METHODS: A total of 45 pregnant women were evaluated during the three gestational trimesters, of whom 15 developed gestational complications by the end of gestation. The evaluated oxidative damage markers were thiobarbituric acid reactive substances and nitric oxide dosage. Evaluation of the antioxidant system was performed by the quantification of vitamin C, sulfhydryl groups, total antioxidant capacity, plasmatic iron reduction ability, the evaluation of catalase and delta-aminolevulinate dehydratase enzymatic activity. RESULTS: According to the results, the markers of oxidative damage are increased, and the antioxidant profile decreased, in the third trimester of complicated pregnancies as compared to uncomplicated pregnancies. Moreover, the delta of variation in both oxidative damage markers and antioxidants was higher in complicated gestations as compared to uncomplicated gestations, thus suggesting a higher oxidative stress in pregnancies with complications. CONCLUSIONS: Oxidative stress parameters appear altered in pregnant women with gestational complications. The markers to oxidative stress can be possible biomarkers, helping in understanding mechanisms underlying the associations between complications during pregnancy and various health outcomes.

Delta-aminolevulinate dehydratase enzyme activity and the oxidative profile of pregnant women being treated for acute toxoplasmosis.

The aim of this study was to investigate the clinical and oxidative profile, including the activity of the enzyme delta-aminolevulinate dehydratase (δ-ALA-D), in women who acquired toxoplasmosis during pregnancy and used the triple regimen (sulfadiazine + pyrimethamine + folinic acid [SPFA]) as treatment. These parameters have not been evaluated in pregnant women with toxoplasmosis who used the triple regimen. A total of 53 pregnant women were recruited and divided into two groups: control (C; n = 27) and acute toxoplasmosis (AT; n = 26). Clinical data and blood samples were obtained from all patients. The clinical profile was analyzed by checking parameters such as body mass index, blood pressure, and complete blood count. Oxidative stress was evaluated by quantifying protein (P-SH) and non-protein (NP-SH) thiol groups, vitamin C, plasma iron reduction capacity (FRAP), δ-ALA-D enzyme activity, reactive substances to thiobarbituric acid (TBARS), and nitric oxide (NO). Changes in hematological parameters (increased red cell distribution width and decreased hemoglobin and mean corpuscular hemoglobin concentration), increased antioxidant system (P-SH, NP-SH, FRAP, δ-ALA-D enzyme activity), as well as damage markers (TBARS and NO), were significantly elevated in pregnant women with toxoplasmosis, compared to those in the control group. Pregnant women treated for this acute infection showed increased damage markers, as well as a significant increase in the antioxidant system, including the activity of the δ-ALA-D enzyme. Given this evidence, it is suggested that these changes occur as a form of compensation, with a possible contribution from drug therapy.

Photobiomodulation and Sida tuberculata combination declines the inflammation's markers in knee-induced osteoarthritis.

The aim of this study was to assess potential combination effects of photobiomodulation therapy (PBMT) with Sida tuberculata extracts on the oxidative stress and antioxidant activity, as well as on the inflammatory process. Rats with knee osteoarthritis (OA) were treated with S. tuberculata extracts and PBMT (904 nm, 18 J/cm2). The animals were evaluated for nociception and edema. The blood, knee lavage and structures, spinal cord, and brainstem were collected for biochemical analyses (lipid peroxidation, protein carbonyl content, superoxide dismutase activity, non-protein thiol levels, and measurement of nitrite/nitrate). The knee structures were also used to measure cytokine levels. PBMT lowered the damage due to oxidative stress in the knee and at distant sites from the lesion. PBMT also reduced the levels of nitric oxide and cytokines, which could explain the nociception reduction mechanism. Similarly, S. tuberculata decreased the damage by oxidative stress, levels of nitrite/nitrate, and cytokines. The therapy combination reduced levels of cytokines and nitrite/nitrate. PBMT and S. tuberculata extracts reduced the oxidative stress and inflammation. It is noteworthy that PBMT increased the antioxidant activity in the knee and at sites distant from the lesion, contributing to a more significant decrease in nociception. The combination of therapies did not present significant effects on the analyzed parameters. Therefore, it is suggested that PBM is sufficient to minimize the signs and symptoms of the knee OA in our rat model.

Oxidative damage, inflammation, genotoxic effect, and global DNA methylation caused by inhalation of formaldehyde and the purpose of melatonin.

Formaldehyde (FA) exposure has been proven to increase the risk of asthma and cancer. This study aimed to evaluate for 28 days the FA inhalation effects on oxidative stress, inflammation process, genotoxicity, and global DNA methylation in mice as well as to investigate the potential protective effects of melatonin. For that, analyses were performed on lung, liver and kidney tissues, blood, and bone marrow. Bronchoalveolar lavage was used to measure inflammatory parameters. Lipid peroxidation (TBARS), protein carbonyl (PCO), non-protein thiols (NPSH), catalase activity (CAT), comet assay, micronuclei (MN), and global methylation were determined. The exposure to 5-ppm FA resulted in oxidative damage to the lung, presenting a significant increase in TBARS and NO levels and a decrease in NPSH levels, besides an increase in inflammatory cells recruited for bronchoalveolar lavage. Likewise, in the liver tissue, the exposure to 5-ppm FA increased TBARS and PCO levels and decreased NPSH levels. In addition, FA significantly induced DNA damage, evidenced by the increase of % tail moment and MN frequency. The pretreatment of mice exposed to FA applying melatonin improved inflammatory and oxidative damage in lung and liver tissues and attenuated MN formation in bone marrow cells. The pulmonary histological study reinforced the results observed in biochemical parameters, demonstrating the potential beneficial role of melatonin. Therefore, our results demonstrated that FA exposure with repeated doses might induce oxidative damage, inflammatory, and genotoxic effects, and melatonin minimized the toxic effects caused by FA inhalation in mice.