Melatonin effects on oxidative stress and on TLR4/NF-kß inflammatory pathway in the right ventricle of rats with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterised by an increase in mean pulmonary arterial pressure and a compromised the right ventricle (RV), together with progression to heart failure and premature death. Studies have evaluated the role of melatonin as a promising therapeutic strategy for PAH. The objective of this study was to evaluate melatonin's effects on oxidative stress and on the TLR4/NF-kß inflammatory pathway in the RV of rats with PAH. Male Wistar rats were divided into the following groups: control, monocrotaline (MCT), and monocrotaline plus melatonin groups. These two last groups received one intraperitoneal injection of MCT (60 mg/kg) on the first day of experimental protocol. The monocrotaline plus melatonin group received 10 mg/kg/day of melatonin by gavage for 21 days. Echocardiographic analysis was performed, and the RV was collected for morphometric analysis oxidative stress and molecular evaluations. The main findings of the present study were that melatonin administration attenuated the reduction in RV function that was induced by monocrotaline, as assessed by TAPSE. In addition, melatonin prevented RV diastolic area reduction caused by PAH. Furthermore, animals treated with melatonin did not show an increase in ROS levels or in NF-kß expression. In addition, the monocrotaline plus melatonin group showed a reduction in TLR4 expression when compared with control and monocrotaline groups. To our knowledge, this is the first study demonstrating a positive effect of melatonin on the TLR4/NF-kß pathway in the RV of rats with PAH. In this sense, this study makes it possible to think of melatonin as a possible ally in mitigating RV alterations caused by PAH.

Melatonin improves nitric oxide bioavailability in isoproterenol induced myocardial injury.

Isoproterenol administration is associated with cardiac inflammation and decreased NO availability. Melatonin has been reported to have cardioprotective effect. The aim of this study was to investigate the effect of melatonin on NO bioavailability and inflammation in myocardial injury induced by isoproterenol. Isoproterenol was administrated in male Wistar rats for 7 days to induce cardiac injury. The animals were divided into 3 groups: Control, Isoproterenol, Isoproterenol + Melatonin. Animals received melatonin for 7 days. Echocardiographic analysis was performed and the hearts were collected for molecular analysis. Animals that received isoproterenol demonstrated a reduction in left ventricle systolic and diastolic diameter, indicating the presence of concentric hypertrophy. Melatonin was able to attenuate this alteration. Melatonin also improved NO bioavailability and decreased NF-κß, TNFα and IL-1ß expression. In conclusion, melatonin exhibited a cardioprotective effect which was associated with improving NO bioavailability and decreasing the pro-inflammatory proteins.

Evaluation of the immediate effects of a single transcranial direct current stimulation session on astrocyte activation, inflammatory response, and pain threshold in naïve rats.

Transcranial direct current stimulation (tDCS) has demonstrated clinical benefits such as analgesia, anti-inflammatory, and neuroprotective effects. However, the mechanisms of action of a single tDCS session are poorly characterized. The present study aimed to evaluate the effects of a single tDCS session on pain sensitivity, inflammatory parameters, and astrocyte activity in naive rats. In the first experiment, sixty-day-old male Wistar rats (n = 95) were tested for mechanical pain threshold (von Frey test). Afterward, animals were submitted to a single bimodal tDCS (0.5 mA, 20 min) or sham-tDCS session. According to the group, animals were re-tested at different time intervals (30, 60, 120 min, or 24 h) after the intervention, euthanized, and the cerebral cortex collected for biochemical analysis. A second experiment (n = 16) was performed using a similar protocol to test the hypotheses that S100B levels in the cerebrospinal fluid (CSF) are altered by tDCS. Elisa assay quantified the levels of tumor necrosis factor-alfa (TNF-α), interleukin-10 (IL10), S100 calcium-binding protein B (S100B), and Glial fibrillary acidic protein (GFAP). Data were analyzed using ANOVA and independent t-test (P < 0.05). Results showed that tDCS decreased pain sensitivity (30 and 60 min), cerebral TNF-α and S100B levels (30 min). CSF S100B levels increased 30 min after intervention. There were no differences in IL10 and GFAP levels. TCDS showed analgesic, anti-inflammatory, and neuroprotective effects in naive animals. Therefore, this non-invasive and inexpensive therapy may potentially be a preemptive alternative to reduce pain, inflammation, and neurodegeneration in situations where patients will undergo medical procedures (e.g., surgery).

Ibuprofen during gestation prevents some changes in physical and reflex development in offspring in a model of hyperleucinemia and maternal inflammation.

Maple Syrup Urine Disease (MSUD) is caused by a severe deficiency in the branched-chain ketoacid dehydrogenase complex activity. Patients MSUD accumulate the branched-chain amino acids leucine (Leu), isoleucine, valine in blood, and other tissues. Leu and/or their branched-chain α-keto acids are linked to neurological damage in MSUD. When immediately diagnosed and treated, patients develop normally. Inflammation in MSUD can elicit a metabolic decompensation crisis. There are few cases of pregnancy in MSUD women, and little is known about the effect of maternal hyperleucinemia on the neurodevelopment of their babies. During pregnancy, some intercurrences like maternal infection or inflammation may affect fetal development and are linked to neurologic diseases. Lipopolysaccharide is widely accepted as a model of maternal inflammation. We analyzed the effects of maternal hyperleucinemia and inflammation and the possible positive impact the use of ibuprofen in Wistar rats on a battery of physics (ear unfolding, hair growing, incisors eruption, eye-opening, and auditive channel opening) and neurological reflexes (palmar grasp, surface righting, negative geotaxis, air-righting, and auditory-startle response) maturation parameters in the offspring. Maternal hyperleucinemia and inflammation delayed some physical parameters and neurological reflexes, indicating that both situations may be harmful to fetuses, and ibuprofen reversed some settings.

Melanin: Quantification and protection against oxidative stress in chromoblastomycosis agents.

Chromoblastomycosis (CBM) is a chronic cutaneous and subcutaneous infection caused by melanized fungal species. We quantified the extractable melanin of 77 strains of CBM agents distributed within five genera. Moreover, resistance to oxidative stress was evaluated in strains exposed or not to the melanin inhibitor tricyclazole. The median percentage of melanin mass extracted from dry fungal mass varied from 0.69 (Rhinocladiella similis) to 3.81 (Phialophora americana). Inhibition of melanin synthesis decreased survival rates to hydrogen peroxide. Together, these data highlight the importance of melanin in CBM agents.

Evaluation of hematological, biochemical parameters and thiol enzyme activity in chrome plating workers.

The most commonly used solution in chrome plating bath is chromic acid (hexavalent Cr), and a considerable amount of mists is released into the air and consequently produce hazards to workers. Thus, the aim of this study was to evaluate whether the biomarker of exposure to metals, specially Cr levels, presents associations with hematological and biochemical parameters and if they can alter the activity of enzymes that contain thiol groups such as pyruvate kinase, creatine kinase, adenylate kinase, and δ-aminolevulinate dehydratase. Fifty male chrome plating workers were used for exposed group and 50 male non-exposed workers for control group. For that, biological monitoring was performed through quantification of metals on total blood and urine by inductively coupled plasma mass spectrometry (ICP-MS) and enzyme activity was performed by spectrometry in erythrocytes. In addition, chromium levels in water was quantified and ecotoxicology assay was performed with Allium cepa test. The results demonstrated that blood and urinary chromium levels in exposed group were higher than the control group (p < 0.0001). Furthermore, decreased activity of enzymes was found in those that contain thiol groups from exposed group when compared with the control group (p < 0.001). The water analysis did not present a statistical difference between control and exposed groups (p > 0.05), demonstrating that water did not seem to be the source of contamination. In summary, our findings indicated some toxicology effects observed in the exposed group, such as thiol enzyme inhibition, mainly associated with occupational exposure in chrome plating and besides the presence of other metals, and Cr demonstrated to influence the activity of the enzymes analyzed in this research.

Phenylalanine induces oxidative stress and decreases the viability of rat astrocytes: possible relevance for the pathophysiology of neurodegeneration in phenylketonuria.

The aim of this study was to investigate the effects of phenylalanine on oxidative stress and some metabolic parameters in astrocyte cultures from newborn Wistar rats. Astrocytes were cultured under four conditions: control (0.4 mM phenylalanine concentration in the Dulbecco's Modified Eagle Medium (DMEM) solution), Phe addition to achieve 0.5, 1.0 or 1.5 mM final phenylalanine concentrations. After 72 h the astrocytes were separated for the biochemical measurements. Overall measure of mitochondrial function by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell viability measured by lactate dehydrogenase (LDH) assays indicated that phenylalanine induced cell damage at the three concentrations tested. The alteration on the various parameters of oxidative stress indicated that phenylalanine was able to induce free radicals production. Therefore, our results strongly suggest that Phe at concentrations usually found in PKU induces oxidative stress and consequently cell death in astrocytes cultures. Considering the importance of the astrocytes for brain function, it is possible that these astrocytes alterations may contribute to the brain damage found in PKU patients.