Kynurenic acid (KYNA) and quinolinic acid (QUIN) are metabolites produced in the degradation of tryptophan and have important neurological activities. KYNA/QUIN ratio changes are known to be ...associated with central nervous system disorders, such Alzheimer, Parkinson, and Huntington diseases. In the present study, we investigate the ability of KYNA in prevent the first events preceding QUIN-induced neurodegeneration in striatal slices of rat. We evaluated the protective effect of KYNA on oxidative status (reactive oxygen species production, antioxidant enzymes activities, lipid peroxidation, nitrite levels, protein and DNA damage, and iNOS immunocontent), mitochondrial function (mitochondrial mass, membrane potential, and respiratory chain enzymes), and Na
+
,K
+
-ATPase in striatal slices of rats treated with QUIN. Since QUIN alters the levels of Nrf2, we evaluated the influence of KYNA protection on this parameter. Striatal slices from 30-day-old Wistar rats were preincubated with KYNA (100 μM) for 15 min, followed by incubation with 100-μM QUIN for 30 min. Results showed that KYNA prevented the increase of ROS production caused by QUIN and restored antioxidant enzyme activities and the protein and lipid damage, as well as the Nrf2 levels. KYNA also prevented the effects of QUIN on mitochondrial mass and mitochondrial membrane potential, as well as the decrease in the activities of complex II, SDH, and Na
+
,K
+
-ATPase. We suggest that KYNA prevents changes in Nrf2 levels, oxidative imbalance, and mitochondrial dysfunction caused by QUIN in striatal slices. This study elucidates some of the protective effects of KYNA against the damage caused by QUIN toxicity.
•Chronic variable stress impairs aversive memory in rats.•Chronic variable stress induces oxidative stress and descreases Na+,K+-ATPase activity in amygdala and hippocampus.•Previous physical ...exercise to the stressful situations improves aversive memory and oxidative status changes in amygdala and hippocampus, as well as Na+,K+-ATPase activity in hippocampus rats.
Since stressful situations are considered risk factors for the development of depression and there are few studies evaluating prevention therapies for this disease, in the present study we evaluated the effect of previous physical exercise in animals subjected to chronic variable stress (CVS), an animal model of depression, on behavior tasks. We also investigated some parameters of oxidative stress and Na+, K+-ATPase activity, immunocontent and gene expression of alpha subunits in amygdala and hippocampus of rats. Young male rats were randomized into four study groups (control, exercised, stressed, exercised+stressed). The animals were subjected to controlled exercise treadmill for 20min,three times a week, for two months prior to submission to the CVS (40days). Results show that CVS impaired performance in inhibitory avoidance at 24h and 7days after training session. CVS induced oxidative stress, increasing reactive species, lipoperoxidation and protein damage, and decreasing the activity of antioxidant enzymes. The activity of Na+, K+-ATPase was decreased, but the immunocontents and gene expression of catalytic subunits were not altered. The previous physical exercise was able to improve performance in inhibitory avoidance at 24h after training; additionally, exercise prevented oxidative damage, but was unable to reverse completely the changes observed on the enzymatic activities. Our findings suggest that physical exercise during the developmental period may protect against aversive memory impairment and brain oxidative damage caused by chronic stress exposure later in life.
•FA supplementation did not alter the pregnancy development or the maternal behavior in rats.•High FA dose caused memory deficits in the dams.•FA supplementation did not change the Na+ K+ ATPase ...activity in the dams.•FA and HI did not alter the somatic growth and the neonatal reflexes of the pups.•HI and high FA dose decreased the Na+,K+ - ATPase activity in the pups’ hippocampus.
Folic acid (FA) is a B-complex vitamin important to the development of the fetus, being supplemented during pregnancy. Our recent findings showed that gestation supplementation (normal and excess doses) prevented the cognitive deficits and BDNF imbalance in adult rats that were submitted to neonatal hypoxia-ischemia (HI). To better understand this protective effect, the present study aimed to evaluate whether FA supplementation could be related to (1) maternal behavior, memory and Na+, K+ - ATPase activity in the hippocampus of the dams; (2) on somatic growth, early neurobehavioral development and Na+, K+ - ATPase activity in the hippocampus of the offspring; and (3) the effects of this supplementation in pups submitted to neonatal HI. Pregnant Wistar rats were divided into three groups, according to the diet they received during gestation: standard diet (SD), supplemented with 2 mg/kg of FA (FA2 – normal dose) and supplemented with 20 mg/kg of FA (FA20 –excessive dose). At the 7th PND pups were submitted to the Levine-Vannucci model of HI. During weaning the maternal behavior, the somatic growth and the neurobehavior development of pups were assessed. After weaning, the memory of the dams (by the Ox-maze task) and the Na+, K+ - ATPase activity in the hippocampus of both dams and offspring were evaluated. Considering the dams (1), both doses of FA did not alter the maternal behavior or the Na+, K+ - ATPase activity in the hippocampus, but a memory deficit was observed in the high FA-supplemented mothers. Considering the offspring (2), both FA doses did not affect the somatic growth or the neurobehavior development, but the FA20 pups had a decreased Na+, K+ - ATPase activity in the hippocampus. The FA supplementation did not change the parameters evaluated in the HI rats (3) and did not prevent the decreased Na+, K+ - ATPase activity in the hippocampus of the HI pups. These results indicate that normal FA supplementation dose does not influence the maternal behavior and memory and does not impact on the offspring early development in rats. Further studies are needed to confirm the effects of the high FA supplementation dose in the dams’ memory and in the Na+, K+ - ATPase activity in the hippocampus of the offspring.
•Ovariectomy in adult Wistar rats causes changes related to inflammatory system in hippocampus.•Cholinergic changes associated with ovariectomy also were observed in hippocampus of adult Wistar ...rats.•Vitamin D partially improve the inflammatory changes observed in hippocampus of adult Wistar rats submitted to ovariectomy.
The aim of this study was to verify the effects of ovariectomy (OVX) and/or vitamin D supplementation (VIT D) on inflammatory and cholinergic parameters in hippocampus, as well as on serum estradiol and VIT D levels of rats. Ninety-day-old female Wistar rats were randomly divided into four groups: SHAM, OVX, VIT D or OVX + VIT D. Thirty days after OVX, VIT D (500 IU/kg/day) was supplemented by gavage, for 30 days. Approximately 12 h after the last VIT D administration, rats were euthanized and hippocampus and serum were obtained for further analyses. Results showed that OVX rats presented a decrease in estradiol levels when compared to control (SHAM). There was an increase in VIT D levels in the groups submitted to VIT D supplementation. OVX increased the immunocontent of nuclear p-NF-κB/p65, TNF-α and IL-6 levels. VIT D partially reversed the increase in p-NF-κB/p65 immunocontent and IL-6 levels. Regarding cholinergic system, OVX caused an increase in acetylcholinesterase activity without changing acetylcholinesterase and choline acetyltransferase immunocontents. VIT D did not reverse the increase in acetylcholinesterase activity caused by OVX. These results demonstrate that OVX alters inflammatory and cholinergic parameters and that VIT D supplementation, at the dose used, partially reversed the increase in immunocontent of p-NF-Kb/p65 and IL-6 levels, but it was not able to reverse other parameters studied. Our findings may help in the understanding of the brain changes that occurs in post menopause period and open perspectives for futures research involving VIT D therapies.
The aim of this study was to investigate the effect of ovariectomy (OVX), a surgical model of menopause, and/or vitamin D (VIT D) supplementation on oxidative status, DNA damage, and telomere length ...in hippocampus of rats at two ages. Ninety-day-old (adult) or 180-day-old (older) female Wistar rats were divided into four groups: SHAM, OVX, VIT D, and OVX + VIT D. Thirty days after OVX, rats were supplemented with VIT D (500 IU/kg) by gavage, for a period of 30 days. Results showed that OVX altered antioxidant enzymes, increasing the activities of catalase in adult rats and superoxide dismutase in older rats. VIT D
per se
increased the activities of catalase and superoxide dismutase in older rats, but not in adult rats. VIT D supplementation to OVX (OVX + VIT D) rats did not reverse the effect of OVX on catalase in adult rats, but it partially reversed the increase in superoxide dismutase activity in older rats. OVX increased DNA damage in hippocampus of adult and older rats. VIT D
per se
reduced DNA damage, and when associated to OVX, it partially reversed this alteration. Additionally, OVX caused a telomere shortening in older rats, and VIT D was able to reverse such effect. Taken together, these results demonstrate that surgical menopause in rats causes hippocampal biochemical changes and VIT D appears, at least in part, to act in a beneficial way.
Folic acid (FA) is a B-complex vitamin important to the development of the fetus, being supplemented during pregnancy. Our recent findings showed that gestation supplementation (normal and excess ...doses) prevented the cognitive deficits and BDNF imbalance in adult rats that were submitted to neonatal hypoxia-ischemia (HI). To better understand this protective effect, the present study aimed to evaluate whether FA supplementation could be related to (1) maternal behavior, memory and Na+, K+ - ATPase activity in the hippocampus of the dams; (2) on somatic growth, early neurobehavioral development and Na+, K+ - ATPase activity in the hippocampus of the offspring; and (3) the effects of this supplementation in pups submitted to neonatal HI. Pregnant Wistar rats were divided into three groups, according to the diet they received during gestation: standard diet (SD), supplemented with 2 mg/kg of FA (FA2 – normal dose) and supplemented with 20 mg/kg of FA (FA20 –excessive dose). At the 7th PND pups were submitted to the Levine-Vannucci model of HI. During weaning the maternal behavior, the somatic growth and the neurobehavior development of pups were assessed. After weaning, the memory of the dams (by the Ox-maze task) and the Na+, K+ - ATPase activity in the hippocampus of both dams and offspring were evaluated. Considering the dams (1), both doses of FA did not alter the maternal behavior or the Na+, K+ - ATPase activity in the hippocampus, but a memory deficit was observed in the high FA-supplemented mothers. Considering the offspring (2), both FA doses did not affect the somatic growth or the neurobehavior development, but the FA20 pups had a decreased Na+, K+ - ATPase activity in the hippocampus. The FA supplementation did not change the parameters evaluated in the HI rats (3) and did not prevent the decreased Na+, K+ - ATPase activity in the hippocampus of the HI pups. These results indicate that normal FA supplementation dose does not influence the maternal behavior and memory and does not impact on the offspring early development in rats. Further studies are needed to confirm the effects of the high FA supplementation dose in the dams’ memory and in the Na+, K+ - ATPase activity in the hippocampus of the offspring.
Objetivo: Identificar os serviços farmacêuticos realizados na Atenção Primária à Saúde (APS) em uma cidade do Sul do Brasil e entender quais as potencialidades e as fragilidades para a sua ...realização, segundo a percepção dos farmacêuticos. Método: Trata-se de um estudo qualitativo com farmacêuticos e residentes que atuam em Farmácias de Referência Distritais. Os farmacêuticos responderam um questionário para auxiliar na identificação dos serviços farmacêuticos realizados na APS. Considerou-se serviço farmacêutico realizado quando o nível de concordância foi maior ou igual a 70% (técnica Delphi). Os serviços que não obtiveram concordancia foram selecionados e discutidos em uma oficina presencial, utilizando uma técnica de consenso (comitê tradicional). Após a oficina, realizou-se um grupo focal para compreender as potencialidades e dificuldades de execução dos serviços identificados. Resultados: Foram identificados 8 serviços farmacêuticos técnicos gerenciais e 26 serviços farmacêuticos técnicos assistenciais executados ou com potencial de execução em serviços da APS na cidade estudada. Entre as potencialidades, destacam-se o reconhecimento dos serviços farmacêuticos pelas equipes de saúde e o apoio da gestão local. Os farmacêuticos apontaram a sobrecarga de trabalho causada pela grande demanda de atividades e pela ausência de equipes de farmácia e a falta de formação clínica dos profissionais para a atuação na APS como um dificultador, em especial para a realização de serviços farmacêuticos técnicos assistenciais. Conclusão: Os achados da pesquisa reforçam a necessidade de ampliação das Farmácias de Referência, assim como de farmacêuticos capacitados para atuação na APS.
Objective: To identify the pharmaceutical services provided in Primary Health Care (PHC) in a city in southern Brazil and understand the potential and weaknesses in carrying them out, according to ...the perception of pharmacists. Methods: This is a qualitative study with pharmacists and residents who work in District Reference Pharmacies. Pharmacists completed a questionnaire to help identify pharmaceutical services provided in PHC. A pharmaceutical service was considered performed when the level of agreement was greater than or equal to 70% (Delphi technique). The services that did not reach agreement were selected and discussed in a face-to-face workshop, using a consensus technique (traditional committee). After the workshop, a focus group was held to understand the potential and difficulties in implementing the identified services. Results: Eight managerial technical pharmaceutical services and 26 technical assistance pharmaceutical services were identified, carried out or with the potential to be carried out in PHC services in the city studied. Among the potentialities, the recognition of pharmaceutical services by health teams and the support of local management stand out. Pharmacists pointed out the work overload caused by the great demand for activities and the absence of pharmacy teams and the lack of clinical training of professionals to work in PHC as a complicating factor, especially when carrying out technical pharmaceutical assistance services. Conclusion: The research findings reinforce the need to expand Reference Pharmacies, as well as pharmacists trained to work in PHC.
