Kinin B1 receptor deficiency protects mice fed by cafeteria diet from abnormal glucose homeostasis.

The kallikrein-kinin system has been implicated in body weight and glucose homeostasis. Their major effectors act by binding to the kinin B2 and B1 receptors. It was assessed the role of the kinin B1 receptor in weight and glucose homeostasis in B1 receptor knockout mice (B1RKO) subjected to a cafeteria diet (CAF). Wild-type (WT) and B1RKO male mice (C57BL/6 background; 8 weeks old) were fed a standard diet (SD) or CAF for 14 weeks, ad libitum, and four groups were formed: WT-SD; B1RKO-SD; WT-CAF; B1RKO-CAF. Body weight and food intake were assessed weekly. It was performed glucose tolerance (GTT) and insulin tolerance tests (ITT), and HOMA-IR, HOMA-ß and HOMA-ß* 1/HOMA-IR were calculated. Islets from WT and B1RKO were isolated in order to measure the insulin secretion. Western blot was used to assess the hepatic AKT phosphorylation and qPCR to assess gene expression. CAF induced a higher body mass gain in B1RKO compared to WT mice. CAF diet increased epididymal fat depot mass, hepatic fat infiltration and hepatic AKT phosphorylation in both genotypes. However, B1RKO mice presented lower glycemic response during GTT when fed with CAF, and a lower glucose decrease in the ITT. This higher resistance was overcomed with higher insulin secretion when stimulated by high glucose, resulting in higher glucose uptake in the GTT when submitted to CAF, despite lower insulin sensitivity. Islets from B1RKO delivered 4 times more insulin in 3-month-old mice than islets from WT. The higher insulin disposition index and high insulin delivery of B1RKO can explain the decreased glucose excursion during GTT. In conclusion, CAF increased the ß-cell function in B1RKO mice, compensated by the diet-induced insulin resistance and resulting in a healthier glycemic response despite the higher weight gain.

Behind teaching-learning strategies in physiology: perceptions of students and teachers of Brazilian medical courses.

The teaching-learning process must constantly overcome the barriers imposed by rapid scientific and technological advances, as well as changes in the profiles of students and access to information. This study intended to analyze the perceptions of students and professors of medical courses of the teaching-learning strategies used in physiology at different Brazilian universities as well as the factors that influence or hinder the learning of this discipline. Questionnaires were analyzed from 174 students and 16 professors of physiology from medical courses of 20 higher education institutions (public and private) in a southern Brazilian state. The teaching strategies most used by physiology teachers coincided with the classroom activities that students consider to have the greatest contribution to their learning (expository classes/lectures, tests and questionnaires, problem-based learning/clinical case studies, and demonstrative/practical classes). It was also evidenced that teachers' didactic is considered as a very influencing factor for the students during their learning process, whereas the teachers pointed out daily pedagogical practice as the most relevant factor in the development of their skills within the classroom. In addition, some factors hindering the teaching-learning process of physiology were identified by the respondents, such as large amounts of information, little time for study outside the classroom, previous knowledge, and intrinsic difficulty of the discipline. Finally, students tended to study alone and generally used teachers' slides and their own notes as study materials. The continuous assessment of the perceptions, needs, and difficulties of students and teachers plays an essential role in improving the teaching-learning process.

Long-Lasting Actions of Progesterone Protect the Neonatal Brain Following Hypoxia-Ischemia.

Neonatal hypoxia-ischemia (HI) is the leading cause of mortality and morbidity in newborns, occurring in approximately 2% of live births. Neuroprotective actions of progesterone (PROG) have already been described in animal models of brain lesions. However, PROG actions on neonates are still controversial. Here, we treated male Wistar rats exposed to HI with PROG. Five experimental groups were defined (n = 6/group) according to the scheme of PROG administration (10 mg/kg): SHAM (animals submitted to a fictitious surgery, without ischemia induction, and maintained under normoxia), HI (animals undergoing HI), BEFORE (animals undergoing HI and receiving PROG immediately before HI), AFTER (animals undergoing HI and receiving PROG at 6 and 24 h after HI) and BEFORE/AFTER (animals undergoing HI and receiving PROG immediately before and 6 and 24 h after HI). At P14 (7 days following HI), the volumes of lesion of the cerebral hemisphere and the hippocampus ipsilateral to the cerebral ischemia were evaluated, along with p-Akt, cleaved caspase-3 and GFAP expression in the hippocampus. PROG reduces the loss of brain tissue caused by HI. Moreover, when administered after HI, PROG was able to increase p-Akt expression and reduce both cleaved caspase-3 and GFAP expression in the hippocampus. In summary, it was possible to observe a neuroprotective action of PROG on the brain of neonatal animals exposed to experimental HI. This is the first study suggesting PROG-dependent Akt activation is able to regulate negatively cleaved caspase-3 and GFAP expression protecting neonatal hypoxic-ischemic brain tissue from apoptosis and reactive gliosis.

Análise bioquímica da saliva de pacientes com deficiência cognitiva e física como estratégia de aula prática de Bioquímica no curso de Odontologia / Biochemical analysis of the saliva of patients with cognitive and physical disabilities as a practical Biochemistry class strategy in the Dentistry course

Diante da importância do ensino de Bioquímica na formação do futuro cirurgião-dentista, o objetivo é apresentar uma estratégia pedagógica que possibilita a articulação dos conceitos moleculares básicos da disciplina no entendimento da complexidade das doenças bucais e sistêmicas, por meio da análise bioquímica da saliva de pacientes com deficiência cognitiva e física do Centro de Assistência Odontológica à Pessoa com Deficiência (CAOE) da Faculdade de Odontologia de Araçatuba-Universidade Estadual Paulista(UNESP).Para tanto, grupos de cinco estudantesrealizaram as análises na saliva, coletada por um cirurgião-dentista doCAOE. Imediatamente após a coleta, foi determinado o fluxo salivar, pH e a capacidade tamponante. Na sequência, a saliva foi centrifugada, fracionada e armazenada a -20 °C até o momento das análises bioquímicas. Durante as aulas práticas, realizaram-se os seguintes ensaios, utilizando kitscomerciais: proteína total, α-amilase, fosfatase alcalina, ácido úrico, glicose, aspartato aminotransferase, cálcio e fósforo. Ao final do ano letivo, os estudantes apresentaram relatório contextualizando os resultados com a saúde bucal e sistêmica do paciente. Plantões de dúvidas com monitores e professores auxiliaram na interpretação da ficha de anamnese e nas correlações dos parâmetros clínicosbucais e sistêmicos. Para os estudantes ingressantes, foi a primeira oportunidade de integrar o conhecimento teórico às condições clínicas de um paciente. Conclui-se que a estratégia adotada é viável e pode beneficiar educadores que buscam alternativas que permitam a integração das ciências básicas e clínicas ao ensino de Bioquímica para a Odontologia (AU).

Given the importance of teaching biochemistry in dental surgeon trainingcourses, the objective was to present a pedagogical strategy that enables the articulation of basic molecular concepts within the subject, allowing a betterunderstanding of the complexity of oral and systemic diseases, through the biochemical analysis of saliva from patients with cognitive and physical disabilities at the Dental Assistance Center for Disabled Persons (CAOE)of the School of Dentistry, Araçatuba -São Paulo State University (UNESP).For this purpose, groups of five students analyzedthesaliva collected by a dentalsurgeon from CAOE. Immediately after collection, salivary flow, pH, and buffering capacity were determined. Subsequently, the saliva was centrifuged, fractionated, and stored at -20°C until the time of biochemical analysis. During the practical classes, using commercial kits, the samples were tested for: total protein, α-amylase, alkaline phosphatase, uric acid, glucose, aspartate aminotransferase, calcium, and phosphorus. At the end of the school year, students presented a report contextualizing the results with the patient's oral and systemic health. Tutoring sessions with monitors and teachers helped in the interpretation of the anamnesis form and the correlations of oral and systemic clinical parameters. For incoming students, this was the first opportunity to integrate theoretical knowledge with clinical perspectives.It is concluded that the adopted strategy is viable and can benefit educators who seek alternatives that allow the integration of basic and clinical sciences forteaching Biochemistry in Dentistry (AU).

Pedagogical training profile of basic health sciences faculty in biomedical and related fields at Brazilian public and private higher education institutions.

Historically, Brazilian higher education teachers' pedagogical training has not been a concern. Even today, a graduate degree is the main requirement to be a faculty member. However, a set of competencies is necessary to teach: pedagogical competency, political competency, and knowledge of specific content. Most graduate training covers only knowledge of specific content. Therefore, this work aimed to outline the profile of basic health sciences faculty members teaching in biomedical and related fields regarding their undergraduate and graduate training, as well as the initial and continued pedagogical training in Brazilian public and private higher education institutions (HEIs). An electronic questionnaire was sent to these professionals, and a total of 763 responses were analyzed (66.4% from public and 33.6% from private HEIs). Compared with private HEI faculty, faculty from public HEIs were more experienced in teaching, and more time had passed since they finished their graduate training. On the other hand, faculty from private HEIs had a more intense undergraduate teaching workload than faculty from public HEIs. Additionally, faculty from private HEIs attended more extensive and more frequent pedagogical training activities (PTAs). Both groups expressed that activities closely related to their classroom practice and recognition for good pedagogical performance were incentives for their participation in PTAs. In conclusion, differences between the faculty from public and private HEIs may be due to the characteristics of HEIs themselves. Hypothetically, private HEIs focus on teaching, which may explain why faculty from these institutions seek improvement in this area, whereas public HEIs focus on research.

The metabolic and neuroinflammatory changes induced by consuming a cafeteria diet are age-dependent.

OBJECTIVES: To compare the effects of a palatable cafeteria diet on serum parameters and neuroinflammatory markers of young and aged female Wistar rats. METHODS: Three-month-old (young) and 18-month-old (aged) female Wistar rats had access to a cafeteria diet (Caf-Young, Caf-Aged) or a standard chow diet (Std-Young, Std-Aged). RESULTS: The Caf-Young group showed a higher food consumption, weight gain, visceral fat depot, serum insulin and leptin levels, and the insulin resistance index (HOMA-IR) than the Std-Young group. The Caf-Aged group exhibited an increase in interleukin-1 levels in the cerebral cortex and hippocampus. The number of GFAP-positive cells did not differ between the groups, but there was a diet effect in the cerebral cortex and an age effect in the hippocampus. Phospho-tau expression did not differ between the groups. DISCUSSION: The 3- and 18-month-old rats responded differently to a cafeteria diet. Insulin and leptin levels are elevated in young animals fed a cafeteria diet, whereas aged animals are prone to neuroinflammation (indicated by an increase in interleukin-1ß levels). A combination of hypercaloric diet and senescence have detrimental effects on the inflammatory response in the brain, which may predispose to neurological diseases.

Female rats are more susceptible to metabolic effects of dehydroepiandrosterone treatment.

Dehydroepiandrosterone (DHEA) is a steroid hormone that presents several effects on metabolism; however, most of the studies have been performed on male animals, while few authors have investigated possible sex differences regarding the metabolic effects of DHEA. Therefore, the aim of this study was to evaluate the effect of different doses of DHEA on metabolic parameters of male and ovariectomized female Wistar rats. Sex differences were found in the metabolism of distinct substrates and in relation to the effect of DHEA. In respect to the glucose metabolism in the liver, the conversion of glucose to CO2 and the synthesis of lipids from glucose were 53% and 33% higher, respectively, in males. Also, DHEA decreased hepatic lipogenesis only in females. Regarding the hepatic glycogen synthesis pathway, females presented 73% higher synthesis than males, and the effect of DHEA was observed only in females, where it decreased this parameter. In the adipose tissue, glucose uptake was 208% higher in females and DHEA decreased this parameter. In the muscle, glucose uptake was 168% higher in females and no DHEA effect was observed. In summary, males and females present a different metabolic profile, with females being more susceptible to the metabolic effects of DHEA.

Effects of progesterone on the neonatal brain following hypoxia-ischemia.

Progesterone displays a strong potential for the treatment of neonatal hypoxic-ischemic encephalopathy since it has been shown to be beneficial in the treatment of the central nervous system injuries in adult animals. Here, we evaluated the effects of the administration of progesterone (10 mg/kg) in seven-days-old male Wistar rats submitted to neonatal hypoxia-ischemia (HI). Progesterone was administered immediately before ischemia and/or 6 and 24 h after the onset of hypoxia. The body weight of the animals, the volume of brain lesion and the expression of p-Akt and procaspase-3 in the hippocampus were evaluated. All animals submitted to HI showed a reduction in the body weight. However, this reduction was more remarkable in those animals which received progesterone before surgery. Administration of progesterone was unable to reduce the volume of brain damage caused by HI. Moreover, no significant differences were observed in the expression of p-Akt and procaspase-3 in animals submitted to HI and treated with either progesterone or vehicle. In summary, progesterone did not show a neuroprotective effect on the volume of brain lesion in neonatal rats submitted to hypoxia-ischemia. Furthermore, progesterone was unable to modulate p-Akt and procaspase-3 signaling pathways, which may explain the absence of neuroprotection. On the other hand, it seems that administration of progesterone before ischemia exerts some systemic effect, leading to a remarkable reduction in the body weight.

Aversive and non-aversive memory impairment in the mucopolysaccharidosis II mouse model.

Hunter syndrome (MPS II, OMIM 309900) is a lysosomal storage disorder due to deficient iduronate sulphatase activity. Patients present multiple cognitive alterations, and the aim of this work was to verify if MPS II mice also present some progressive cognitive alterations. For that, MPS II mice from 2 to 6 months of age were submitted to repeated open field and inhibitory avoidance tests to evaluate memory parameters. MPS II mice presented impaired memory at 6 months evaluated by open field test. They also performed poorly in the inhibitory avoidance test from 4 months. We conclude that MPS II mice develop cognitive alterations as the disease progresses. These tests can be used in the future to study the efficacy of therapeutic approaches in the central nervous system.

Effects of isolated vitamin B6 supplementation on oxidative stress and heart function parameters in experimental hyperhomocysteinemia

Introduction: The purpose of this study was to investigate the effects of isolated vitamin B6 (VB6 ) supplementation on experimental hyperhomocysteinemia (Hhe) induced by homocysteine thiolactone (HcyT). Methods: Fifteen male Wistar rats were divided into three groups according to their treatment. Animals received water and food ad libitum and an intragastric probe was used to administer water for 60 days (groups: CB6, HcyT, and HB6 ). On the 30th day of treatment, two groups were supplemented with VB6 in the drinking water (groups: CB6 and HB6 ). After 60 days of treatment, homocysteine (Hcy), cysteine, and hydrogen peroxide concentration, nuclear factor (erythroid-derived 2)-like 2 (NRF2) and glutathione S-transferase (GST) immunocontent, and superoxide dismutase (SOD), catalase (CAT), and GST activities were measured. Results: The HcyT group showed an increase in Hcy concentration (62%) in relation to the CB6 group. Additionally, GST immunocontent was enhanced (51%) in the HB6 group compared to the HcyT group. Also, SOD activity was lower (17%) in the HB6 group compared to the CB6 group, and CAT activity was higher in the HcyT group (53%) compared to the CB6 group. Ejection fraction (EF) was improved in the HB6 group compared to the HcyT group. E/A ratio was enhanced in the HB6 group compared to the CB6 group. Correlations were found between CAT activity with myocardial performance index (MPI) (r = 0.71; P = 0.06) and E/A ratio (r = 0.6; P = 0.01), and between EF and GST activity (r = 0.62; P = 0.02). Conclusions: These findings indicate that isolated VB6 supplementation may lead to the reduction of Hcy concentration and promotes additional benefits to oxidative stress and heart function parameters (AU)

Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats.

In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats.

Asymmetric effects of low doses of progesterone on GABA(A) receptor α4 subunit protein expression in the olfactory bulb of female rats.

The aim of this study was to evaluate the effect of progesterone on the protein expression of α4 subunit of GABA(A) receptor, serotonin transporter (SERT), Akt, Erk, and caspase-3 in the olfactory bulb (OB) of female rats exposed to the forced swimming test (FST). Female rats were injected daily with progesterone (0.4 mg/kg body mass) or vehicle during 2 complete oestrous cycles and exposed to the FST, and the protein expression of GABA(A) receptor α4 subunit, SERT, Akt, Erk, and caspase-3 in the OB were evaluated. Progesterone increased the expression of the α4 subunit in the right OB and decreased its expression in the left OB, although it did not change the expression of other proteins. In summary, our findings indicate that progesterone has an asymmetric modulatory effect on the expression of GABA(A) receptor α4 subunit in the OB. This effect could be related to the antidepressant-like effect of progesterone in female rats.

Satisfação, Percepção de Aprendizagem e Desempenho em Vídeo aula e Aula Expositiva / Satisfaction, Perceived Learning and Performance in Video Lesson andLecture

Educadores têm se perguntado sobre estratégias adequadas para interagir com uma geração de alunos que tem acesso a modernos meios de comunicação liderados pela Internet. Este estudo comparou dois grupos de alunos de graduação,um exposto a uma aula expositiva (AE, n=81) e o outro a uma vídeo-aula (VA, n=60), avaliando o desempenho (DES) em pré e pós-testes, satisfação(SAT) e percepção de aprendizagem (PA). Foram analisadas correlações entre SAT e PA e entre ambase o DES. Houve melhora de DES (teste de Wilcoxon)de ambos os grupos, sem diferença entre eles (testede Mann-Whitney); os alunos ficaram satisfeitos e expressaram boa percepção de aprendizagem(teste de Qui-Quadrado); houve correlação entre SAT e PA, e as correlações entre SAT e DES e entre PA e DES foram significativas, porém baixas (teste de correlação de Spearman). Conclui-se que VAe AE são adequadas e promovem aprendizado dos alunos que se sentiram satisfeitos e com a percepção de que aprenderam o conteúdo. Sugere seque as metodologias possam ser utilizadas pelo professor de forma complementar, ressaltando a importância da construção de diálogos que sintonizem metodologias clássicas de ensino, como a aula expositiva, com novas tecnologias, como a vídeo-aula, que possam ser utilizadas com fins educacionais.

Educators have been wondering about the mostappropriate strategies to interact with a generationof students who has access to modern means ofcommunication, led by the Internet. This studycompared two groups of undergraduate students,one exposed to a lecture (L, n=81) and the otherto a video lesson (VL, n=60) through performanceevaluation (PER) in pre- and post-tests, satisfaction(SAT) and perceived learning (PL). The correlationsbetween SAT and PL and between both and PER wereanalyzed. The data showed an improvement of PER(Wilcoxon test) in both groups, without differencebetween them (Mann-Whitney test); both groups ofstudents were satisfied and perceived good sense oflearning (Chi-Square test); there was a correlationbetween SAT and PL and the correlation between SATand DES and between DES and PA were significant,but low (Spearman test). In conclusion, L and VL areappropriate and promote learning and the studentsfelt satisfied and with the perception that theylearned the content of the subject. It is suggestedthat both methodologies can be used by the teacheras a reinforcement and in a complementary manner,emphasizing the importance of constructing dialogicbridges able to match classical teaching methodssuch as lecturing with new technologies, as the videolesson, that can be used for educational purposes.

Satisfação, Percepção de Aprendizagem e Desempenho em Vídeo aula e Aula Expositiva / Satisfaction, Perceived Learning and Performance in Video Lesson andLecture

Educadores têm se perguntado sobre estratégias adequadas para interagir com uma geração de alunos que tem acesso a modernos meios de comunicação liderados pela Internet. Este estudo comparou dois grupos de alunos de graduação,um exposto a uma aula expositiva (AE, n=81) e o outro a uma vídeo-aula (VA, n=60), avaliando o desempenho (DES) em pré e pós-testes, satisfação(SAT) e percepção de aprendizagem (PA). Foram analisadas correlações entre SAT e PA e entre ambase o DES. Houve melhora de DES (teste de Wilcoxon)de ambos os grupos, sem diferença entre eles (testede Mann-Whitney); os alunos ficaram satisfeitos e expressaram boa percepção de aprendizagem(teste de Qui-Quadrado); houve correlação entre SAT e PA, e as correlações entre SAT e DES e entre PA e DES foram significativas, porém baixas (teste de correlação de Spearman). Conclui-se que VAe AE são adequadas e promovem aprendizado dos alunos que se sentiram satisfeitos e com a percepção de que aprenderam o conteúdo. Sugere seque as metodologias possam ser utilizadas pelo professor de forma complementar, ressaltando a importância da construção de diálogos que sintonizem metodologias clássicas de ensino, como a aula expositiva, com novas tecnologias, como a vídeo-aula, que possam ser utilizadas com fins educacionais

Saccharin and aspartame, compared with sucrose, induce greater weight gain in adult Wistar rats, at similar total caloric intake levels.

It has been suggested that the use of nonnutritive sweeteners (NNSs) can lead to weight gain, but evidence regarding their real effect in body weight and satiety is still inconclusive. Using a rat model, the present study compares the effect of saccharin and aspartame to sucrose in body weight gain and in caloric intake. Twenty-nine male Wistar rats received plain yogurt sweetened with 20% sucrose, 0.3% sodium saccharin or 0.4% aspartame, in addition to chow and water ad libitum, while physical activity was restrained. Measurements of cumulative body weight gain, total caloric intake, caloric intake of chow and caloric intake of sweetened yogurt were performed weekly for 12 weeks. Results showed that addition of either saccharin or aspartame to yogurt resulted in increased weight gain compared to addition of sucrose, however total caloric intake was similar among groups. In conclusion, greater weight gain was promoted by the use of saccharin or aspartame, compared with sucrose, and this weight gain was unrelated to caloric intake. We speculate that a decrease in energy expenditure or increase in fluid retention might be involved.

Time course of hydrogen peroxide-thioredoxin balance and its influence on the intracellular signalling in myocardial infarction.

We investigated the myocardial thioredoxin-1 and hydrogen peroxide concentrations and their association with some prosurvival and pro-apoptotic proteins, during the transition from myocardial infarction (MI) to heart failure in rats. Male Wistar rats were divided into the following six groups: three sham-operated groups and three MI groups, each at at 2, 7 and 28 days postsurgery. Cardiac function was analysed by echocardiography; the concentration of H(2)O(2) and the ratio of reduced to oxidized glutathione were measured spectrophotometrically, while the myocardial immunocontent of thioredoxin-1, angiotensin II, angiotensin II type 1 and type 2 receptors, p-JNK/JNK, p-ERK/ERK, p-Akt/Akt, p-mTOR/mTOR and p-GSK3ß/GSK3ß was evaluated by Western blot. Our results show that thioredoxin-1 appears to make an important contribution to the reduced H(2)O(2) concentration. It was associated with lower JNK expression in the early period post-MI (2 days). However, thioredoxin-1 decreased, while renin-angiotensin system markers and levels of H(2)O(2) increased, over 28 days post-MI, in parallel with some signalling proteins involved in maladaptative cardiac remodelling and ventricular dysfunction. These findings provide insight into the time course profile of endogenous antioxidant adaptation to ischaemic injury, which may be useful for the design of therapeutical strategies targeting oxidative stress post-MI.

Effects of dehydroepiandrosterone (DHEA) and lactate on glucose uptake in the central nervous system.

Dehydroepiandrosterone (DHEA) prevents brain aging, enhances the cerebral metabolism and interacts with energy substrates. The interaction between lactate and DHEA on glucose uptake and lactate oxidation by various nervous structures was investigated and results demonstrate that the 2-(14)C-deoxiglucose (2-(14)C-Dglucose) uptake was stimulated by 10mM lactate in the hypothalamus and olfactory bulb, inhibited in the cerebral cortex and cerebellum, and unaffected in the hippocampus. We also show that, in both the cerebral cortex and hypothalamus, (14)C-lactate oxidation was higher than (14)C-glucose oxidation (p≤0.001), demonstrating a relevant role for lactate as energy substrate. The interaction of lactate and 10(-8)M DHEA was tested and, although DHEA had no significant effect on uptake in the cerebellum, hippocampus, or hypothalamus, 10(-8)M DHEA increased the 2-(14)C-Dglucose uptake in the cerebral cortex in the presence of lactate (p≤0.001), and in the olfactory bulb in the absence of lactate (p<0.05). However, DHEA had no significant effect on (14)C-lactate oxidation. We suggest that DHEA improves glucose uptake in specific conditions. Thus, DHEA may affect CNS metabolism and interact with lactate, which is the most important neuronal energy substrate, on glucose uptake.

Dehydroepiandrosterone improves hepatic antioxidant reserve and stimulates Akt signaling in young and old rats.

This study examined, in the liver of young and old (3- and 24-month-old, respectively) healthy Wistar rats, the in vivo effect of dehydroepiandrosterone (DHEA) (10mg/kg body weight) administered subcutaneously for 5 weeks. Reduced (GSH) and oxidized (GSSG) glutathione levels, glucose-6-phosphate dehydrogenase (G6PDH), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) activities, hydrogen peroxide concentration, GST and p-Akt/Akt immunocontent ratio were assessed in hepatic tissue. DHEA treatment significantly increased total glutathione content (17%) and GSH (22%) in 3- and 24-month-old treated groups when compared to control groups. The aging factor increased G6PDH (51%) and GPx (22%) activities as well as the hydrogen peroxide concentration (33%), independently of treatment. DHEA treatment increased p-Akt (54%) and p-Akt/Akt ratio (36%) immunocontents in both treated groups. Increased serum levels of alanine aminotransferase (ALT) in aged rats were reduced by DHEA treatment (34%).

The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats.

Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor ß(1) (TGF-ß(1)) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-ß(1), as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-ß(1) and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood.

Redox imbalance influence in the myocardial Akt activation in aged rats treated with DHEA.

This study examined, in young and old (3 and 24 month-old, respectively) healthy Wistar rats, the in vivo effect of DHEA (10 mg/kg body weight) administered subcutaneously for 5 weeks. Reduced (GSH) and oxidized (GSSG) glutathione levels, glucose-6-phosphate dehydrogenase (G6PDH), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and thioredoxin (Trx) reductase activities, hydrogen peroxide steady-state concentration and Nrf2, GST, Trx-1, Akt and p-Akt expressions were assessed in heart tissue. DHEA treatment significantly increased GST activity in 3 and 24 month-old treated groups. The aging factor diminished hydrogen peroxide concentration and Nrf2 expression, independently of treatment. However, the aging process increased GST, Akt and p-Akt expressions in both 24 month-old groups. The aged group responded differently to DHEA respective to GSSG content, GPx activity and p-Akt concentration. Further studies are needed to form conclusions about the efficacy and safety of DHEA replacement in the elderly, and to better understand DHEA's net effect on oxidative stress parameters and its modulation of signaling cascades.