Consistent gut bacterial and short-chain fatty acid signatures in hypoabsorptive bariatric surgeries correlate with metabolic benefits in rats.

OBJECTIVE: The study aimed at comparing how changes in the gut microbiota are associated to the beneficial effects of the most clinically efficient hypoabsorptive bariatric procedures, namely Roux-en-Y gastric bypass (RYGB), biliopancreatic diversion with duodenal switch (BPD-DS) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S). METHODS: Diet-induced obese (DIO) male Wistar rats were divided into seven groups. In addition to the groups subjected to RYGB, BPD-DS and SADI-S, the following four control groups were included: SHAM-operated rats fed a high-fat diet (SHAM HF), SHAM fed a low-fat diet (SHAM LF), SHAM HF-pair-weighed to BPD-DS (SHAM HF-PW) and sleeve-gastrectomy (SG) rats. Body weight, food intake, glucose tolerance, insulin sensitivity/resistance, and L-cell secretion were assessed. The gut microbiota (16 S ribosomal RNA gene sequencing) as well as the fecal and cæcal contents of short-chain fatty acids (SCFAs) were also analyzed prior to, and after the surgeries. RESULTS: The present study demonstrates the beneficial effect of RYGB, BPD-DS and SADI-S on fat mass gain and glucose metabolism in DIO rats. These benefits were proportional to the effect of the surgeries on food digestibility (BPD-DS > SADI-S > RYGB). Notably, hypoabsorptive surgeries led to consonant microbial signatures characterized by decreased abundance of the Ruminococcaceae (Oscillospira and Ruminococcus), Oscillospiraceae (Oscillibacter) and Christensenellaceae, and increased abundance of the Clostridiaceae (Clostridium), Sutterellaceae (Sutterella) and Enterobacteriaceae. The gut bacteria following hypoabsorptive surgeries were associated with higher fecal levels of propionate, butyrate, isobutyrate and isovalerate. Increases in the fecal SCFAs were in turn positively and strongly correlated with the levels of peptide tyrosine-tyrosine (PYY) and with the beneficial effects of the surgery. CONCLUSION: The present study emphasizes the consistency with which the three major hypoabsorptive bariatric procedures RYGB, BPD-DS and SADI-S create a gut microbial environment capable of producing a SCFA profile favorable to the secretion of PYY and to beneficial metabolic effects.

Gestational exposure to Δ9-THC impacts ovarian follicular dynamics and angiogenesis in adulthood in Wistar rats.

With the legalization of marijuana (Cannabis sativa) and increasing use during pregnancy, it is important to understand its impact on exposed offspring. Specifically, the effects of Δ-9-tetrahydrocannabinol (Δ9-THC), the major psychoactive component of cannabis, on fetal ovarian development and long-term reproductive health are not fully understood. The aim of this study was to assess the effect of prenatal exposure to Δ9-THC on ovarian health in adult rat offspring. At 6 months of age, Δ9-THC-exposed offspring had accelerated folliculogenesis with apparent follicular development arrest, but no persistent effects on circulating steroid levels. Ovaries from Δ9-THC-exposed offspring had reduced blood vessel density in association with decreased expression of the pro-angiogenic factor VEGF and its receptor VEGFR-2, as well as an increase in the anti-angiogenic factor thrombospondin 1 (TSP-1). Collectively, these data suggest that exposure to Δ9-THC during pregnancy alters follicular dynamics during postnatal life, which may have long-lasting detrimental effects on female reproductive health.

Efeito do ômega 3 e da vitamina B12 no espermograma, na histomorfometria dos órgãos reprodutivos e nas temperaturas do corpo com termografia infravermelha em ratos Wistar / Effect of Omega 3 and Vitamin B12 on the spermogram, histomorphometry of the reproductive organs and body temperatures with infrared thermography in Wistar rats

Objetivou-se estudar o efeito do ômega 3 e da vitamina B12 no espermograma, na histomorfometria dos órgãos reprodutivos e na temperaturas do corpo com termografia infravermelha em ratos Wistar. Utilizaram-se 16 ratos, em quatro grupos (n=4), que receberam injeções diárias por 30 dias, sendo: grupo controle - solução salina; grupo ômega 3 - óleo de peixe 1g/kg; grupo B12 - vitamina B12 3µg; e grupo ômega 3 + B12 - óleo de peixe 1g/kg e vitamina B12 3µg. Imagens termográficas de áreas do corpo foram obtidas. No 30º dia, os ratos foram sacrificados e realizaram-se as análises de morfologia espermática e histomorfometria. Os dados foram submetidos à análise de variância e ao teste de Tukey a 5%. A temperatura da superfície do escroto foi superior no grupo B12 (P<0,05). Não houve diferenças entre grupos (P>0,05) para temperaturas do globo ocular. Houve correlação entre temperatura da superfície do escroto e porcentagem de gota citoplasmática distal (P=0,678). A elevação da temperatura do escroto resulta no aumento da porcentagem de gotas citoplasmáticas distais. A temperatura do globo ocular não sofre influência significativa do ômega 3 e da vitamina B12. O ômega 3 reduz o epitélio seminífero, e a vitamina B12 minimiza esse efeito.(AU)

The objective of this study was to study the effect of Omega 3 and vitamin B12 on spermogram, histomorphometry of reproductive organs and body temperature with infrared thermography in Wistar rats. Sixteen rats were used in four groups (n= 4) who received daily injections for 30 days. Control Group - saline solution; Group Omega 3 - fish oil 1g/kg; Group B12 - vitamin B12 3μg and Group Omega 3 + B12 - fish oil 1g/kg and vitamin B12 3μg. Thermographic images of body were obtained. On the 30th day the rats were sacrificed and analyzes of sperm morphology and histomorphometry were performed. Data were submitted to analysis of variance and Tukey's test at 5%. The surface temperature of the scrotum was higher in group B12 (P< 0.05). There were no differences between groups (P> 0.05) for eyeball temperatures. There was a correlation between scrotal temperature and distal cytoplasmic droplet (P= 0.678). Elevation of scrotum temperature results in an increase in the percentage of distal cytoplasmic droplets. The temperature of the eyeball is not significantly influenced by Omega 3 and vitamin B12. Omega 3 reduces the seminiferous epithelium and vitamin B12 minimizes this effect.(AU)

Diabetic cardiomyopathy: molecular mechanisms, detrimental effects of conventional treatment, and beneficial effects of natural therapy.

ABSTARCT: Diabetic complications are among the largely exigent health problems currently. Cardiovascular complications, including diabetic cardiomyopathy (DCM), account for more than 80% of diabetic deaths. Investigators are exploring new therapeutic targets to slow or abate diabetes because of the growing occurrence and augmented risk of deaths due to its complications. Research on rodent models of type 1 and type 2 diabetes mellitus, and the use of genetic engineering techniques in mice and rats have significantly sophisticated for our understanding of the molecular mechanisms in human DCM. DCM is featured by pathophysiological mechanisms that are hyperglycemia, insulin resistance, oxidative stress, left ventricular hypertrophy, damaged left ventricular systolic and diastolic functions, myocardial fibrosis, endothelial dysfunction, myocyte cell death, autophagy, and endoplasmic reticulum stress. A number of molecular and cellular pathways, such as cardiac ubiquitin proteasome system, FoxO transcription factors, hexosamine biosynthetic pathway, polyol pathway, protein kinase C signaling, NF-κB signaling, peroxisome proliferator-activated receptor signaling, Nrf2 pathway, mitogen-activated protein kinase pathway, and micro RNAs, play a major role in DCM. Currently, there are a few drugs for the management of DCM and some of them have considerable adverse effects. So, researchers are focusing on the natural products to ameliorate it. Hence, in this review, we discuss the pathogical, molecular, and cellular mechanisms of DCM; the current diagnostic methods and treatments; adverse effects of conventional treatment; and beneficial effects of natural product-based therapeutics, which may pave the way to new treatment strategies. Graphical Abstract.

Focal ischemic stroke leads to lung injury and reduces alveolar macrophage phagocytic capability in rats.

BACKGROUND: Ischemic stroke causes brain inflammation, which we postulate may result in lung damage. Several studies have focused on stroke-induced immunosuppression and lung infection; however, the possibility that strokes may trigger lung inflammation has been overlooked. We hypothesized that even focal ischemic stroke might induce acute systemic and pulmonary inflammation, thus altering respiratory parameters, lung tissue integrity, and alveolar macrophage behavior. METHODS: Forty-eight Wistar rats were randomly assigned to ischemic stroke (Stroke) or sham surgery (Sham). Lung function, histology, and inflammation in the lung, brain, bronchoalveolar lavage fluid (BALF), and circulating plasma were evaluated at 24 h. In vitro, alveolar macrophages from naïve rats (unstimulated) were exposed to serum or BALF from Sham or Stroke animals to elucidate possible mechanisms underlying alterations in alveolar macrophage phagocytic capability. Alveolar macrophages and epithelial and endothelial cells of Sham and Stroke animals were also isolated for evaluation of mRNA expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. RESULTS: Twenty-four hours following ischemic stroke, the tidal volume, expiratory time, and mean inspiratory flow were increased. Compared to Sham animals, the respiratory rate and duty cycle during spontaneous breathing were reduced, but this did not affect lung mechanics during mechanical ventilation. Lungs from Stroke animals showed clear evidence of increased diffuse alveolar damage, pulmonary edema, and inflammation markers. This was associated with an increase in ultrastructural damage, as evidenced by injury to type 2 pneumocytes and endothelial cells, cellular infiltration, and enlarged basement membrane thickness. Protein levels of proinflammatory mediators were documented in the lung, brain, and plasma (TNF-α and IL-6) and in BALF (TNF-α). The phagocytic ability of macrophages was significantly reduced. Unstimulated macrophages isolated from naïve rats only upregulated expression of TNF-α and IL-6 following exposure to serum from Stroke rats. Exposure to BALF from Stroke or Sham animals did not change alveolar macrophage behavior, or gene expression of TNF-α and IL-6. IL-6 expression was increased in macrophages and endothelial cells from Stroke animals. CONCLUSIONS: In rats, focal ischemic stroke is associated with brain-lung crosstalk, leading to increased pulmonary damage and inflammation, as well as reduced alveolar macrophage phagocytic capability, which seems to be promoted by systemic inflammation.

CCN3 secreted by prostaglandin E2 inhibits intimal cushion formation in the rat ductus arteriosus.

The ductus arteriosus (DA), an essential fetal shunt between the pulmonary trunk and the descending aorta, changes its structure during development. Our previous studies have demonstrated that prostaglandin E2 (PGE2)-EP4 signaling promotes intimal cushion formation (ICF) by activating the migration of DA smooth muscle cells via the secretion of hyaluronan. We hypothesized that, in addition to hyaluronan, PGE2 may secrete other proteins that also regulate vascular remodeling in the DA. In order to detect PGE2 stimulation-secreted proteins, we found that CCN3 protein was increased in the culture supernatant in the presence of PGE2 in a dose-dependent manner by nano-flow liquid chromatography coupled with tandem mass spectrometry analysis and enzyme-linked immunosorbent assay. Quantitative RT-PCR analysis revealed that PGE2 stimulation tended to increase the expression levels of CCN3 mRNA in DA smooth muscle cells. Immunohistochemical analysis revealed that CCN3 was highly localized in the entire smooth muscle layers and the endothelium of the DA. Furthermore, exogenous CCN3 inhibited PGE2-induced ICF in the ex vivo DA tissues. These results suggest that CCN3 is a secreted protein of the DA smooth muscle cells induced by PGE2 to suppress ICF of the DA. The present study indicates that CCN3 could be a novel negative regulator of ICF in the DA to fine-tune the PGE2-mediated DA remodeling.

Supplementation of grape seed and skin extract to orlistat therapy prevents high-fat diet-induced murine spleen lipotoxicity.

Spleen is the largest lymphoid organ and obesity is related to an elevated risk of immunity dysfunction. The mechanism whereby fat adversely affects the spleen is poorly understood. This study was designed to assess the effectiveness of grape seed and skin extract (GSSE) and orlistat (Xenical, Xe) on high-fat diet (HFD)-induced spleen lipotoxicity. Obese rats were treated either with GSSE (4 g/kg body weight) or Xe (2 mg/kg body weight) or GSSE+Xe and monitored for weight loss for 3 months. Animals were then sacrificed and their spleen used for the evaluation of lipotoxicity-induced oxidative stress and inflammation as well as the putative protection afforded by GSSE and Xe treatment. HFD induced body weight gain and glycogen accumulation into the spleen; ectopic deposition of cholesterol and triglycerides and an oxidative stress characterized by increased lipoperoxidation and carbonylation; inhibition of antioxidant enzyme activities, such as catalase, glutathione peroxidase, and superoxide dismutase; depletion of zinc and copper; and a concomitant increase in calcium. HFD also increased plasma pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17A, tumour necrosis factor alpha, and C-reactive protein, and decreased plasma IL-10 and adiponectin. Importantly, GSSE counteracted all the deleterious effects of HFD on spleen (i.e., lipotoxicity, oxidative stress, and inflammation) and the best protection was obtained when combining Xe+GSSE. Combining GSSE with Xe prevented against fat-induced spleen lipotoxicity, oxidative stress, and inflammation; this combination may be beneficial in other diseases related to the spleen.

Acute and chronic toxicity and antimicrobial activity of the extract of Stryphnodendron adstringens (Mart) Coville / Toxicidade aguda e crônica e atividade antimicrobiana do extrato de Stryphnodendron adstringens (Mart) Coville

This study evaluated the antimicrobial activity and acute or chronic toxicity of the extract of Stryphnodendron adstringens. The stem bark dry extract was obtained by static maceration with ethanol. Quantification of tannins was performed by the Folin-Denis method, which indicated a total tannin content of 32.7%. The antimicrobial activity of the dry extract of S. adstringens was evaluated by agar-based disk diffusion assay with Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923) in the concentration of 200, 400 and 600µL/mL. The results indicated that 600µL/mL inhibited microbial growth, i.e. had antimicrobial activity against these species. Acute and chronic toxic effects of S. adstringens was evaluated in Wistar rats treated with 200, 400, 600 and 800mg/kg of extract, administrated by gavage. Liver degeneration was observed in the group of rats receiving 800mg/kg in chronic exposure, what may indicate some degree of toxicity at this concentration. However, no systemic toxicity was observed at lower doses. Considering the broad use of S. adstringens as a phytotherapeutic agent for various human and animal diseases and the livertoxicity observed at high concentrations, attention should be paid to the possible adverse effect of using the extract from this plant at high concentration.(AU)

Avaliou-se neste estudo a atividade antimicrobiana e a toxicidades aguda e crônica do extrato da entrecasca de Stryphnodendron adstringens. A partir do extrato seco, obtido através da maceração estática da casca do caule em etanol de cereais, foi realizada a quantificação de taninos totais (32,7%) pelo método de Folin-Denis. A atividade antimicrobiana do extrato seco extraído de cascas do caule de S. adstringens foi avaliada pela técnica de disco-difusão para os micro-organismos Escherichia coli (ATCC 25922) e Staphylococcus aureus (ATCC 25923) nas concentrações de 200, 400 e 600µL/mL. Os testes de concentração inibitória mínima revelaram que 600µL/mL inibiu o crescimento dos dois micro-organismos testados; o mesmo resultado foi observado para atividade bactericida na concentração de 600µL/mL sobre essas espécies. Efeitos tóxicos sistêmicos agudos e crônicos do extrato seco de S. adstringens administrados por gavagem foram estudados em ratos Wistar, utilizando as doses de 400, 600 e 800mg/kg. Foi observada degeneração hepática no grupo de animais que receberam 800mg/kg tanto no estudo da toxicidade aguda quanto crônica, que pode indicar algum grau de toxicidade de S. adstringens nessa concentração. Considerando o amplo uso de S. adstringens como fitoterápico para humanos e animais, atenção deve ser dispensada para ingestão em altas doses mediante os efeitos tóxicos observados neste estudo.(AU)

Effects of Apigenin on Experimental Ischemia/Reperfusion Injury in the Rat Ovary.

BACKGROUND: Apigenin is a plant-derived compound belonging to the flavone class, which possess antioxidant, free-radical-scavenging and anti-inflammatory properties. AIMS: To address the effects of apigenin on serum anti-mullerian hormone levels, tissue oxidative stress parameters and histopathological changes in ovarian ischemia/reperfusion injury. STUDY DESIGN: Animal experiment. METHODS: Twenty-eight female Wistar albino rats were randomly separated into four sections: Sham operation (group 1), ischemia/reperfusion plus saline (group 2), ischemia/reperfusion plus dimethyl sulfoxide (group 3) and ischemia/reperfusion plus apigenin (group 4). In all ischemia/reperfusion groups, a bilateral adnexal 3-h period of ischemia was performed, followed by 3-h of reperfusion. A single dose of 15 mg/kg apigenin was given intraperitoneally 60 min before reperfusion in group 4. After 3-h of reperfusion, both ovaries were removed, and blood samples were collected. The main outcome measures were serum anti-mullerian hormone levels, ovarian tissue malondialdehyde, total nitric oxide, Cu/Zn superoxide dismutase, catalase and glutathione levels and histopathological damage scores. RESULTS: The ovarian tissue nitric oxide level was significantly lower, and the glutathione level was significantly higher in group 4 compared with groups 2 and 3. There was no significant difference in anti-mullerian hormone levels among the three ischemia/reperfusion groups. The histopathological damage score was lower in group 4 than in groups 2 and 3 (p>0.05). CONCLUSION: Administration of apigenin has no significant protective effect on ovarian reserve and tissue damage in ovarian ischemia/reperfusion injury.

Alterations in the hypothalamic­pituitary­thyroid axis in animals submitted to early-life trauma

Introduction: Changes in maternal care can affect offspring's thyroid hormone T3 levels. Pups from highly caring mothers have higher levels of thyroid hormone T3. In humans, physical abuse in childhood is related to lower levels of T3 in adolescence. This study aimed at verifying if early-life trauma in rodents is correlated with T3 levels in adulthood. Methods: From the second day of life, litters of Wistar rats were subjected to reduced nesting material (Early­Life Stress-ELS) or standard care (Controls). In adult life, the animals were chronically exposed to standard diet or standard diet + palatable diet and plasma T3 levels were measured before and after the exposition to diet. Results: Thyroid hormone T3 levels in adult life correlated negatively with the licking and grooming (LG) scores in the ELS group. This correlation disappeared when the animals had the opportunity to choose between two diets chronically. Conclusion: The adverse environment affected maternal behavior and caused marks on the metabolism of the intervention group (T3), which were reverted by chronic palatable food consumption (AU)

Starvation and refeeding in rats: effect on some parameters of energy metabolism and electrolytes and changes of hepatic tissue

Regarding the importance of starvation and refeeding and the occurrence of refeeding syndrome in various conditions, the present study was conducted to investigate the effects of refeeding on some parameters of energy metabolism and electrolytes and changes of hepatic tissue in male Wistar rats. Fifty-seven rats were divided into six groups, having 6 to 11 rats. Food was provided ad-libitum until three months and then the first group was considered without starvation (day 0). Other rats were fasted for two weeks. Group 2 was applied to a group immediately after starvation (day 14). Groups 3 to 6 were refed in days 16 till 22, respectively. At the end of each period, blood and tissue samples were taken and histopathological and serum analysis, including serum electrolytes (calcium, phosphorus, sodium, potassium), the energy parameters (glucose, insulin, cortisol) and the liver enzymes (ALT, AST, ALP) were determined. Insulin decreased by starvation and then showed an increasing trend compared to starvation period, which the highest amount of this parameter was observed eight days post-refeeding. Serum glucose level showed the opposite pattern of insulin. Histopathological examination of the tissue sections revealed clear vacuoles after starvation and refeeding, in which the severity of lesions gradually decreased during refeeding. The cortisol level decreased by starvation and then increased during refeeding. Also, potassium and phosphorus concentrations declined by refeeding and the serum sodium and potassium levels were changed in the relatively opposite manner. The calcium level decreased by starvation and then increased during refeeding. These results could help recognize and remedy the refeeding syndrome.(AU)

Reproductive toxicity of Samanea tubulosa on rats / Toxicidade reprodutiva de Samanea tubulosa em ratos

Samanea tubulosa is a plant used for medicinal and feeding purposes. However, ingestion of S. tubulosa pods has been associated with bovine abortion. Thus, the aim of this work was to investigate the effects of diet containing 5% of S. tubulosa pod meal on male and female Wistar rats. Diet was administered to male rats (n = 10) for 60 days before mating. Female rats (n = 10) received the treatment for 30 days, during cohabitation and from gestational day (GD) 0 to GD20. Treated animals were mated with untreated rats. In male rats, plant consumption caused decreased food consumption and 20% fertility index reduction. Litters from treated males presented lower body weight and crownrump length. Female rats treated with the plant increased water and food intake and body weight. Decreases in fertility, fecundity and gestation indices and increase of placenta weight and mean number of corpora lutea were found. Thus, owing to the possible general and reproductive toxic effects, long-term consumption of S. tubulosa is not recommended for phytotherapic or food purposes...

Samanea tubulosa é uma planta utilizada na fitoterapia e na alimentação animal. Entretanto, a ingestão de vagens de S. tubulosa tem sido associada à ocorrência de abortos em bovinos. Assim, o objetivo do trabalho foi investigar os efeitos da dieta contendo 5% de vagens de S. tubulosa em ratos machos e fêmeas Wistar. A dieta foi administrada para ratos machos (n = 10) por 60 dias antes do acasalamento. Ratos fêmeas (n = 10) receberam o tratamento por 30 dias, durante a coabitação e do dia gestacional (GD) 0 ao GD 20. As fêmeas tratadas foram acasaladas com ratos não tratados. Em machos, o consumo da planta causou diminuição no consumo de ração e redução de 20% no índice de fertilidade. A prole de machos tratados apresentou menor ganho de peso e comprimento cabeça cauda. Fêmeas tratadas com a planta apresentaram aumento do consumo de ração e água e do peso corporal. Ainda, foram observadas diminuição na fertilidade, fecundidade e no índice de gestação e aumento do peso da placenta e no número médio de corpos lúteos. Desse modo, em decorrência aos possíveis efeitos tóxicos sistêmicos e reprodutivos, o consumo prolongado de S. tubulosa não é recomendado para fins fitoterápicos ou alimentar...

Effects of perinatal period administration of clomiphene citrate in sexual behavior, organ weights and hormone concentration of Wistar male and female rats / Efeito da administração do citrato de clomifeno durante o período perinatal no comportamento sexual, peso dos órgãos e concentração hormonal de ratos Wistar machos e fêmeas

The effects of prenatal exposure to clomiphene citrate in sexual behavior, organ weight and hormone concentrations of male and female rats was evaluated. The animals received four doses of clomiphene citrate 2 mg/mL each during the prenatal period (21 days of gestation DG21) on days 1 (DN1), 2 (DN2) and 3 (DN3) after the birth of the puppies. The treatment led to the development of polycystic ovaries in 70% of the females, masculinization of female sexual behavior and changes in sexual behavior of males evidenced by the reduction in the number of ejaculations. In regards to hormone levels, a decrease in the FSH levels in male offspring was observed. It was concluded that clomiphene citrate interferes with the reproductive capacity of male and female rats and female sexual orientation when prenatally administered.

Foram investigados os efeitos da exposição perinatal ao citrato de clomifeno no comportamento sexual, peso dos órgãos e concentração hormonal de ratos machos e fêmeas. Os animais receberam quatro doses de 2 mg/mL de citrato de clomifeno, no período perinatal (21 dias de gestação DG21), nos dias 1 (DN1), 2 (DN2) e 3 (DN3) após o nascimento dos filhotes. O tratamento causou desenvolvimento de ovário policístico em 70% das fêmeas, masculinização do comportamento sexual das fêmeas e alteração do comportamento sexual dos machos evidenciado pela redução no número de ejaculações. Em relação aos níveis hormonais, observou-se diminuição de FSH na prole masculina. Concluiu-se que o citrato de clomifeno interfere na capacidade reprodutiva de ratos machos e fêmeas, e na orientação sexual de fêmeas, quando administrado perinatalmente.

Growth restriction in the rat alters expression of cardiac JAK/STAT genes in a sex-specific manner.

Uteroplacental insufficiency resulting in intrauterine growth restriction has been associated with the development of cardiovascular disease, coronary heart disease and increased blood pressure, particularly in males. The molecular mechanisms that result in the programming of these phenotypes are not clear. This study investigated the expression of cardiac JAK/STAT signalling genes in growth restricted offspring born small due to uteroplacental insufficiency. Bilateral uterine vessel ligation was performed on day 18 of pregnancy to induce growth restriction (Restricted) or sham surgery (Control). Cardiac tissue at embryonic day (E) 20, postnatal day (PN) 1, PN7 and PN35 in male and female Wistar (WKY) rats (n=7-10 per group per age) was isolated and mRNA extracted. In the heart, there was an effect of age for males for all genes examined there was a decrease in expression after PN1. With females, JAK2 expression was significantly reduced after E20, while PI3K in females was increased at E30 and PN35. Further, mRNA expression was significantly altered in JAK/STAT signalling targets in Restricteds in a sex-specific manner. Compared with Controls, in males, JAK2 and STAT3 were significantly reduced in the Restricted, while in females SOCS3 was significantly increased and PI3K significantly decreased in the Restricted offspring. Finally, there were specific differences in the levels of gene expression within the JAK/STAT pathway when comparing males to females. Thus, growth restriction alters specific targets in the JAK/STAT signalling pathway, with altered JAK2 and STAT3 potentially contributing to the increased risk of cardiovascular disease in the growth restricted males.

Cambios en la actividad de algunas enzimas séricas en ratas con hipervitaminosis E / Changes in activity of some serum enzymes in rats with hypervitaminosis E

Poco se sabe sobre los cambios en la actividad de las enzimas séricas relacionadas con la función hepática durante la hipervitaminosis E. En el presente trabajo se estudió el efecto de la administración intraperitoneal de 50, 100, 200 y 400 mg de vitamina E/día, durante 20 días sobre la actividad enzimática sérica en 60 ratas Wistar machos, de 12 semanas de edad, con pesos entre 180 y 200 gramos. El grupo control estuvo integrado por 15 ratas Wistar sanas, con edad y peso similares a los animales tratados. Al final del estudio, se tomaron muestras de sangre para la determinación de la vitamina E y la actividad de las enzimas: alanina aminotransferasa (ALT), aspartato aminotransferasa (AST), α-amilasa (AMS), arginasa (ARG), fosfohexosaisomerasa (PHI), fosfatasa alcalina (ALP), γ-glutamiltransferasa (γ-GT) y 5´-nucleotidasa (5´-N). La administración de vitamina E en exceso incrementó de manera significativa (p<0,05) el contenido sérico de la vitamina E y la actividad de todas las enzimas valoradas (p< 0,05); mientras que la α-amilasa disminuyó (p< 0,05) al ser comparada con los controles no tratados. Nuestros resultados proporcionan evidencia que la administración a corto plazo de dosis altas de vitamina E, produce un incremento en la actividad de las enzimas marcadoras de daño hepático (como aminotransferasas, ARG y PHI) y de colestasis (como ALP, 5´-N y γ-GT), que se corresponde con la forma mixta de enfermedad hepática (daño+colestasis).

Little is known about the possible changes in blood enzyme activity related to liver function during hypervitaminosis E. In the present work the effects of intraperitoneal administration of 50, 100, 200 and 400 mg of vitamin E (α-tocopherol) daily for 20 days, respectively, on the serum enzyme activity in 60 white male Wistar rats, aged 12 weeks and weighing 180-200 g, were studied. The group control was integrated by 15 healthy rats with similar characteristics (age and weight) to treated animals. Excess of vitamin E produced a significant (p<0.05) increase in the serum content of vitamin E and in the activity (p<0.05) of the following enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), arginase (ARG), phosphohexosaisomerase (PHI), alkaline phosphatase (ALP), γ-glutamyltransferase (γ-GT) and 5´-nucleotidase (5´-N) while α-amylase (AMS) decreased (p<0.05) on comparing with the control group. These changes depend on the doses given of vitamin E. In conclusion, our results provide evidence that short-term administration of high doses of vitamin E produces an increase in the activity of the enzymes marker of liver damage (as aminotransferases, ARG and PHI) and of cholestasis (as ALP, γ-GT and 5´-N) that correspond to the mixed form of liver disease (injury+cholestasis).

Influência da suplementação com creatina em indicadores de metabolismo da glucose no músculo esquelético de ratos exercitados / Influencia de la suplementación con creatina sobre indicadores del metabolismo de la glucosa en el músculo esquelético de ratas ejercitadas / Influence of creatine supplementation on indicators of glucose metabolism in skeletal muscle of exercised rats

The purpose of this study was to evaluate the effect of creatine supplementation in the diet on indicators of glucose metabolism in skeletal muscle of exercised rats. Forty Wistar adult rats were distributed into four groups for eight weeks: 1) Control: sedentary rats that received balanced diet; 2) Creatine control: sedentary rats that received supplementation of 2% creatine in the balanced diet; 3) Trained: rats that ran on a treadmill at the Maximal Lactate Steady State and received balanced diet; and 4) Supplemented-trained: rats that ran on a treadmill at the Maximal Lactate Steady State and received creatine supplementation (2%) in the balanced diet. The hydric intake increased and the body weight gain decreased in the supplemented-trained group. In the soleus muscle, the glucose oxidation increased in both supplemented groups. The production of lactate and glycemia during glucose tolerance test decreased in the supplemented-trained group. Creatine supplementation in conjunction with exercise training improved muscular glycidic metabolism of rats.

O objetivo deste estudo foi avaliar o efeito da suplementação de creatina na dieta sobre indicadores do metabolismo glicídico musculoesquelético de ratos exercitados. Quarenta ratos Wistar adultos foram divididos em quatro grupos por oito semanas: Controle: receberam dieta balanceada, mantidos sedentários; Controle Creatina: receberam suplementação de creatina (2%) na dieta balanceada, mantidos sedentários; Treinado: correram em esteira na intensidade da máxima fase estável de lactato e receberam a dieta balanceada e grupo Treinado Suplementado: correram em esteira na intensidade da máxima fase estável de lactato e receberam suplementação de creatina (2%) na dieta balanceada. A ingestão hídrica aumentou e o ganho de massa corporal reduziu no grupo treinado e suplementado. No músculo sóleo, a oxidação de glicose aumentou em ambos os grupos suplementados. A produção de lactato e a glicemia durante teste de tolerância à glicose diminuíram no grupo treinado e suplementado. A suplementação com creatina em conjunto com treinamento físico melhorou metabolismo de glicídico muscular dos ratos.

El objetivo de este estudio fue evaluar el efecto de la suplementación con creatina en la dieta sobre indicadores del metabolismo de glucosa en el músculo esquelético en ratones ejercitados. Cuarenta ratas macho adultas Wistar se dividieron en cuatro grupos de ocho semanas: Control: recibieron dieta equilibrada, mantenido sedentaria; Control Complementado: La suplementación con creatina recibido (2%) en la dieta equilibrada, sedentaria mantenido; Trained: corriendo en una cinta en la intensidad de máximo estado estable de lactato y recibió el grupo de dieta equilibrada y grupo Treinado Complementado: corriendo sobre una cinta rodante a una intensidad máxima de lactato estable y recibieron la suplementación con creatina (2%) en una dieta equilibrada. El consumo de agua aumenta y reducción de la ganancia de peso corporal en la formación y complementado. En el músculo sóleo, la oxidación de la glucosa aumentó en ambos grupos suplementados. La producción de los niveles de lactato y de glucosa durante la prueba de tolerancia a la glucosa disminuida en la formación y complementado. La suplementación con creatina en conjunto con el entrenamiento físico mejora el metabolismo de la glucosa en el músculo de los ratones.

Temperatura de polimerização da resina acrílica odontológica na medula espinhal de ratos Wistar / Polymerization temperature of dental acrylic resin in the spinal cord of rats

Objetivou-se investigar se a temperatura de polimerização da resina acrílica odontológica ocasiona sinais neurológicos e alteração histológica na medula espinhal de ratos. Foram utilizados 48 ratos, Wistar, distribuídos em dois grupos denominados GI ou cimento ósseo (controle positivo) e GII ou resina acrílica odontológica. Cada grupo foi redistribuído em seis subgrupos, de acordo com a quantidade do composto, o tempo de pós-operatório e o local de aferição da temperatura. O cimento ósseo ou a resina acrílica odontológica foram moldados e colocados sobre as lâminas ósseas dorsais e os processos espinhosos das vértebras L1 e L2. A temperatura de polimerização do composto foi aferida a cada 10 segundos. A temperatura máxima de polimerização e a diferença entre a temperatura externa e a interna ao canal vertebral foram maiores nos subgrupos que receberam 10 gramas. Não foi observada alteração neurológica em nenhum dos animais deste estudo. Na análise histológica, foi observada reação inflamatória de intensidade variável na meninge e no parênquima medular. Pode-se concluir que a temperatura de polimerização da resina acrílica odontológica nas quantidades de um e 10 gramas provoca alterações histológicas na meninge e no parênquima medular, sem ocasionar sinais neurológicos em ratos.

The purpose of this study was to evaluate if the polymerization temperature of the dental acrylic leads to neurological signs and histological changes in the rat spinal cord. Forty eight rats were distributed in two groups: GI or bone cement (positive control) and GII or dental acrylic resin. Each group was redistributed in six subgroups according to compound quantity, postoperative period and location of temperature measurement. The bone cement or dental acrylic resin were molded and positioned on the bony lamina and the dorsal spinous processes of vertebrae L1 and L2. The polimerization temperature was measured every 10 seconds. The polymerization maximum temperature and the temperature difference between internal and external spinal canals were superior in subgroups that received 10 grams. There were no neurological deficits in any animal of this study. The histological analysis showed intensity variation of inflammatory reaction in the meninges and spinal cord parenchyma. The results demonstrate that the polymerization temperature of dental acrylic resin in quantity of 1 or 10 grams causes histological changes in the spinal cord parenchyma and meninges, without neurological deficits in rats.

SHRSP/Izm and WKY/NCrlCrlj rats having a missense mutation in Abcg5 deposited plant sterols in the body, but did not change their biliary secretion and lymphatic absorption-comparison with Jcl:Wistar and WKY/Izm rats.

We had previously found plant sterols deposited in the bodies of stroke-prone spontaneously hypertensive rats (SHRSP)/Sea and Wistar Kyoto (WKY)/NCrlCrlj rats that had a missense mutation in the Abcg5 cDNA sequence that coded for ATP-binding cassette transporter (ABC) G5. We used SHRSP/Izm, WKY/NCrlCrlj, and WKY/Izm rats in the present study to determine the mechanisms for plant sterol deposition in the body. Jcl:Wistar rats were used as a control strain. A diet containing 0.5% plant sterols fed to the rats resulted in plant sterol deposition in the body of SHRSP/Izm, but not in WKY/Izm or Jcl:Wistar rats. Only a single non-synonymous nucleotide change, G1747T, resulting in a conservative cysteine substitution for glycine at amino acid 583 (Gly583Cys) in Abcg5 cDNA was identified in the SHRSP/Izm and WKY/NCrlCrlj rats. However, this mutation was not found in the WKY/Izm or Jcl:Wistar rats. No significant difference in the biliary secretion or lymphatic absorption of plant sterols was apparent between the rat strains with or without the missense mutation in Abcg5 cDNA. Our observations suggest that plant sterol deposition in rat strains with the missense mutation in Abcg5 cDNA can occur, despite there being no significant change in the biliary secretion or lymphatic absorption of plant sterols.

Efeito hipolipidêmico do suco de camu-camu em ratos / Hypolipidemic effect of camu-camu juice in rats

OBJETIVO: Este estudo teve como objetivo avaliar o potencial hipolipidêmico do suco de camu-camu (Myrciaria dubia (Kunth) McVaugh) em ratos dislipidêmicos. MÉTODOS: Foram utilizados 72 ratos (Rattus norvegicus var. albinus) machos adultos da linhagem Wistar, com peso médio de 200g. O experimento foi dividido em duas fases: indução da dislipidemia e tratamento. Para indução da dislipidemia, todos os ratos receberam ração hiperlipídica (ração comercial adicionada a 10,0% de banha suína, 1,0% colesterol e 0,1% de ácido cólico) durante 21 dias. Na fase de tratamento, 40 ratos dislipidêmicos foram divididos aleatoriamente em 5 grupos (n=8), sendo 3 deles submetidos a tratamento com diferentes concentrações de suco de camu-camu (0,4mL.kg-1, 4,0mL.kg-1 e 10mL.kg-1) por 14 dias, 1 grupo submetido a tratamento com quercetina (10mL.kg-1) e 1 grupo hiperlidêmico. Estes dois últimos foram mantidos como parâmetro, ao lado do grupo basal. Para avaliar o efeito modulador do suco de camu-camu no perfil lipídico dos ratos, foram verificadas as concentrações de triacilgliceróis, colesterol total, lipoproteína de alta intensidade e lipoproteína de baixa intensidade, no plasma, assim como os níveis de colesterol fecal e hepático.RESULTADOS: As diferentes doses de suco de camu-camu e de quercetina apresentaram efeitos moduladores do perfil lipídico, ou seja, redução de triacilgliceróis, colesterol total, excreção fecal de colesterol, bem como redução do colesterol hepático. Salienta-se que os melhores resultados foram obtidos com a concentração de 10mL.kg-1. Resultado similar foi observado quanto ao consumo de ração. CONCLUSÃO: O suco de camu-camu apresentou efeito modulador do perfil lipídico em ratos dislipidêmicos. Os resultados poderão ser utilizados como referência em futuros trabalhos acerca desse fruto amazônico.

OBJECTIVE: This study evaluated the potential hypolipidemic effect of camu-camu juice (Myrciaria dubia (Kunth) McVaugh) in dyslipidemic rats. METHODS: Seventy-two adult male Wistar rats (Rattus norvegicus var. albinus Berkenhout) with an average weight of 200g were used. The experiment was divided into two phases: induction of dyslipidemia and treatment. Dyslipidemia was induced by a high-fat diet (commercial feed plus 10.0% lard, 1.0% cholesterol and 0.1% cholic acid) given to the animals for 21 days. In the treatment phase, 40 dyslipidemic rats were randomly divided into five groups (n=8). Of these, three were subjected to different treatments with camu-camu juice: 0.4mL.kg-1, 4.0mL.kg-1 and 10mL.kg-1 for 14 days. The other two groups were kept as parameters: a basal group (normolipidemic) and a hyperlipidemic group receiving 10mL.kg-1 of quercetin (standard treatment). The potential hypolipidemic effect of camu-camu juice was assessed by the following measurements: plasma lipoproteins (triacylglycerol, total cholesterol, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol), fecal and liver cholesterol, and measurements of feed intake and body weight. RESULTS: All dosages of camu-camu juice were hypolipidemic, reducing triacylglycerol, total cholesterol, fecal cholesterol excretion and hepatic cholesterol. The best results were obtained by the 10 mL.kg-1 dosage of camu-camu juice. Rat body weight and food intake did not vary significantly during the treatment. CONCLUSION: Camu-camu juice has a hypolipidemic effect in dyslipidemic rats. These results can be used as reference for future studies on this Amazonian fruit.

Efeitos dos isômeros conjugados do ácido linoleico sobre a peroxidação lipídica em ratos / Effects of conjugated linoleic acid isomers on lipid peroxidation in rats

Ácidos graxos conjugados (AGCs) é o termo geral para descrever os isômeros posicionais e geométricos dos ácidos graxos poliinsaturados com duplas ligações conjugadas. Inúmeros efeitos benéficos para a saúde como: anti-cancerígeno, anti-aterogênicos, anti-adipogênicos e anti-inflamatórios, tem sido atribuídos ao consumo dos AGCs. Entretanto, estudos sobre os efeitos dos AGCs no organismo ainda são inconclusivos e por isso o interesse em pesquisas visando a sua participação em processos fisiológicos. O objetivo deste estudo foi avaliar em ratos o efeito dos isômeros conjugados do ácido linoleico (9cis, 11trans e 10trans, 12cis) sobre o perfil lipídico tecidual e sua influência sobre parâmetros bioquímicos em processos oxidativos. Não foi possível detectar a atividade antioxidante in vitro dos CLAs. Os resultados obtidos demonstraram que o FFA-CLA foi capaz de reagir apenas com o radical DPPH. No experimento in vivo uma mistura comercial dos isômeros (9cis, 11trans e 10trans, 12 cis) foi utilizada como fonte de CLAs, e a influência da suplementação desses isômeros, foi avaliada e comparada com um grupo controle suplementado com água e com grupos experimentais suplementados com óleo de soja. O primeiro experimento foi realizado com animais Wistar saudáveis e teve duração de 40 dias, as amostras de ácidos graxos livres de CLAs, (FFACLAs) e óleo de soja foram fornecidas aos animais por meio de entubação orogástrica nas concentrações de 1%, 2% e 4% em relação ao consumo diário de dieta, o grupo controle recebeu 1% de água. A suplementação da dieta dos animais com os CLAs leva ao aumento nos níveis de triglicérides, mas não interfere nos parâmetros de estresse oxidativo, embora haja incorporação dose-dependente nos tecidos hepático, muscular e adiposo, não foram observadas alterações no volume das células adiposas, e na área e diâmetro do tecido muscular. No segundo experimento, com duração de 21 dias, ao avaliar o efeito da suplementação na dose de 2% de CLAs em...

Conjugated fatty acids (CFAs) is the general term to describe positional and geometric isomers of polyunsaturated fatty acids with conjugated double bonds. Many beneficial health effects such as anti-cancer, anti-atherogenic, anti-adipogenic and anti-inflammatory, has been attributed to the consumption of the CFAs. However, studies on the effects of the CFAs in the body are still inconclusive and therefore the interest in research aimed at their participation in processes physiological. The objective of this study was to evaluate in rats the effect of conjugated linoleic acid isomers (9cis, 11trans and 10trans, 12cis) on lipid profile tissue and its effect on biochemical parameters in oxidative processes. It was not possible to detect the in vitro antioxidant activity of CLAs. The results showed that the free fatty acids of CLAs (FFA-CLAs) was able to react only with the DPPH radical. In in vivo experiment a commercial mixture of isomers (9cis, 11trans and 10trans, 12cis) was used as a source of CLAs and the influence of supplementation of these isomers was evaluated and compared with a control group supplemented with water and experimental groups supplemented with soybean oil. The first experiment was conducted with healthy Wistar and lasted 40 days, samples of FFA-CLA and soybean oil were delivered to animals via orogastric intubation at concentrations of 1%, 2 % and 4% in relation to daily diet, the control group received 1% water. Supplementing the diet with CLAs leads to increased levels of triglycerides, but does not interfere with oxidative stress parameters, although there is a dose-dependent incorporation into liver tissue, muscle and fat, no changes were observed in the volume of fat cells, and in the area and diameter of muscle tissue. In the second experiment, lasting 21 days, to evaluate the effect of supplementation at a dose of 2% of CLAs in Wistar, tha peroxidation induced by treatment with carbon tetrachloride. Could be observed...