Combined effects of cyclosporin and nifedipine on gingival overgrowth in rats is not age dependent

Background: Cyclosporin A and nifedipine cause gingival overgrowth in rat, and the combined use of these drugs increases the overgrowth severity. Objective: The purpose of this study was to compare gingival overgrowth of rats of differents ages treated with cyclosporin A and nifedipine alone or given concurrently. Materials and methods: Rats 15, 30, 60 and 90 d old were treated with 10 mg/kg body weight of cyclosporin A and/or 50 mg/kg body weight of nifedipine in the chow. Results: Young rats showed evident gingival overgrowth with nifedipine, cyclosporin A, and cyclosporin A and nifedipine given concurrently. Adult rats did not show significant gingival alterations when treated with cyclosporin A and nifedipine alone. Nevertheless evident gingival overgrowth with alterations of the epithelium and connective tissue were observed when treated simultaneously with cyclosporin A and nifedipine. Conclusion: These results suggest that the combined effects of cyclosporin A and nifedipine on gingival overgrowth in rat is not age dependent.

Different stress biomarkers sensitivity during acute treadmill running exercise in rats

The level of stress during acute or chronic exercise is important since higher levels of stress may impair homeostasis. The adrenal gland is an essential stress-responsive organ involved in the hypothalamic-pituitary-adrenal axis. The aim of the study was to analyze the sensitivity of different stress biomarkers of the adrenal gland during acute treadmill running at different intensities. Adult rats performed three 25 min running tests at velocities of 15, 20 and 25 m/min, for determination of maximum lactate steady state (MLSS). After obtaining individual MLSS animals were assigned to two groups: M, sacrificed after 25 minutes of exercise at MLSS, and AM, sacrificed after exercise at 25% above MLSS. For comparison, a control group C was sacrificed at rest. Blood corticosterone concentrations, as well, adrenal gland cholesterol and ascorbic acid concentrations were used as biomarkers. Serum corticosterone concentrations were higher after exercise in both M (1802,74±700,42) and AM (2027,96±724,94) groups when compared C group (467,11±262,12), but were not different as a function of exercise intensity. No difference in adrenal ascorbic acid (M=2,37±0,66; AM=2,11±0,50 and C=2,54±0,53) and cholesterol (M=1,04±0,12; AM=0,91±0,31 and C=1,15±0,40) levels were observed when the three groups were compared. Serum corticosterone concentrations showed to be sensitive to acute treadmill exercise intensity. On the other hand, ascorbic acid and cholesterol concentrations in adrenal were biomarkers not adequate to evaluate exercise stress in rats.

Exercise training in the aerobic/anaerobic metabolic transition prevents glucose intolerance in alloxan-treated rats

Background: Ninety percent of cases of diabetes are of the slowly evolving non-insulin-dependent type, or Type 2 diabetes. Lack of exercise is regarded as one of the main causes of this disorder. In this study we analyzed the effects of physical exercise on glucose homeostasis in adult rats with type 2 diabetes induced by a neonatal injection of alloxan. Methods: Female Wistar rats aged 6 days were injected with either 250 mg/ kg of body weight of alloxan or citrate buffer 0.01 M (controls). After weaning, half of the animals in each group were subjected to physical training adjusted to meet the aerobic-anaerobic metabolic transition by swimming 1 h/day for 5 days a week with weight overloads. The necessary overload used was set and periodically readjusted for each rat through effort tests based on the maximal lactate steady state procedure. When aged 28, 60, 90, and 120 days, the rats underwent glucose tolerance tests (GTT) and their peripheral insulin sensitivity was evaluated using the HOMA index. Results: The area under the serum glucose curve obtained through GTT was always higher in alloxan-treated animals than in controls. A decrease in this area was observed in trained alloxan-treated rats at 90 and 120 days old compared with non-trained animals. At 90 days old the trained controls showed lower HOMA indices than the non-trained controls. Conclusion: Neonatal administration of alloxan induced a persistent glucose intolerance in all injected rats, which was successfully counteracted by physical training in the aerobic/anaerobic metabolic transition. © 2008 Mota et al; licensee BioMed Central Ltd.

Gestational protein restriction induces CA3 dendritic atrophy in dorsal hippocampal neurons but does not alter learning and memory performance in adult offspring

Studies have demonstrated that nutrient deficiency during pregnancy or in early postnatal life results in structural abnormalities in the offspring hippocampus and in cognitive impairment. In an attempt to analyze whether gestational protein restriction might induce learning and memory impairments associated with structural changes in the hippocampus, we carried out a detailed morphometric analysis of the hippocampus of male adult rats together with the behavioral characterization of these animals in the Morris water maze (MWM). Our results demonstrate that gestational protein restriction leads to a decrease in total basal dendritic length and in the number of intersections of CA3 pyramidal neurons whereas the cytoarchitecture of CA1 and dentate gyrus remained unchanged. Despite presenting significant structural rearrangements, we did not observe impairments in the MWM test. Considering the clear dissociation between the behavioral profile and the hippocampus neuronal changes, the functional significance of dendritic remodeling in fetal processing remains undisclosed. © 2012 ISDN.

Glucose homoeostasis in rats exposed to acute intermittent hypoxia

Aim: Chronic exposure to intermittent hypoxia commonly induces the activation of sympathetic tonus and the disruption of glucose homoeostasis. However, the effects of exposure to acute intermittent hypoxia (AIH) on glucose homoeostasis are not yet fully elucidated. Herein, we evaluated parameters related to glucose metabolism in rats exposed to AIH. Methods: Male adult rats were submitted to 10 episodes of hypoxia (6% O2, for 45 s) interspersed with 5-min intervals of normoxia (21%), while the control (CTL) group was kept in normoxia. Results: Acute intermittent hypoxia rats presented higher fasting glycaemia, normal insulinaemia, increased lactataemia and similar serum lipid levels, compared to controls (n = 10, P < 0.05). Additionally, AIH rats exhibited increased glucose tolerance (GT) (n = 10, P < 0.05) and augmented insulin sensitivity (IS) (n = 10, P < 0.05). The p-Akt/Akt protein ratio was increased in the muscle, but not in the liver and adipose tissue of AIH rats (n = 6, P < 0.05). The elevated glycaemia in AIH rats was associated with a reduction in the hepatic glycogen content (n = 10, P < 0.05). Moreover, the AIH-induced increase in blood glucose concentration, as well as reduced hepatic glycogen content, was prevented by prior systemic administration of the β-adrenergic antagonist (P < 0.05). The effects of AIH on glycaemia and Akt phosphorylation were transient and not observed after 60 min. Conclusions: We suggest that AIH induces an increase in blood glucose concentration as a result of hepatic glycogenolysis recruitment through sympathetic activation. The augmentation of GT and IS might be attributed, at least in part, to increased β-adrenergic sympathetic stimulation and Akt protein activation in skeletal muscles, leading to a higher glucose availability and utilization. © 2013 Scandinavian Physiological Society.

Influence of creatine supplementation on indicators of glucose metabolism in skeletal muscle of exercised rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Phox2b-expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Neonatally induced mild diabetes: influence on development, behavior and reproductive function of female Wistar rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Pancreatic Alpha-Cell Dysfunction Contributes to the Disruption of Glucose Homeostasis and Compensatory Insulin Hypersecretion in Glucocorticoid-Treated Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Obesogenic environment by excess of dietary fats in different phases of development reduces spermatic efficiency of wistar rats at adulthood: correlations with metabolic status

This study compares the impact of obesogenic environment (OE) in six different periods of development on sperm parameters and the testicular structure of adult rats and their correlations with sex steroid and metabolic scenario. Wistar rats were exposed to OE during gestation (O1), during gestation/lactation (O2), from weaning to adulthood (O3), from lactation to adulthood (O4), from gestation to sexual maturity (O5), and after sexual maturation (O6). OE was induced by a 20% fat diet, and control groups were fed a balanced diet (4% fat). Serum leptin levels and adiposity index indicate that all groups were obese, except for O1. Three progressive levels of impaired metabolic status were observed: O1 presented insulin resistance, O2 were insulin resistant and obese, and groups O3, O4, and O5 were insulin resistant, obese, and diabetic. These three levels of metabolic damage were proportional to the increase of leptin and decreased circulating testosterone. The impairment in the daily sperm production (DSP) paralleled these three levels of metabolic and hormonal damage being marginal in O1, increasing in O2, and being higher in groups O3, O4, O5, and O6. None of the OE periods affected the sperm transit time in the epididymis, and the lower sperm reserves were caused mainly by impaired DSP. In conclusion, OE during sexual maturation markedly reduces the DSP at adulthood in the rat. A severe reduction in the DSP also occurs in OE exposure during gestation/lactation but not in gestation, indicating that breast-feeding is a critical period for spermatogenic impairment under obesogenic conditions.

Cimetidine-induced Leydig cell apoptosis and reduced EG-VEGF (PK-1) immunoexpression in rats: evidence for the testicular vasculature atrophy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Gestational and lactational exposition to Di-N-butyl-phthalate (DBP) increases inflammation and preneoplastic lesions in prostate of wistar rats after carcinogenic N-methyl-N-nitrosourea (MNU) plus testosterone protocol

In the present study, it was evaluated the susceptibility of prostatic lesions in male adult rats exposed to Di-N-butyl-phthalate during fetal and lactational periods and submitted to MNU plus testosterone carcinogenesis protocol. Pregnant females were distributed into four experimental groups: CN (negative control); CMNU (MNU control); TDBP100 (100 mg/kg of DBP); TDBP500 (500 mg/kg of DBP). Females from the TDBP groups received DBP, by gavage, from gestation day 15 (GD15) to postnatal day 21 (DPN21), while C animals received the vehicle (corn oil). CMNU, TDBP100, and TDBP500 groups received a single intraperitoneal injection of MNU (50 mg/kg) on the sixth postnatal week. After that, testosterone cypionate was administered subcutaneously two times a week (2 mg/kg) for 24 weeks. The animals were euthanized on PND220. Distal segment fragments of the ventral (VP) and dorsolateral prostate (DLP) were fixed and processed for histopathological analysis. Protein extracts from ventral prostate were obtained, and western blotting was performed to AR, ERα, MAPK (ERK1/2), and pan-AKT. Stereological analysis showed an increase in the epithelial compartment in TDBP100 and TDBP500 compared to CN. In general, there was increase in the incidence of inflammation and metaplasia/dysplasia in the DBP-treated groups, mainly in DLP, compared to CN and CMNU. Proliferation index was significant higher in TDBP500 and PIN (prostatic intraepithelial neoplasia) was more frequent in this group compared to CMNU. Western blot assays showed an increase in the expressions of AR and MAPK (ERK1/2) in the TDBP100 compared to CN, and ERα and AKT expressions were higher in the TDBP500 group compared do CN. These results showed that different doses of DBP during prostate organogenesis in Wistar rats could increase the incidence of premalignant lesions in initiated rats inducing distinct biological responses in the adulthood. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015.

Administração experimental de esteróide anabólico androgênico e álcool causa alterações histológicas e morfométricas nos ovários e útero de ratas adultas

Abusive and indiscriminate use of androgenic anabolic steroid is an usual practice among youth and adults of both sex. Usually these substances were utilized simultaneously with others drugs, licit or not, that causes damage to health. The purpose of study was to evaluate the influence of experimental administration of nandrolone decanoate steroid (ND), associated or not to alcohol, in the ovaries and uterus of adult rats. Females with regular estrous cycle (n = 20), were distributed in the groups: a) control (physiological solution); b) ND (7.5 mg/kg BW; intraperitoneal); c) alcohol (0.2 mL/100g BW; oral); d) ND + AL. The teatments were realized by single dose per week, during twelve consecutive weeks. The ovaries of rats in the groups ND, AL and ND + AL presented intense follicular atresia and decrease in the number of antral follicles and corpora lutea. None treatment did affect ovarian weight, but uterine weight was increase (p<0.05) in the ND + AL group. There were alterations in the uterine histology and morphometry at function of each treatment. Isolated or simultaneous use of anabolic steroid and alcohol promotes ovarian and uterine toxicity in adult female rats.

Efeitos do exercício aeróbio no músculo esquelético de ratos expostos à fumaça de cigarro

INTRODUÇÃO: Os fumantes sofrem redução da massa muscular e da resistência à fadiga e possivelmente a prática de atividade física contribua positivamente neste quadro. OBJETIVO: Este estudo teve por objetivo analisar as adaptações da musculatura esquelética frente à interação da prática de atividade física e exposição à fumaça de cigarro. MÉTODOS: 32 ratos machos foram divididos em grupos expostos à fumaça de cigarro, exercitados (G1) e sedentários (G3), e não expostos à fumaça, exercitados (G2) e sedentários (G4). A exposição à fumaça foi realizada mediante combustão de 10 cigarros em uma câmara de inalação durante 30 minutos, duas vezes ao dia, cinco dias por semana, durante 15 dias; o exercício aeróbio foi composto por sessões diárias de 60 minutos de caminhada em esteira, cinco dias por semana. Após o sacrifício, o músculo sóleo foi coletado e seus cortes foram corados pela técnica de HE e submetidos ao método histoquímico NADH-TR. RESULTADOS: O grupo G1 apresentou maior quantidade de alterações musculares, bem como ausência de atividade enzimática, o mesmo ocorrendo no G3, porém com menor intensidade; no G2 foi observado padrão normal para fibras exercitadas, estando as fibras do G4 preservadas. Quanto à morfometria, houve diferença significante para o fator exercício (p = 0,007), enquanto não foram observadas diferenças significantes para o fator exposição à fumaça (p = 0,668) e para a interação exposição à fumaça e exercício (p = 0,077). CONCLUSÃO: A interação entre inalação de fumaça de cigarro e exercício, realizada durante 15 dias em ratos machos Wistar adultos, acentuou as alterações histológicas do músculo sóleo, levando a uma alteração da atividade enzimática e acarretando em aumento do diâmetro das fibras musculares

Repeated predictable or unpredictable stress: effects on cocaine-induced locomotion and cyclic AMP-dependent protein kinase activity

Stressful experiences appear to have a strong influence on susceptibility to drug taking behavior. Cross-sensitization between stress and drug-induced locomotor response has been found. Locomotor response to novelty or cocaine (10 mg/kg, i.p.), cyclic AMP-dependent protein kinase (PKA) activity in the nucleus accumbens and basal corticosterone levels were evaluated in male adult rats exposed to acute and chronic predictable or unpredictable stress. Rats exposed to a 14-day predictable stress showed increased locomotor response to novelty and to cocaine, whereas rats exposed to chronic unpredictable stress demonstrated increased cyclic AMP-dependent PKA activity in the nucleus accumbens. Both predictable and unpredictable stress increased basal corticosterone plasma levels. These experiments demonstrated that stress-induced early cocaine sensitization depends on the stress regime and is apparently dissociated from stress-induced changes in cyclic AMP-dependent PKA activity and corticosterone levels. (C) 2002 Elsevier B.V. B.V. All rights reserved.