Avaliação do estresse oxidativo no sangue e na placenta de ratas com diabete de intensidade moderada

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The dorsal raphe nucleus exerts opposed control on generalized anxiety and panic-related defensive responses in rats

It has been proposed that the ascending dorsal raphe (DR)-serotonergic (5-HT) pathway facilitates conditioned avoidance responses to potential or distal threat, while the DR-periventricular 5-HT pathway inhibits unconditioned flight reactions to proximal danger. Dysfunction on these pathways would be, respectively, related to generalized anxiety (GAD) and panic disorder (PD). To investigate this hypothesis, we microinjected into the rat DR the benzodiazepine inverse receptor agonist FG 7142, the 5-HT1A receptor agonist 8-OH-DPAT or the GABA(A) receptor agonist muscimol. Animals were evaluated in the elevated T-maze (ETM) and light/dark transition test. These models generate defensive responses that have been related to GAD and PD. Experiments were also conducted in the ETM 14 days after the selective lesion of DR serotonergic neurons by 5,7-dihydroxytriptamine (DHT). In all cases, rats were pre-exposed to one of the open arms of the ETM 1 day before testing. The results showed that FG 7142 facilitated inhibitory avoidance, an anxiogenic effect, while impairing one-way escape, an anxiolytic effect. 8-OH-DPAT, muscimol, and 5,7-DHT-induced lesions acted in the opposite direction, impairing inhibitory avoidance while facilitating one-way escape from the open arm. In the light/dark transition, 8-OH-DPAT and muscimol increased the time spent in the lighted compartment, an anxiolytic effect. The data supports the view that distinct DR-5-HT pathways regulate neural mechanisms underlying GAD and PD. (C) 2002 Elsevier B.V. B.V. All rights reserved.

Nandrolone Decanoate and Physical Effort: Histological and Morphometrical Assessment in Adult Rat Uterus

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

Effects of Statin and Aerobic Physical Exercise Association in the Cardiomyocytes of the Rat. Morphometric Study

Physical exercise and statins, recommended interventions to dyslipidaemia treatment, are independently related to cardiomyocytes alterations, characterized by miocardic hypertrophy and apoptosis, respectively. Thus, the objective of the present study was to analyze the effects of statin and aerobic physical exercise association in the morphometric parameters of cardiac cell nucleus. 40 male rats adults were divided into four groups: exercised (DE); sedentary (DS), exercised and statin use (DES); sedentary and statin use (DSS). The animals received during the whole experimental period a hiperlipidic diet added 20% of coconut oil and 1.25% of cholesterol; after 30 days of its ingestion, a blood collection was made to verify the dyslipidaemia. Simvastatin (20 mg) was taken five days a week, during eight weeks. During this period, the animals exercised 60 minutes daily in the treadmill. After the last day of the protocol, the cardiac muscle was collected and maintained in liquid nitrogen (-180 degrees C); the cuts were stained by Hematoxilin-Eosin method, and the cardiac fibers were submitted to the nuclear morphometric analyses. The data were analyzed using descriptive analyses, paired T test, Kruskal-Wallis test and Dunn post hoc test; for all analyses, it was adopted p<0.05. It was verified that the group receiving statin presented values statistically significant in comparison to the other groups, in the tridimensional and linear variables. The exercised and statin group, the values obtained in the morphometric analyses were similar to the control group. It is suggested that statins alone can cause alterations in the nucleus of cardiac cells that can be related to apoptosis occurrence and, when exercise is practiced associated to statin administration, the effects of statin can be reduced, what can be related to beneficial adaptations of cardiac mitochondrial in response to physical exercise, turning them more resistant to apoptotic stimuli.

Effects of a ferment soy product on the adipocyte area reduction and dyslipidemia control in hypercholesterolemic adult male rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effects of a probiotic soy product and physical exercise on formation of pre-neoplastic lesions in rat colons in a short-term model of carcinogenic

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

Reversed phase HPLC determination of zidovudine in rat plasma and its pharmacokinetics after a single intranasal dose administration

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

Dexamethasone-induced insulin resistance is associated with increased connexin 36 mRNA and protein expression in pancreatic rat islets

Augmented glucose-stimulated insulin secretion (GSIS) is an adaptive mechanism exhibited by pancreatic islets from insulin-resistant animal models. Gap junction proteins have been proposed to contribute to islet function. As such, we investigated the expression of connexin 36 (Cx36), connexin 43 (Cx43), and the glucose transporter Glut2 at mRNA and protein levels in pancreatic islets of dexamethasone (DEX)-induced insulin-resistant rats. Study rats received daily injections of DEX (1 mg/kg body mass, i.p.) for 5 days, whereas control rats (CTL) received saline solution. DEX rats exhibited peripheral insulin resistance, as indicated by the significant postabsorptive insulin levels and by the constant rate for glucose disappearance (K-ITT). GSIS was significantly higher in DEX islets (1.8-fold in 16.7 mmol/L glucose vs. CTL, p < 0.05). A significant increase of 2.25-fold in islet area was observed in DEX vs. CTL islets (p < 0.05). Cx36 mRNA expression was significantly augmented, Cx43 diminished, and Glut2 mRNA was unaltered in islets of DEX vs. CTL (p < 0.05). Cx36 protein expression was 1.6-fold higher than that of CTL islets (p < 0.05). Glut2 protein expression was unaltered and Cx43 was not detected at the protein level. We conclude that DEX-induced insulin resistance is accompanied by increased GSIS and this may be associated with increase of Cx36 protein expression.

Endurance training stimulates growth and survival pathways and the redox balance in rat pancreatic islets

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

Rat model of depending prostaglandin renal state: Effect of ketoprofen

Introduction .The renal prostaglandins (PGs), vasodilators, preserve kidney function during increased activity of the renin-angiotensin system or renal sympathetic nerves (renal PG-dependent state [RPGD]). Ketoprofen (Ket) inhibits cyclooxygenase and, therefore, the synthesis of PGs. The aim of this study was to determine, in the rat, the action of Ket in the renal histology and function in a RPGD state (stress of anesthesia and hemorrhage). Material and Methods . Twenty male Wistar rats, anesthetized with sodium pentobarbital, were randomly divided into two groups: G1-control ( n = 10) and G2-Ket ( n = 10) submitted to arterial hemorrhage of 30% of volemia (estimated as 6% of body weight) three times (10% each 10 min), 65 min after anesthesia. G2 animals received Ket, 1.5 mg. kg -1 , venously, 5 min after anesthesia and 60 min before the first hemorrhage moment (first moment of the study [M1]). Medium arterial pressure (MAP), rectal temperature (T), and heart rate were monitored. G1 and G2 received para-aminohippurate sodium (PAH) and iothalamate sodium (IOT) solutions during the entire experimental time in order to determine clearance of PAH (effective renal plasma flow [ERPF]) and clearance of IOT (glomerular filtration rate [GFR]) without urine collection (determination of blood concentrations of PAH and IOT through the high-performance liquid chromatography), filtration fraction (FF), and renal vascular resistance (RVR). The animals were sacrificed in M3, 30 min after the third hemorrhage (M2) moment, and the kidneys and blood collected during the hemorrhage periods were utilized for histological study and determinations of hematocrit (Ht), serum creatinine (S Cr ), ERPF, GFR, FF, and RVR, respectively. Results . There were significant reductions of MAP, T, and Ht and a significant increase of S Cr . During the experiment, ERPF and GFR did not change, but ERPF was always higher in G1 than in G2. Ket did not alter FF, which increased in G1 over the duration of experiment. The Ket group had significantly higher RVR than the control group. The histology verified that both G1 and G2 were similar for tubular dilation and necrosis, but they were significantly different for tubular degeneration: G1 > G2. Conclusion . The changes observed in kidney histology probably were determined by hemorrhage and hypotension. Ket inhibited the synthesis of PGs and diminished tubular degeneration.

Diclofenac sodium and Imipenem action on rat intestinal mucosa: a biomechanical and histological study

OBJETIVO: Avaliar as alterações histológicas e biomecânicas do diclofenaco de sódio na mucosa intestinal do rato e a associação com o uso de Imipenem. MÉTODOS: Foram estudados 240 ratos Wistar distribuídos aleatoriamente em quatro grupos experimentais: GI: 60 ratos tratados com injeção IM de soro fisiológico 0,9%; GII: 60 ratos tratados com injeção IM de diclofenaco de sódio na dose de 6mg/kg de peso por 4 dias; GIII: 60 ratos tratados com injeção IM de Imipenem na dose de 30 mg/kg de peso por 4 dias; GIV: 60 ratos tratados com injeção IM de soro fisiológico e diclofenaco de sódio nas doses acima. em cada grupo os animais foram posteriormente divididos em 4 momentos de 15 animais em cada um para sacrifício, respectivamente, no 4º, 7º, 14º e 21º dias após o início do tratamento. As alterações da cavidade abdominal, assim como as características histológicas e de força de ruptura do intestino delgado foram analisadas em cada momento, em cada grupo. RESULTADOS: Não foram encontradas alterações histológicas e biomecânicas nos animais do Grupo I nesse estudo. Lesões ulceradas na mucosa do intestino delgado foram observadas nos animais tratados com diclofenaco de sódio, assim como diminuição da força de ruptura. As lesões ulceradas encontradas foram prevenidas pelo uso de Imipenem. CONCLUSÃO: O diclofenaco de sódio induz lesões ulceradas na mucosa intestinal do rato que podem ser prevenidas pelo uso de Imipenem.

No mutations found in exon 2 of gene p16CDKN2A during rat tongue carcinogenesis induced by 4-nitroquinoline-1-oxide

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

Evaluation of level of DNA damage in blood leukocytes of non-diabetic and diabetic rat exposed to cigarette smoke

The objective of the present study was to use the comet assay to evaluate the steady-state level of DNA damage in peripheral blood leukocytes from diabetic and non-diabetic female Wistar rats exposed to air or to cigarette smoke. A total of 20 rats were distributed into four experimental groups (n= 5 rats/group): non-diabetic (control) and diabetic exposed to filtered air; non-diabetic and diabetic exposed to cigarette smoke. A pancreatic beta (beta)-cytotoxic agent, streptozotocin (40 mg/kg b.w.) was used to induce experimental diabetes in rats. Rats placed into whole-body exposure chambers were exposed for 30 min to filtered air (control) or to tobacco smoke generated from 10 cigarettes, twice a day, for 2 months. At the end of the 2-month exposure period, each rat was anesthetized and humanely killed to obtain blood samples for genotoxicity analysis using the alkaline comet assay. Blood wleukocytes sampled from diabetic rats presented higher DNA damage values (tail moment =0.57 +/- 0.05; tail length =19.92 +/- 0.41, p < 0.05) compared to control rats (tail moment =0.34 +/- 0.02; tail length= 17.42 +/- 0.33). Non-diabetic (tail moment =0.43 +/- 0.04, p > 0.05) and diabetic rats (tail moment= 0.41 +/- 0.03, p > 0.05) exposed to cigarette smoke presented non-significant increases in DNA damage levels compared to control group. In conclusion, our data show that the exposure of diabetic rats to cigarette smoke produced no additional genotoxicity in peripheral blood cells of female Wistar rats. (c) 2007 Elsevier B.V. All rights reserved.

Effect of indomethacin on the pregnant rat

O objetivo deste trabalho foi avaliar a performance reprodutiva, estudo morfológico do fígado e característicapost mortem de ratas Wistar prenhes tratadas com indometacina, um inibidor geral de COX. Indometacina foi administrada oralmente, nas doses de 0 (controle), 0,32, 1,68 e 8,40 mg/kg/dia (n=10/grupo), nos dias 3 e 4 de prenhez (dia 0 = primeiro dia de prenhez = esperma positivo). Os animais foram eutanasiados sob anestesia no 11º dia de prenhez, e foram realizadas necropsia e cultura de microorganismos. Os resultados mostraram que as doses de 0,32 e 1,68 mg/kg de peso corpóreo (dose terapêutica para humanos) de indometacina não causaram efeitos embriotóxicos ou letais. A maior dose (8,40 mg/kg) de indometacina prejudicou o processo de implantação e, portanto, interferiu no desenvolvimento fetal. A peritonite foi detectada na necropsia e nos estudos bacteriológicos dos animais tratados com 8,4 mg/kg e considerada a causa-morte destes animais. Portanto, este estudo analisou um agente farmacológico na prenhez de roedores e evidenciou que a indometacina apresentou efeitos embriotóxicos e letais na maior dose empregada, mas foi segura na dose terapêutica usada pelo homem.

Chlorhexidine induces DNA damage in rat peripheral leukocytes and oral mucosal cells

Objective: Chlorhexidine digluconate is widely used in dental practice for decreasing plaque control, controlling gingivitis and disinfecting root canals. However, the undesirable effects of chlorhexidine digluconate regarding its genotoxicity are conflicting in the literature. Thus, the aim of this study was to investigate the genotoxicity of chlorhexidine digluconate in rat peripheral blood and oral mucosal cells by the single cell gel (comet) assay and micronucleus assay.Methods: Thirty male Wistar rats were distributed into three groups: negative control; experimental group orally treated with 0.5 ml of 0.12% chlorhexidine digluconate, twice daily, during 8 days; and positive control, which received 4-nitroquinoline 1-oxide at 0.5 g/l by drinking water.Results: A statistically significant increase of DNA damage was observed in leukocytes and oral mucosal cells of the chlorhexidine digluconate treated group, as assessed by the comet assay. However, no increase of micronucleated cells was detected in reticulocytes from peripheral blood cells.Conclusions: Taken together, the data indicate that chlorhexidine digluconate is able to induce primary DNA damage in leukocytes and in oral mucosal cells, but no chromosome breakage or loss in erythrocytes.