Avaliação de gastrocitoproteção, mecanismo de ação e comparação do efeito da vitamina E (α-Tocoferol) nas formas natural e sintética

The aim of this study was to verify if α-tocopherol, the main substance of Vitamin E and also the one with the major antioxidant propriety, could offer citoprotection to a stomach damaged by alcohol. There are many forms of α-tocopherol, two forms of them were evaluated; d-l-α-tocopherol, the synthetic form and d-α-tocopherol, the natural form of α-tocopherol. Three experiments were made, all of them having absolute ethanol as the lesion agent, but the period and the doses changed in each of them. In the first two experiments, each group of animals received a different form of α-tocopherol and in the third experiment, they’ve received α-tocopherol p.o. for the period of seven days before the lesion agent was administrated. Moreover, immunohistochemistry assays were made from the stomachs samples of the third experiment to verify possible mechanisms involving nitric oxide and 2-cyclooxygenase. Satisfactory results of citoprotection have been obtained when the two forms were administered in the period of one week at doses of 100 mg/kg for synthetic form and 150 mg/kg for natural type. Nevertheless, the two forms didn’t differ statistically in their effectiveness against ethanol. The immunohistochemistry assays showed an increase of the levels of NO and COX2 in relation with the negative control, although there was no correlation between this increase and the gastroprotective effect. In conclusion, α-tocopherol has gastroprotection effect in some doses, but apparently there is no such a thing like the better the dose, the better the effect; that citoprotection don’t have a relationship with NO neither with COX2; the natural and the synthetic form don’t differ in their gastroprotection effect. More studies must be done looking forward an effective dose and also to understand the mechanisms underlay the citoprotection of α-tocopherol in the stomach

Quantificação imunofenotípica de células T reguladoras em cães acometidos por linfoma multicêntrico submetidos ao protocolo quimioterápico chop associado ou não a um firocoxib

Pós-graduação em Medicina Veterinária - FCAV

Efeitos da dose única de parecoxibe sobre a morte celular em rins de ratos submetidos à hemorragia aguda

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

Vias de sinalização endotelial α2, AT1, e AT2 sobre a reatividade da aorta de ratos após consumo de etanol e exposição ao estresse, isoladamente e em associação

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effects of exercise training on stress-induced vascular reactivity alterations: role of nitric oxide and prostanoids

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

Efeitos preventivos do treinamento físico na expressão das proteínas Cox-2 e Vegf de ratos tratados com dexametasona

Dexamethasone is a synthetic glucocorticoid widely used to treat allergic and inflammatory processes. This drug is used in three main situations, are used to contain acute or chronic inflammatory processes, or like immunosuppressive drug's. In these cases the patient will receive high doses for a chronic period and, therefore, has a much greater chance of adverse side effects, such as hypertension, diabetes and dyslipidemia. Dexamethasone promotes deleterious effects on the arachidonic acid pathway, when administered in high doses, because it is a potent anti-inflammatory drug. We recently demonstrated that dexamethasone significantly reduces the protein expression of vascular endothelial growth factor (VEGF) in both skeletal muscle and heart, but the mechanisms involved remain unclear. Meanwhile, exercise has been shown to be effective against high blood pressure, diabetes and dyslipidemia, promoting, among other factors, the increase in VEGF and angiogenesis. One possible explanation for these effects would be the creation of new vessels mediated by inflammation, or by the stimulation of the formation of products of the metabolism of arachidonic acid (AA), such as prostaglandin E2 (PGE2) and VEGF, by increasing the stimulation of the enzymes cyclooxygenase 1 and 2 (COX-1 and COX-2). Little is known about the preventive effects of training on the action of dexamethasone in the arachidonic acid pathway. Therefore, the aim of this study was to determine whether aerobic exercise training, performed before and concomitant treatment with dexamethasone, was able to prevent the effects of the dexamethasone in the protein expression of COX-2 and VEGF. For this, we used young Wistar rats (n = 40) which were randomly divided into 4 groups: sedentary control (SC), sedentary and treated with dexamethasone (SD), trained control (TC) and trained and treated with dexamethasone (TD). These rats performed aerobic exercise training, 60% of maximum capacity, 5

Efeitos preventivos do exercício físico sobre as proteínas ciclooxigenase-2 (COX-2) e fator de crescimento de vasos derivado do endotélio (VEGF) no músculo cardíaco em ratos tratados com dexametasona

Dexamethasone (DEXA) is a synthetic glucocorticoid widely used in the handling of several drugs, for its proven benefits in fighting inflammation and allergies. Despite their benefits, their chronic use leads to several side effects that include changes in the body in the metabolism of carbohydrates, lipids and proteins. Moreover, being an anti-inflammatory, acts on the arachidonic acid pathway, reducing the expression of the enzyme cyclooxygenase (COX-2) and growth factor derived from the endothelium of blood vessels (VEGF) in various tissues. However, its effects on the myocardium are still uncertain. The physical training (PT), in turn, promotes effects contrary to those caused by chronic use of DEXA, however, little is known about the preventive effects of TF in the side effects of Dexa in the myocardium. Therefore, the aim of this study was to determine if the TF has the ability to prevent and/or mitigate the effects of Dexa in protein expression of COX-2 and VEGF in the myocardium. Forty animals were divided into 4 groups: sedentary control (SC), sedentary treated with Dexa (SD), trained control (TC) and Trained treated with Dexa (TD) and submitted to a protocol of physical training on the treadmill for 70 days (1 h/day-5 days per week, 60% of physical capacity) or kept sedentary. Over the past 10 days, rats were treated with Dexa (Decadron, 0.5 mg/kg per day, ip) or saline. During training the animals were weighed weekly and during treatment daily. At the end of treatment was made to measure fasting glucose levels of animals. The rats were killed with excess anesthesia and cardiac muscle was removed, weighed, homogenized, centrifuged and stored at -20° C for analysis of protein expression of VEGF and COX-2 by Western blotting technique. Treatment with dexamethasone caused a weight loss of 18% in sedentary animals and 13% in trained as well as elevated levels of fasting glucose in sedentary (88%). The TF was unable to mitigate the loss in...

Effects of electroacupuncture on experimental periodontitis in rats

Background: Acupuncture has shown the capability of modulating the immuno-inflammatory response of the host. This study aims to evaluate the effects of electroacupuncture (EA) on ligature-induced periodontitis in rats. Methods: Thirty-two animals were divided into four groups: 1) control; 2) experimental periodontitis (EP); 3) sham-treated (EP/EA-sham); and 4) treated with EA (EP/EA). For the EP groups, a ligature was placed around the right mandibular first molars at day 1. Sessions of EA or EA-sham were assigned every other day. For EA treatment, large intestine meridian points LI4 and LI11 and stomach meridian points ST36 and ST44 were used. EA-sham was performed in off-meridian points. Animals were euthanized at day 11. Histomorphometric and microtomographic analyses were performed. Immunolabeling patterns for the receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRAP) were assessed. Expressions of interleukin (IL)-1 beta, matrix metalloproteinase (MMP)-8, IL-6, and cyclooxygenase (COX)-2 messenger RNAs (mRNAs) were evaluated by quantitative reverse transcription-polymerase chain reaction. Data were analyzed statistically (P < 0.05, analysis of variance). Results: Histomorphometric and microtomographic analyses demonstrated that group EP/EA presented reduced alveolar bone loss when compared to group EP (P < 0.05). Reduced RANKL immunolabeling and fewer TRAP-positive multinucleated cells were observed in the EA-treated group in relation to group EP. No differences were observed in OPG expression among groups. EA treatment decreased the genic expression of IL-1 beta and MMP-8 (P < 0.05), increased the mRNA expression of IL-6 (P < 0.05), and did not modify the genic expression of COX-2 in animals with EP (P > 0.05). Conclusion: It can be concluded that EA reduced periodontal tissue breakdown and the expression of some proinflammatory mediators and a proresorptive factor in EP in rats.

Protective effects of the galectin-1 protein on in vivo and in vitro models of ocular inflammation

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

Evaluation of prognostic factors and survival rates in malignant feline mammary gland neoplasms

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

Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-Acyl hydrazone subunit

A series of anti-inflammatory derivatives containing an N-acyl hydrazone subunit (4a–e) were synthesized and characterized. Docking studies were performed that suggest that compounds 4a–e bind to cyclooxygenase (COX)-1 and COX-2 isoforms, but with higher affinity for COX-2. The compounds display similar anti-inflammatory activities in vivo, although compound 4c is the most effective compound for inhibiting rat paw edema, with a reduction in the extent of inflammation of 35.9% and 52.8% at 2 and 4 h, respectively. The anti-inflammatory activity of N-acyl hydrazone derivatives was inferior to their respective parent drugs, except for compound 4c after 5 h. Ulcerogenic studies revealed that compounds 4a–e are less gastrotoxic than the respective parent drug. Compounds 4b–e demonstrated mucosal damage comparable to celecoxib. The in vivo analgesic activities of the compounds are higher than the respective parent drug for compounds 4a–b and 4d–e. Compound 4a was more active than dipyrone in reducing acetic-acid-induced abdominal constrictions. Our results indicate that compounds 4a–e are anti-inflammatory and analgesic compounds with reduced gastrotoxicity compared to their respective parent non-steroidal anti-inflammatory drugs.

Endothelium dependent expression and underlying mechanisms of des-Arg(9)-bradykinin-induced B1R-mediated vasoconstriction in rat portal vein

Endothelial dysfunction has been implicated in portal vein obstruction, a condition responsible for major complications in chronic portal hypertension. Increased vascular tone due to disruption of endothelial function has been associated with an imbalance in the equilibrium between endothelium-derived relaxing and contracting factors. Herein, we assessed underlying mechanisms by which expression of bradykinin B-1 receptor (B1R) is induced in the endothelium and how its stimulation triggers vasoconstriction in the rat portal vein. Prolonged in vitro incubation of portal vein resulted in time- and endothelium-dependent expression of B1R and cyclooxygenase-2 (COX-2). Inhibition of protein kinase C (PKC) or phosphatidylinositol 3-kinase (PI3K) significantly reduced expression of B1R through the regulation of transcription factors, activator protein-1 (AP-1) and cAMP response element-binding protein (CREB). Moreover, pharmacological studies showed that B1R-mediated portal vein contraction was reduced by COX-2, but not COX-1, inhibitors. Notably, activation of endothelial B1R increased phospholipase A(2)/COX-2-derived thromboxane A(2) (TXA(2)) levels, which in turn mediated portal vein contraction through binding to TXA(2) receptors expressed in vascular smooth muscle cells. These results provide novel molecular mechanisms involved in the regulation of B1R expression and identify a critical role for the endothelial B1R in the modulation of portal vein vascular tone. Our study suggests a potential role for B1R antagonists as therapeutic tools for diseases where portal hypertension may be involved. (C) 2012 Elsevier Inc. All rights reserved.

Involvement of PGE(2) and RANTES in Staphylococcus aureus-induced fever in rats

Martins JM, Longhi-Balbinot DT, Soares DM, Figueiredo MJ, Malvar D do C, de Melo MC, Rae GA, Souza GE. Involvement of PGE(2) and RANTES in Staphylococcus aureus-induced fever in rats. J Appl Physiol 113: 1456-1465, 2012. First published August 30, 2012; doi:10.1152/japplphysiol.00936.2011.-This study investigated the involvement of prostaglandins and regulated on activation, normal T cell expressed and secreted (RANTES), in fever induced by live Staphylococcus aureus (no. 25923, American Type Culture Collection) injection in rats. S. aureus was injected intraperitoneally at 10(9), 10(10), and 2 x 10(10) colony-forming units (CFU)/cavity, and body temperature (T-b) was measured by radiotelemetry. The lowest dose of S. aureus induced a modest transient increase in T-b, whereas the two higher doses promoted similar long-lasting and sustained T-b increases. Thus, the 10(10) CFU/cavity dose was chosen for the remaining experiments. The T-b increase induced by S. aureus was accompanied by significant decreases in tail skin temperature and increases in PGE(2) levels in the cerebrospinal fluid (CSF) and hypothalamus but not in the venous plasma. Celecoxib (selective cyclooxygenase-2 inhibitor, 2.5 mg/kg po) inhibited the fever and the increases in PGE(2) concentration in the CSF and hypothalamus induced by S. aureus. Dipyrone (120 mg/kg ip) reduced the fever from 2.5 to 4 h and the PGE(2) increase in the CSF but not in the hypothalamus. S. aureus increased RANTES in the peritoneal exudate but not in the CSF or hypothalamus. Met-RANTES (100 mu g/kg iv), a chemokine (C-C motif) receptor (CCR)1/CCR5 antagonist, reduced the first 6 h of fever induced by S. aureus. This study suggests that peripheral (local) RANTES and central PGE(2) production are key events in the febrile response to live S. aureus injection. As dipyrone does not reduce PGE(2) synthesis in the hypothalamus, it is plausible that S. aureus induces fever, in part, via a dipyrone-sensitive PGE(2)-independent pathway.

High-fat diet causes an imbalance in the colonic serotonergic system promoting adipose tissue enlargement and dysplasia in rats

A high-fat (HF) diet, the serotonergic system and stromal elements have all been implicated in colon carcinogenesis. We investigated whether the colonic serotonergic system could play a main role in the development of colonic dysplasia and stromal reactivity in carcinogen-treated rats under HF diet. For this, dimethylhydrazine-treated rats were fed with standard diet and a HF diet. Fat distribution was quantified by computerized tomography exam, serotonergic activity was analyzed by high-performance liquid chromatography, gene expression, and immunohistochemistry, which along with histopathological technique enabled us to enumerate dysplasia, microvessels density, cell proliferation and COX-2 expression. We found that the HF diet induced an increase in the amount of viscera! adipose tissue, even without expressive changes in the average body weight. This was correlated with a loss of serotonergic balance in colon tissue. Moreover, the HF diet promoted dysplasia and microvessel density in association with increased proliferation and COX-2 expression within pericryptal colonic stroma. Our current findings suggest that a HF diet promotes the enlargement of adipose tissue via loss of control in colon serotonergic activity, which enhances colonic dysplasia by supporting microvessel development. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Synthesis, anti-inflammatory activity and molecular docking studies of 2,5-diarylfuran amino acid derivatives

A series of 2,5-diaryl substituted furans functionalized with several amino acids were synthesized and evaluated as the cyclooxygenases COX-1 and COX-2 enzymes inhibitors. The proline-substituted compound inhibited PGE(2) secretion by LPS-stimulated neutrophils, suggesting selectivity for COX-2. Molecular docking studies in the binding site of COX-2 were performed. (C) 2011 Elsevier Masson SAS. All rights reserved.