The role of indomethacin and tezosentan on renal effects induced by Bothrops moojeni Lys49 myotoxin I

Renal changes determined by Lys49 myotoxin I (BmTx I), isolated from Bothrops moojeni are well known. The scope of the present study was to investigate the possible mechanisms involved in the production of these effects by using indomethacin (10 mu g/mL), a non-selective inhibitor of cyclooxygenase, and tezosentan (10 mu g/mL), an endothelin antagonist. By means of the method of mesenteric vascular bed, it has been observed that B. moojeni myotoxin (5 mu g/mL) affects neither basal perfusion pressure nor phenylephrine-preconstricted vessels. This fact suggests that the increase in renal perfusion pressure and in renal vascular resistance did not occur by a direct effect on renal vasculature. Isolated kidneys from Wistar rats, weighing 240-280 g, were perfused with Krebs-Henseleit solution. The infusion of BmTx-I increased perfusion pressure, renal vascular resistance, urinary flow and glomerular filtration rate. Sodium, potassium and chloride tubular transport was reduced after addition of BmTx-I. Indomethacin blocked the effects induced by BmTx-I on perfusion pressure and renal vascular resistance, however, it did not revert the effect on urinary flow and sodium, potassium and chloride tubular transport. The alterations of glomerular filtration rate were inhibited only at 90 min of perfusion. The partial blockade exerted by indomethacin treatment showed that prostaglandins could have been important mediators of BmTx-I renal effects, but the participation of other substances cannot be excluded.The blockage of all renal alterations observed after tezosentan treatment support the hypothesis that endothelin is the major substance involved in the renal pathophysiologic alterations promoted by the Lys49 PLA(2) myotoxin I, isolated from B. moojeni. In conclusion, the rather intense renal effects promoted by B. moojeni myotoxin-I were probably caused by the release of renal endothelin, interfering with the renal parameters studied. (c) 2006 Elsevier Ltd. All rights reserved.

Ooplast-mediated developmental rescue of bovine oocytes exposed to ethidium bromide

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

The maspin expression in canine mammary tumors: an immunohistochemical and molecular study

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

Longevity of Oncidium varicosum (Orchidaceae) inflorescences treated with 1-methylciclopropene

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

Diapocynin versus apocynin as pretranscriptional inhibitors of NADPH oxidase and cytokine production by peripheral blood mononuclear cells

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

The oxidation of apocynin catalyzed by myeloperoxidase: Proposal for NADPH oxidase inhibition

Apocynin has been used as an efficient inhibitor of the NADPH oxidase complex and its mechanism of inhibition is linked to prior activation through the action of peroxidascs. Here we studied the oxidation of apocynin catalyzed by myeloperoxidase (MPO) and activated neutrophils. We found that apocynin is easily oxidized by MPO/H2O2 or activated neutrophils and has as products dimer and trimer derivatives. Since apocynin impedes the migration of the cytosolic component p47phox to the membrane and this effect could be related to its conjugation with essential thiol groups, we studied the reactivity of apocynin and its MPO-catalyzed oxidation products with glutathione (GSH). We found that apocynin and its oxidation products do not react with GSH. However, this thiol compound was efficiently oxidized by the apocynin radical during the MPO-catalyzed oxidation. We suggest that the reactivity of apocynin radical with thiol compounds could be involved in the inhibitory effect of this methoxy-catechol on NADPH oxidase complex. (c) 2006 Elsevier B.V. All rights reserved.

Fruit of the jambolan tree (Eugenia jambolana Lam.) and experimental diabetes

The fruit of Indian Eugenia jambolana have been shown to have therapeutic properties, but because the therapeutic potential of a plant is related to the geographic region in which the plant was grown and to the part of the plant used, we investigated Brazilian Eugenia jambolana fruit using the same preparation and experimental methods as have been used in India. The well-established metabolic cage model was used to evaluate the physiological and metabolic parameters associated with streptozotocin-induced diabetes in rats (n = 10) which had been administered, by gavage, 50 mg per day of lyophilised Eugenia jambolana fruit-pulp extract for 41 days. We found that, compared to untreated controls, rats treated with the lyophilised fruit-pulp showed no observable difference in body weight, food or water intake, urine volume, glycaemia, urinary urea and glucose, hepatic glycogen, or on serum levels of total cholesterol, HDL cholesterol or triglycerides. No change was observed in the masses of epididymal or retroperitoneal adipose tissue or of soleus or extensor digitorum longus muscles. This lack of any apparent effect on the diabetes may be attributable to the regional ecosystem where the fruit was collected and/or to the severity of the induced diabetes. (C) 2004 Elsevier B.V.. All rights reserved.

Effects of isocoumarins isolated from Paepalanthus bromelioides on mitochondria: Uncoupling, and induction/inhibition of mitochondrial permeability transition

Isolated mitochondria may undergo uncoupling, and in presence of Ca2+ at different conditions, a mitochondrial permeability transition (MPT) linked to protein,thiol oxidation, and demonstrated by CsA-sensitive mitochondrial swelling; these processes may cause cell death either by necrosis or by apoptosis. Isocoumarins isolated from the Brazilian plant Paepalanthus bromelioides (Eriocaulaceae) paepalantine (9,10-dihydroxy-5,7-dimethoxy-1H-naptho(2,3c)pyran-1-one), 8,8'-paepalantine dimer, and vioxanthin were assayed at 1-50 mu M on isolated rat liver mitochondria, for respiration, MPT, protein thiol oxidation, and interaction with the mitochondrial membrane using 1,6-diphenyl-1,3,5-hexatriene (DPH). The isocoumarins did not significantly affect state 3 respiration of succinate-energized mitochondria; they did however, stimulate 4 respiration, indicating mitochondrial uncoupling. Induction of MPT and protein thiol oxidation were assessed in succinate-energized mitochondria exposed to 10 mu M Ca2+; inhibition of these processes was assessed in non-energized organelles in the presence of 300 mu M t-butyl hydroperoxide plus 500 mu M Ca2+. Only paepalantine was an effective MPT/protein thiol oxidation inducer, also releasing cytochrome c from mitochondria; the protein thiol oxidation, unlike mitochondrial swelling, was neither inhibited by CsA nor dependent on the presence of Ca2+. Vioxanthin was an effective inhibitor of MPT/protein thiol oxidation. All isocoumarins inserted deeply into the mitochondrial membrane, but only paepalantine dimer and vioxantin decreased the membrane's fluidity. A direct reaction with mitochondrial membrane protein thiols, involving an oxidation of these groups, is proposed to account for MPT induction by paepalantine, while a restriction of oxidation of these same thiol groups imposed by the decrease of membrane fluidity, is proposed to account for MPT inhibition by vioxanthin. (c) 2006 Published by Elsevier B.V..

Review of Fluconazole Properties and Analytical Methods for Its Determination

Fluconazole, alpha-(2.4-diflurofenil)-alpha-(1H-triazol-1-methyl)-1H-1,2,4-triazol-1-ethanol, is an antifungal of the triazoles class. It shows activity against species of Candida sp. and it is indicated in cases of oropharyngeal candidiasis, esophageal, vaginal, and deep infection. Fluconazole is a selective inhibitor of ergosterol, a steroid exclusive of the cell membrane of fungal cells. Fluconazole is highly absorbed by the gastrointestinal tract and spreads easily by body fluids. The main adverse reactions related to the use of fluconazole are nausea, vomiting, headache, rash, abdominal pain, diarrhea, and alopecia in patients undergoing prolonged treatment with a dose of 400 mg/day. In the form of raw material, pharmaceutical formulations, or biological material, fluconazole can be determined by methods such as titration, spectrophotometry, and thin-layer, gas, and liquid chromatography. This article discusses the pharmacological and physicochemical properties of fluconazole and also the methods of analysis applied to the determination of the drug.

Effect of Glycolic Extract of Dillenia indica L. Combined With Microcurrent Stimulation on Experimental Lesions in Wistar Rats

This study evaluated the wound healing activity of a glycolic extract of Dillenia indica (GED) prepared from the mature fruits of the plant applied alone or in combination with microcurrent stimulation to skin wounds surgically induced on the back of Wistar rats. Methods. The animals were randomly divided into six groups: (A) negative control group; (B) group receiving microcurrent application (MC; [10 mu A/2 mins]); (C) group treated with GED; (D) group treated with an emulsion containing GED; (E) group treated with GED and MC, and (F) group treated with the emulsion containing GED and MC. Tissue samples were obtained 2, 6, and 10 days after injury and underwent structural and morphometric analysis, Results. There were observed differences in wound healing among the various treatments when compared to the control group. The combination of microcurrent plus extract or microcurrent plus emulsion containing GED was advantageous in all of the studied parameters (P < 0.05) when compared to the other groups with positive effects seen regarding newly formed tissue, number of fibroblasts, and number of newly formed blood vessels. The morphometric data confirmed the structural findings. Conclusion. Microcurrent application alone or combined with GED exerted significant effects on wound healing in this experimental model. This was probably due to the efficacy of microcurrent application since the extract alone did not significantly accelerate the healing process. D indica fruit extract most likely participates in the wound healing process as a result of its anti-inflammatory properties.

Antitumor and immunomodulatory effects of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin

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

Experimental murine mycobacteriosis: evaluation of the functional activity of alveolar macrophages in thalidomide- treated mice

Thalidomide is a selective inhibitor of tumor necrosis factor-alpha (TNF-alpha), a cytokine involved in mycobacterial death mechanisms. We investigated the role of this drug in the functional activity of alveolar macrophages in the presence of infection induced by intranasal inoculation of Mycobacterium avium in thalidomide-treated and untreated adult Swiss mice. Sixty animals were inoculated with 5 x 10(6) M. avium by the respiratory route. Thirty animals received daily thalidomide (30 mg/kg mouse) and 30 received water by gavage up to sacrifice. Ten non-inoculated mice were used as a control group. Lots of animals from each group were evaluated until 6 weeks after inoculation. Infection resulted in an increased total number of inflammatory cells as well as increased activity of pulmonary macrophages. Histologically, intranasal inoculation of bacilli resulted in small mononuclear infiltrates located at the periphery of the organ. Culture of lung fragments revealed the presence of bacilli only at the beginning and at the end of the experimental period. Thalidomide administration did not affect the microbiological or histological features of the infection. Thalidomide-treated and untreated animals showed the same amount of M. avium colonies 3 weeks after infection. Although it did not affect bacillary clearance, thalidomide administration resulted in a decreased percent of spread cells and release of hydrogen peroxide, suggesting that factors other than TNF-alpha play a role in the killing of mycobacteria by alveolar macrophages. Thalidomide administration also reduced the number of spread cells among resident macrophages, suggesting a direct effect of the drug on this phenomenon.