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ABSTRACT: Alginates isolated from Sargassum vulgare, present a strong antitumor activity, associated with kidney reversible damage, as analysed by histopathology of treated animals. In the present study, the renal alteration mechanisms of S. vulgare alginates were investigated using the isolated perfused rat kidney and the isolated perfused rat mesenteric blood vessel methods. The results showed that the effects of Sargassum vulgare low viscosity (SVLV) alginate were more potent than those of Sargassum vulgare high viscosity (SVHV) alginate in the isolated rat kidney. The SVLV alginate caused considerable changes in renal physiology, as shown by an increase in parameters such as perfusion pressure, renal vascular resistance, glomerular filtration rate, urinary flow and sodium, potassium and chloride excretion and by reduction of chloride tubular transport. The effects of SVHV were weaker than those of SVLV. The effects of SVLV on kidney could be related to direct vascular action as demonstrated with SVLV alginate on mesenteric blood vessels. In conclusion, the Sargassum vulgare alginate altered the renal function parameters evaluated. S. vulgare low viscosity alginate renal effects were more potent than S. vulgare high viscosity alginate. It is suggested that physicochemical differences between SVHV and SVLV could explain the differences found in the results.
Journal of Applied Toxicology 05/2008; 28(3):364-9. · 2.48 Impact Factor
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Marcus Davis Machado Braga,
Alice Maria Costa Martins,
Daniela Nascimento Amora,
Dalgimar Beserra de Menezes,
Marcos Hikari Toyama,
Daniela Oliveira Toyama,
Sergio Marangoni,
Claudênio Diógenes Alves,
Paulo Sérgio Ferreira Barbosa, Renata de Sousa Alves,
Manassés Claudino Fonteles,
Helena Serra Azul Monteiro
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ABSTRACT: Bothrops insularis is a snake from Ilha da Queimada Grande, an island located about 20 miles away from the Southeastern coast of Brazil. Compared with other Brazilian species of Bothrops, the toxinology of B. insularis is still poorly understood, and so far, no fraction from this venom with amino acid oxidase activity had been isolated or its biological activity tested. We investigated the biochemical and biological effects of one l-amino acid oxidase enzyme isolated from B. insularis snake venom (BiLAO), which was purified using HPLC and sequence grade. We also evaluated the renal effects induced by BiLAO. Chromatographic profile of B. insularis whole venom disclosed seven main fractions (I, II, III, IV, V, VI and VII) and the main LAO enzymatic activity was detected in fraction II. The group treated with BiLAO showed a decrease in perfusion pressure (C(120)=110.28+/-3.69; BiLAO(120)=82.2+/-5.6 mmHg*); renal vascular resistance (C(120)=5.48+/-0.53; BiLAO(120)=4.12+/-0.42 mmHg/mL/g/min*), urinary flow (C(120)=0.160+/-0.020; BiLAO(120)=0.064+/-0.012 mL/g/min*), glomerular filtration rate (C(120)=0.697+/-0.084; BiLAO(120)=0.176+/-0.017 mL/g/min*), sodium (C(120)=79.76+/-0.56; BiLAO(120)=65.39+/-6.19%*), potassium (C(120)=69.94+/-6.86; BiLAO(120)=60.26+/-2.24%*) and chloride tubular reabsortion (C(120)=78.53+/-2.33; BiLAO(120)=64.58+/-6.68%*). Acute tubular necrosis foci were observed in the group treated with the LAO fraction of the B. insularis snake venom. Some findings have the same morphological aspect of apoptosis, more evident cortically; otherwise, reversible degenerative phenomena represented by hydropic ballooning with extensive cytoplasmic vacuolization and discontinuity of the cell brush borders in the proximal tubular epithelium were observed; furthermore, necrotic detachment of these cells into the tubular lumina, and increased amount of protein deposits in the distal and proximal tubules were observed. In conclusion, the slowness of blood flow and of glomerular filtration resulted in more time for filtration and tubular reabsorption, with elevation of the total percentage of sodium and chlorine reabsorption. The maintenance of the decrease in glomerular filtration rate would determine the subsequent decreases, which were noticed in these parameters. The necrosis observed was the result of damage cell induced by l-amino acid oxidase isolated from B. insularis venom.
Toxicon 03/2008; 51(2):199-207. · 2.51 Impact Factor
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Marcus Davis Machado Braga,
Alice Maria Costa Martins,
Daniela Nascimento Amora,
Dalgimar Beserra de Menezes,
Marcos Hikari Toyama,
Daniela Oliveira Toyama,
Sergio Marangoni,
Paulo Sérgio Ferreira Barbosa, Renata de Sousa Alves,
Manassés Claudino Fonteles,
Helena Serra Azul Monteiro
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ABSTRACT: Bothrops insularis is a snake from Queimada Grande Island, which is an island located about 20 miles away from the southeastern coast of Brazil. Compared to other Brazilian species of Bothrops, the toxinology of B. insularis is still poorly understood. Its C-type lectin is involved in several biological processes including anticoagulant and platelet-modulating activities. We purified the C-type lectin (BiLec) from Bothrops insularis venom and investigated its effect in the isolated kidney. BiLec was purified after two chromatographic steps; firstly, the whole venom was submitted to an HPLC molecular exclusion chromatography followed by a second purification through affinity chromatography. B. insularis lectin (BiLec) was studied as to its effect on the renal function of isolated perfused rat kidneys with the use of six Wistar rats. The concentration of 10mug/mL increased perfusion pressure (PP; control(60)=108.27+/-4.9; BiLec(60)=112.9+/-5.4 mmHg; *p<0.05) and renal vascular resistance (RVR; control(60)=5.38+/-0.51; BiLec(60)=6.01+/-0.57 mmHg; *p<0.05). The urinary flow reduced significantly at 90 and 120 min of perfusion (UF; control(120)=0.160+/-0.020; BiLec(120)=0.082+/-0.008 mL g(-1) min(-1); *p<0.05). Glomerular filtration rate (GFR; control(120)=0.697+/-0.084; BiLec(120)=0.394+/-0.063 mL g(-1) min(-1); *p<0.05) diminished only at 120 min. BiLec did not change the percentage of sodium (TNa(+)), potassium (TK(+)) and chloride tubular transport (TCl(-)). The histological alterations probably reflected direct injury on glomerular and tubular renal cells, as demonstrated by the rise in permeability of glomerular endothelial cells, revealed by the presence of a proteinaceous material in the Bowman space. We postulate that the C-type lectin B. insularis promoted its effects probably through interactions with endothelial cells or through the release of other mediators by tubular, mesangial and endothelial cells.
Toxicon 06/2006; 47(8):859-67. · 2.51 Impact Factor
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Renata de Sousa Alves,
Nilberto Robson Falcão do Nascimento,
Paulo Sérgio Ferreira Barbosa,
Marta Regina Kerntopf,
Lucília Maria Abreu Lessa,
Clauber Mota de Sousa,
René Duarte Martins,
Daniel Freire Sousa,
Maria Goretti Rodrigues de Queiroz,
Marcos Hikari Toyama,
Manassés Claudino Fonteles,
Alice Maria Costa Martins,
Helena Serra Azul Monteiro
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ABSTRACT: Tityus serrulatus, popularly known as yellow scorpion, is one of the most studied scorpion species in South America and its venom has supplied some highly active molecules. The effects of T. serrulatus venom upon the renal physiology in human showed increased renal parameters, urea and creatinine. However, in perfused rat kidney the effects were not tested until now. Isolated kidneys from Wistar rats, weighing 240-280 g, were perfused with Krebs-Henseleit solution containing 6% (g weight) of previously dialysed bovine serum albumin. The effects of T. serrulatus venom were studied on the perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), sodium tubular transport (%TNa+), potassium tubular transport (%TK+) and chloride tubular transport (%TCl-). Tityus serrulatus venom (TsV; 10 microg/mL) was added to the system 30 min after the beginning of each experiment (n=6). This 30 min period was used as an internal control. The mesenteric bed was perfused with Krebs solution kept warm at 37 degrees C by a constant flow (4 mL/min), while the variable perfusion pressure was measured by means of a pressure transducer. The direct vascular effects of TsV (10 microg/mL/min; n=6), infused at a constant rate (0.1 mL/min), were examined and compared to the infusion of the vehicle alone at the same rate. TsV increased PP (PP30'=127.8+/-0.69 vs PP60'=154.2+/-14 mmHg*, *p<0.05) and RVR (RVR30'=6.29+/-0.25 vs RVR60'=8.03+/-0.82 mmHg/mLg(-1)min(-1)*, *p<0.05), decreased GFR (GFR30'=0.58+/-0.02 vs GFR60'=0.46+/-0.01mLg(-1)min(-1)*, *p<0.05) and UF (UF30'=0.135+/-0.001 vs UF60'=0.114+/-0.003mLg(-1)min(-1)*, *p<0.05). Tubular transport was not affected during the whole experimental period (120 min). On the other hand, the infusion of TsV (10 microg/mL/min) increased the basal perfusion pressure of isolated arteriolar mesenteric bed (basal pressure: 74.17+/-3.42 vs TsV 151.8+/-17.82 mmHg*, *p<0.05). TsV affects renal haemodynamics probably by a direct vasoconstrictor action leading to decreased renal flow.
Toxicon 10/2005; 46(3):271-6. · 2.51 Impact Factor
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ABSTRACT: Multiple risk factors for cardiovascular disorders, particularly hypercholesterolemia, are often present in hypertensive patients. Several studies have shown that antihypertensive drugs affect the lipid profile, increasing the risk of cardiovascular diseases. Here, it was investigated the lipoprotein metabolism alterations in a group of hypertensive patients in care by the Hypertension and Diabetes Program of a public hospital in Fortaleza-CE/Brazil. In this study, one hundred sixty nine serum samples from hypertensive patients (32-87 years old) under antihypertensive therapy were analyzed. Triglycerides, total cholesterol, cholesterol from high density lipoprotein (HDL) and from low density lipoprotein (LDL) serum levels were determined by enzymatic colorimetric method and AI and B apolipoproteins by immunoturbidimetric assay. The population enrolled was predominantly women (73.13%) and from these, 33.53% taking the monotherapy regimen, used angiotensin converting enzyme inhibitors (ACE-I). However, in combined therapy (66.47%) the most used drugs were the diuretics, especially in prescriptions associated to ACE-I. It was also observed that patients taking diuretics in monotherapy regimen showed significant effects in their serum lipid concentrations of lipids, in contrast with individuals taking combined therapy, which had no expressive alterations in their lipid profile. Theses results suggest that the antihypertensive therapy must be associated to a lipid monitoring process.
Acta medica portuguesa 21(6):567-74. · 0.09 Impact Factor