Helena Monteiro - Academia.edu (original) (raw)

Papers by Helena Monteiro

Research paper thumbnail of The renal effects of Bothrops jararacussu venom and the role of PLA2 and PAF blockers

Toxicon, Dec 1, 2001

The most common complication in the lethal cases of ophidian bites in Brazil is acute renal failu... more The most common complication in the lethal cases of ophidian bites in Brazil is acute renal failure, but its pathogenesis is obscure. The effects of Bothrops jararacussu venom (3, 10 and 30 microg/ml) were examined using the isolated perfused kidney from Wistar rats. Dexamethasone, and WEB 2086, a triazolobenzodiazepine substance, which is a platelet activating factor receptor antagonist, were tested for a possible blockade of the renal effects in the presence of 10 microg/ml of venom. The most intense effects of the venom were noticed at 120 min after using 30 microg/ml. We observed a decrease in the perfusion pressure and in the renal vascular resistance. However, the glomerular filtration rate (GFR) and the urinary flow (UF) increased significantly. The percent of sodium (%Na(tot)(+)) and potassium (%K(tot)(+)) tubular transport were also decreased. Dexamethasone was unable to block the effects of B. jararacussu in the kidney, while WEB 2086 blocked its effect in glomerular filtration rate, urinary flow and in the percentage of total tubular potassium reabsorption. We suggest that this venom promotes diuresis independently of perfusion pressure drop. The alterations in GFR, UF and %K(tot)(+) are probably mediated by platelet activating factor. Dexamethasone did not block the renal effects maybe because of the concentration used in this work or maybe the renal effects are promoted by the myotoxin, which does not have PLA(2) activity.

Research paper thumbnail of Anti-ophidian activity of Bredemeyera floribunda Willd. (Polygalaceae) root extract on the local effects induced by Bothrops jararacussu venom

Brazilian Journal of Medical and Biological Research, 2018

Bredemeyera floribunda roots are popularly used to treat snakebites in the semiarid region of Nor... more Bredemeyera floribunda roots are popularly used to treat snakebites in the semiarid region of Northeast Brazil, and previous studies indicate the anti-ophidian actions of triterpenoid saponins found in its roots. To assess B. floribunda root extract (BFRE) activity against the effects of Bothrops jararacussu venom (BjuV), antiphospholipasic, antiproteolytic, antihemorrhagic, antinecrotic, and anti-edematogenic activities were investigated in mice. Phytochemical analysis revealed the presence of saponins, flavonoids, and sugars, with rutin and saccharose being the major constituents of BFRE. Acute toxicity was determined and BFRE was nontoxic to mice. Phospholipase A2 and proteolytic activities induced by BjuV were inhibited in vitro by BFRE at all concentrations tested herein. BFRE (150 mg/kg) inhibited paw edema induced by BjuV (50 mg/animal), reducing total edema calculated by area under the curve, but carrageenan-induced paw edema was unchanged. Hemorrhagic and necrotizing actions of BjuV (50 mg/animal) were considerably decreased by BFRE treatment. Thus, BFRE blocked the toxic actions of B. jararacussu venom despite having no anti-inflammatory activity, which points to a direct inhibition of venom's toxins, as demonstrated in the in vitro assays. The larger amounts of rutin found in BFRE may play a role in this inhibition, since 3 0 ,4 0-OH flavonoids are known inhibitors of phospholipases A2.

Research paper thumbnail of Antimicrobial effect of Dinoponera quadriceps (Hymenoptera: Formicidae) venom against Staphylococcus aureus strains

Journal of Applied Microbiology, 2014

Aims: Dinoponera quadriceps venom (DqV) was examined to evaluate the antibacterial activity and i... more Aims: Dinoponera quadriceps venom (DqV) was examined to evaluate the antibacterial activity and its bactericidal action mechanism against Staphylococcus aureus. Methods and Results: DqV was tested against a standard strain of methicillinsensitive Staphylococcus aureus (MSSA), Staph. aureus ATCC 6538P and two standard strains of methicillin-resistant Staphylococcus aureus (MRSA), Staph. aureus ATCC 33591 and Staph. aureus CCBH 5330. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), the rate of kill and pH sensitivity of the DqV were determined by microdilution tests. Bactericidal and inhibitory concentrations of DqV were tested to check its action on Staph. aureus membrane permeability and cell morphology. The MIC and MBC of DqV were 6Á25 and 12Á5 lg ml À1 for Staph. aureus ATCC 6538P, 12Á5 and 50 lg ml À1 for Staph. aureus CCBH 5330 and 100 and 100 lg ml À1 for Staph. aureus ATCC 33591, respectively. Complete bacterial growth inhibition was observed after 4 h of incubation with the MBC of DqV. A lowest MIC was observed in alkaline pH. Alteration in membrane permeability was observed through the increase in crystal violet uptake, genetic material release and morphology in atomic force microscopy. Conclusions: The results suggest antibacterial activity of DqV against Staph. aureus and that the venom acts in the cell membrane. Significance and Impact of the Study: Alteration in membrane permeability may be associated with the antimicrobial activity of hymenopteran venoms.

Research paper thumbnail of Renal Effects Of The Lectin From Canavalia Brasiliensis Seeds

Protein & Peptide Letters, 2001

Page 1. 477 Protein and Peptide Letters, Vol. 8, No. 6, pp. 477-484, 2001 Bentham Science Publish... more Page 1. 477 Protein and Peptide Letters, Vol. 8, No. 6, pp. 477-484, 2001 Bentham Science Publishers Ltd. 0929-8665/01 $ 20.00 + .00 RENAL EFFECTS OF THE LECTIN FROM CANAVALIA BRASILIENSIS SEEDS Edson ...

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

Toxicon, 2006

Renal changes determined by Lys49 myotoxin I (BmTx I), isolated from Bothrops moojeni are well kn... more 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 mg/mL), a non-selective inhibitor of cyclooxygenase, and tezosentan (10 mg/mL), an endothelin antagonist. By means of the method of mesenteric vascular bed, it has been observed that B. moojeni myotoxin (5 mg/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.

Research paper thumbnail of Microcystin-LR promote intestinal secretion of water and electrolytes in rats

Toxicon, 2004

We showed previously that exposure to microcystin-LR causes renal toxic effects in isolated perfu... more We showed previously that exposure to microcystin-LR causes renal toxic effects in isolated perfused rat kidney, and that inflammatory mediators from supernatants of macrophages stimulated by microcystin-LR are involved in this process. The aim of this research was to examine water and electrolytes secretion in vivo, induced by microcystin-LR and supernatant of macrophages stimulated for this toxin (SUP.MphiS + MCLR), using perfused rat ileal segment and ligated intestinal loop models. We found microcystin-LR at 1 microg/ml (0.09 +/- 0.003* vs. control 0.07 +/- 0.001 g of secretion/2 cm of loop; P < 0.05*) and the SUP.MphiS + MCLR after 18 h postinoculation (0.10 +/- 0.003 vs. control 0.03 +/- 0.002 g/cm) caused intestinal secretion. In addition, microcystin-LR caused significant sodium secretion (-2.18 +/- 0.72* vs. control 2.18 +/- 0.50 microEq g(-1) min(-1)), potassium (-0.26 +/- 0.04* vs. control 0.32 +/- 0.03 microEq g(-1) min(-1)), chloride (MCLR = -3.29 +/- 1.93* vs. control 0.88 +/- 1.25 microEq g(-1) min(-1)) and water (-0.012 +/- 0.004* vs. control 0.002 +/- 0.002 ml g(-1) min(-1)). We also demonstrated SUP.MphiS + MCLR to induce intestinal secretion of electrolytes (sodium, potassium, chloride) and water. These findings suggested that microcystin-LR and lamina propria macrophages-derived mediators are able to induce intestinal secretion in vivo, probably via inhibition of protein phosphatase.

Research paper thumbnail of Effects of Thalassophryne nattereri fish venom in isolated perfused rat kidney

Toxicon, 2003

Thalassophryne nattereri, popularly known as Niquim, is a venomous fish responsible for many acci... more Thalassophryne nattereri, popularly known as Niquim, is a venomous fish responsible for many accidents in fishermen in the Northeast of Brazil. The effects of T. nattereri venom on renal physiology has not been tested. Isolated kidneys from Wistar rats of 240-280 g weight were perfused with Krebs-Henseleit solution containing 6 g% of previously dialyzed bovine serum albumin. The effects of Niquim venom were studied on the perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), percent of sodium tubular transport (%TNa þ), percent of potassium tubular transport (%TK þ) and percent of chloride tubular transport (%TCl-). The venom of T. nattereri (0.3, 1.0, and 3.0 mg/ml) was always added to the system 30 minutes after the beginning of each experiment ðn ¼ 6Þ: All experiments were preceded by 30 minutes internal control period and an external control group, where kidneys were perfused with only Krebs-Henseleit solution. All three doses tested promoted increases in PP and RVR. The first two doses also increased GFR and UF. The higher dose promoted decreases in GFR, UF, %TNa þ , %TK þ , %TCl 2. In the treated groups we observed hyalin casts inside all tubules and proteinaceous material in the urinary space. We conclude that the effects resulted from niquim venom agents that promoted a direct effect in kidney cells causing the release of vasoactive factors.

Research paper thumbnail of Action of anti-bothropic factor isolated from Didelphis marsupialis on renal effects of Bothrops erythromelas venom

Toxicon, 2005

Acute renal failure is the most common complication in the lethal cases caused by snakebites in B... more Acute renal failure is the most common complication in the lethal cases caused by snakebites in Brazil. Among the Brazilian venom snakes, Bothrops erythromelas is responsible for the majority of accidents in Northeastern Brazil. Didelphis marsupialis serum could inhibit myonecrotic, hemorrhagic, edematogenic hyperalgesic and lethal effects of envenomation determined by ophidian bites. In the present study, we evaluated the action of the anti-bothropic factor isolated from D. marsupialis on the renal effects promoted by B. erythromelas venom without systemic interference. Isolated kidneys from Wistar rats were perfused with Krebs-Henseleit solution containing 6% bovine serum albumin. We analyzed renal perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR), urinary flow (UF), and the percentages of sodium and potassium tubular transport (%TNa C , %TK C). The B. erythromelas venom (10 mg mL K1) decreased the PP (ctZ108.71G5.09 mmHg; BEZ65.21G5.6 mmHg*) and RVR (ctZ5.76G0.65 mmHg mL K1 g K1 min K1 ; BEZ3.10G0.45 mmHg mL K1 g K1 min K1 *). On the other hand, the GFR decreased at 60 min (ct 60 Z0.76G0.07 mL g K1 min K1 ; BE 60 Z0.42G0.12 mL g K1 min K1 *) and increased at 120 min (ct 120 Z0.72G0.01 mL g K1 min K1 ; BE 120 Z1.24G0.26 mL g K1 min K1 *). The UF increased significantly when compared with the control group (ctZ0.14G0.01 mL g K1 min K1 ; BEZ0.47G0.08 mL g K1 min K1 *). The venom reduced the %TNa C (ct 90 Z79.18G0.88%; BE 90 Z58.35G4.86%*) and %TK C (ct 90 Z67.20G4.04%; BE 90 Z57.32G5.26%*) The antibothropic factor from D. marsupialis (10 mg mL K1) incubated with B. erythromelas venom (10 mg mL K1) blocked the effects on PP,

Research paper thumbnail of Renal effects of supernatant from rat peritoneal macrophages activated by microcystin-LR: role protein mediators

Toxicon, 2003

We have demonstrated previously that microcystin-LR promoted some renal alterations using the iso... more We have demonstrated previously that microcystin-LR promoted some renal alterations using the isolated perfused rat kidney preparation. However, these effects were not proved to be direct or indirect. The aim of the current work is to examine the renal effects promoted by supernatants from rat macrophages stimulated with microcystin-LR and the role of inflammatory mediators. Peritoneal macrophages were collected previously and were incubated for 1 h in fresh medium (control) and in medium containing microcystin-LR. Dexamethasone, quinacrine, thalidomide and cycloheximide were administered 30 min before microcystin-LR. Supernatants of macrophages stimulated with or without pharmacological inhibitors were added on the perfused rat kidney model. The infusion of macrophages supernatants stimulated by microcystin-LR caused significant increases in renal vascular resistance (C: 4.93^0.33 vs T: 5.15^0.21), glomerular filtration rate (C: 0.559^0.008 vs T: 0.978^0.15) and urinary flow (C: 0.16^0.01 vs T: 0.23^0.03). Cycloheximide, quinacrine and dexamethasone blocked these effects and thalidomide blocked renal vascular resistance. Macrophages stimulated by microcystin-LR release mediators capable of promoting nephotoxicity in isolated perfused rat kidney. Phospholipase A 2 , TNF-a and other protein mediators appear to be involved on its renal toxic mechanism.

Research paper thumbnail of Renal toxicity of Bothrops moojeni snake venom and its main myotoxins

Toxicon, 2002

Acute renal failure is one the most common systemic complications after snakebite, however, its p... more Acute renal failure is one the most common systemic complications after snakebite, however, its pathogenesis remains obscure. In this study we evaluated the renal effects of Bothrops moojeni venom and its myotoxins (Bmtx-I and BmtxII) in rat isolated perfused kidneys. The myotoxins were purified by ion-exchange chromatography and reverse phase HPLC. The whole venom (10 microg/ml) and myotoxins (5 microg/ml) were added to the perfusion system 30 min after the beginning of each perfusion. The renal effects were compared to a control group perfused with modified Krebs-Henseleit solution alone. B. moojeni venom decreased the perfusion pressure (PP), renal vascular resistance (RVR), and the percent sodium, potassium and chloride tubular transport (%TNa(+), %TK(+), %TCl(-)). In contrast, the venom increased the urinary flow (UF), glomerular filtration rate (GFR), and the sodium, potassium and chloride excretion (ENa(+), EK(+), ECl(-)). The renal effects of myotoxin I was very similar to those of the whole venom, but there was an increase rather than a decrease in the PP and RVR. Myotoxin II had no effect on renal physiology, except for a transient decrease in %TK(+). In conclusion, B. moojeni venom caused intense alterations in renal physiology, including a drop in vascular resistance associated with diuresis, natriuresis and kaliuresis. Bmtx-I had an opposite effect when compared to whole venom, showed in the parameters of PP and RVR. Bmtx-II had a mild effect in %TK(+). The apparent inability of Bmtx-II to induce the renal effect similarly to Bmtx-I should be explained by the absence in the Bmtx-II of the C-terminal lysine rich region.

Research paper thumbnail of Renal Alterations Promoted By The Lectins From Canavalia Ensiformis (Cona) And Dioclea Guianensis (Dguil) Seeds

Protein & Peptide Letters, 2003

The lectin from the seeds of Canavalia ensiformis (ConA) and Dioclea guianensis (DguiL) was teste... more The lectin from the seeds of Canavalia ensiformis (ConA) and Dioclea guianensis (DguiL) was tested upon its renal effects using the isolated perfusion rat kidney method. Both lectins (10 microg/ml) affected perfusion pressure and renal vascular resistance, but DguiL showed a much greater action than ConA. However, ConA, but not DguiL, affected potassium tubular transport.

Research paper thumbnail of Renal effects induced by the lectin from Vatairea macrocarpa seeds

Journal of Pharmacy and Pharmacology, 2005

Lectins are glycoproteins that interact reversibly and specifically with carbohydrates. The renal... more Lectins are glycoproteins that interact reversibly and specifically with carbohydrates. The renal effects of the galactose-binding lectin from the seeds of Vatairea macrocarpa were investigated. Isolated kidneys from Wistar rats (240–280 g) were perfused with Krebs-Henseleit solution containing 6% bovine serum albumin. The V. macrocarpa lectin (10 μg mL−1) increased the perfusion pressure, renal vascular resistance, urinary flow and glomerular filtration rate. However, V. macrocarpa lectin did not change the percentage sodium, potassium or chloride tubular transport. Pretreatment with lectin-galactose complex significantly blocked the increase in perfusion pressure, renal vascular resistance, urinary flow and glomerular filtration rate. The control group showed a small amount of a proteinaceous material in the urinary space, although no alteration in the renal tubules was detected. The administration of galactose alone did not modify the functional parameters of the kidney. Kidneys ...

Research paper thumbnail of Renal and cardiovascular effects of Bothrops marajoensis venom and phospholipase A2

Toxicon, 2010

Bothrops marajoensis is found in the savannah of Marajó Island in the State of Pará and regions o... more Bothrops marajoensis is found in the savannah of Marajó Island in the State of Pará and regions of Amapá State, Brazil. The aim of the work was to study the renal and cardiovascular effects of the B. marajoensis venom and phospholipase A(2) (PLA(2)). The venom was fractionated by Protein Pack 5PW. N-terminal amino acid sequencing of sPLA(2) showed amino acid identity with other lysine K49 sPLA(2)s of snake venom. B. marajoensis venom (30 microg/mL) decreased the perfusion pressure, renal vascular resistance, urinary flow, glomerular filtration rate and sodium tubular transport. PLA(2) did not change the renal parameters. The perfusion pressure of the mesenteric bed did not change after infusion of venom. In isolated heart, the venom decreased the force of contraction and increased PP but did not change coronary flow. In the arterial pressure, the venom and PLA(2) decreased mean arterial pressure and cardiac frequency. The presence of atrial flutter and late hyperpolarisation reversed, indicating QRS complex arrhythmia and dysfunction in atrial conduction. In conclusion, B. marajoensis venom and PLA(2) induce hypotension and bradycardia while simultaneously blocking electrical conduction in the heart. Moreover, the decrease in glomerular filtration rate, urinary flow and electrolyte transport demonstrates physiological changes to the renal system.

Research paper thumbnail of Gingerol Fraction from Zingiber officinale Protects against Gentamicin-Induced Nephrotoxicity

Antimicrobial Agents and Chemotherapy, 2014

ABSTRACTNephrotoxicity is the main complication of gentamicin (GM) treatment. GM induces renal da... more ABSTRACTNephrotoxicity is the main complication of gentamicin (GM) treatment. GM induces renal damage by overproduction of reactive oxygen species and inflammation in proximal tubular cells. Phenolic compounds from ginger, called gingerols, have been demonstrated to have antioxidant and anti-inflammatory effects. We investigated if oral treatment with an enriched solution of gingerols (GF) would promote a nephroprotective effect in an animal nephropathy model. The following six groups of male Wistar rats were studied: (i) control group (CT group); (ii) gingerol solution control group (GF group); (iii) gentamicin treatment group (GM group), receiving 100 mg/kg of body weight intraperitoneally (i.p.); and (iv to vi) gentamicin groups also receiving GF, at doses of 6.25, 12.5, and 25 mg/kg, respectively (GM+GF groups). Animals from the GM group had a significant decrease in creatinine clearance and higher levels of urinary protein excretion. This was associated with markers of oxidativ...

Research paper thumbnail of Renal and antibacterial effects induced by myotoxin I and II isolated from Bothrops jararacussu venom

Toxicon, 2005

Bothrops jararacussu myotoxin I (BthTx-I; Lys 49) and II (BthTX-II; Asp 49) were purified by ion-... more Bothrops jararacussu myotoxin I (BthTx-I; Lys 49) and II (BthTX-II; Asp 49) were purified by ion-exchange chromatography and reverse phase HPLC. In this work we used the isolated perfused rat kidney method to evaluate the renal effects of B. jararacussu myotoxins I (Lys49 PLA 2) and II (Asp49 PLA 2) and their possible blockage by indomethacin. BthTX-I (5 mg/ml) and BthTX-II (5 mg/ml) increased perfusion pressure (PP; ct 120 Z110.28G3.70 mmHg; BthTX IZ171.28G 6.30* mmHg; BthTX IIZ175.50G7.20* mmHg), renal vascular resistance (RVR; ct 120 Z5.49 G0.54 mmHg/ml.g K1 min K1 ; BthTX IZ8.62G0.37* mmHg/ml g K1 min K1 ; BthTX IIZ8.9G0.36* mmHg/ml g K1 min K1), urinary flow (UF; ct 120 Z 0.14G0.01 ml g K1 min K1 ; BthTX IZ0.32G0.05* ml g K1 min K1 ; BthTX IIZ0.37G0.01* ml g K1 min K1) and glomerular filtration rate (GFR; ct 120 Z0.72G0.10 ml g K1 min K1 ; BthTX IZ0.85G0.13* ml g K1 min K1 ; BthTX IIZ1.22G 0.28* ml g K1 min K1). In contrast decreased the percent of sodium tubular transport (%TNa C ; ct 120 Z79,76G0.56; BthTX IZ62.23G4.12*; BthTX IIZ70.96G2.93*) and percent of potassium tubular transport (%TK C ;ct 120 Z66.80G3.69; BthTX IZ55.76G5.57*; BthTX IIZ50.86G6.16*). Indomethacin antagonized the vascular, glomerular and tubular effects promoted by BthTX I and it's partially blocked the effects of BthTX II. In this work also evaluated the antibacterial effects of BthTx-I and BthTx-II against Xanthomonas axonopodis. pv. passiflorae (Gram-negative bacteria) and we observed that both PLA2 showed antibacterial activity. Also we observed that proteins Also we observed that proteins chemically modified with 4bromophenacyl bromide (r-BPB) decrease significantly the antibacterial effect of both PLA 2. In conclusion, BthTx I and BthTX II caused renal alteration and presented activity antimicrobial. The indomethacin was able to antagonize totally the renal effects induced by BthTx I and partially the effects promoted by BthTx II, suggesting involvement of inflammatory mediators in

Research paper thumbnail of High Salt Intake Promotes Different Responses to Urodilatin and Uroguanylin in the Isolated Rat Kidney

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, Jan 12, 2017

Urodilatin (UD) and uroguanylin (UGN) have been implicated in the regulation of salt and water ho... more Urodilatin (UD) and uroguanylin (UGN) have been implicated in the regulation of salt and water homeostasis, particularly in the balance handling of salt intake. In this sense, the aim of the present work was to study the main effects of these peptides in kidneys from animals subjected to high NaCl (2%) intake, during 10 days in metabolic cages. The control group received only normal water, whereas the treated group drank 2% solution of NaCl (NaCl 2%). In addition, we studied effect of subthreshold UD (0.14 nM) and UGN (0.06 μM) doses in NaCl 2% after a 30-min control period. Kidney perfusion was performed with Krebs-Henseleit containing 6 g% bovine albumin previously dialyzed. The effects of UD (0.14 nM) promoted reduction of PP, RVR, and UF in the NaCl 2% group. We also observed an increase in %TNa+ and %TCl-. The main effects of UGN in NaCl 2% were increase in PP, UF, and GFR, followed by a reduction in %TNa+ and %TCl-. After an increased intake of salt, physiological pathways are...

Research paper thumbnail of Pulmonary mechanic and lung histology induced by Crotalus durissus cascavella snake venom

Toxicon : official journal of the International Society on Toxinology, 2017

This study have analyzed the pulmonary function in an experimental model of acute lung injury, in... more This study have analyzed the pulmonary function in an experimental model of acute lung injury, induced by the Crotalus durissus cascavella venom (C. d. cascavella) (3.0 μg/kg - i.p), in pulmonary mechanic and histology at 1 h, 3 h, 6 h, 12 h and 24 h after inoculation. The C. d. cascavella venom led to an increase in Newtonian Resistance (RN), Tissue Resistance (G) and Tissue Elastance (H) in all groups when compared to the control, particularly at 12 h and 24 h. The Histeresivity (η) increased 6 h, 12 h and 24 h after inoculation. There was a decrease in Static Compliance (CST) at 6 h, 12 h and 24 h and inspiratory capacity (IC) at 3 h, 6 h, 12 h and 24 h. C. d. cascavella venom showed significant morphological changes such as atelectasis, emphysema, hemorrhage, polymorphonuclear inflammatory infiltrate, edema and congestion. After a challenge with methacholine (MCh), RN demonstrated significant changes at 6, 12 and 24 h. This venom caused mechanical and histopathological changes i...

Research paper thumbnail of Renal effects of Bunodosoma caissarum crude extract: Prostaglandin and endothelin involvement

Toxicon : official journal of the International Society on Toxinology, Jan 23, 2017

Sea anemones contain a variety of interesting biologically active compounds, including some poten... more Sea anemones contain a variety of interesting biologically active compounds, including some potent toxins. PLA2 from Bunodosoma caissarum, a sea anemone endemic in the Brazilian southern coast, has shown renal alterations on isolated kidney. The aim of this study was to evaluate the renal and vascular effects of B. caissarum crude extract (BcE) on isolated perfused kidney and arteriolar mesenteric bed, as well the involvement of prostaglandins and endothelin. BcE did not show any effect on arteriolar mesenteric bed, but increased perfusion pressure, renal vascular resistance, urinary flow, glomerular filtration rate and decreased the percentage of sodium tubular transport on isolated perfused kidney. Indomethacin blocked the renal effects induced by BcE and tezosentan only partially blocked these effects. These results demonstrate the effects of BcE on kidney in situ, suggesting the involvement of prostaglandins and endothelin.

Research paper thumbnail of Differences between renal effects of venom from two Bothrops jararaca populations from southeastern and southern Brazil

Toxicon, 2016

Components from animal venoms may vary according to the snake&amp... more Components from animal venoms may vary according to the snake's age, gender and region of origin. Recently, we performed a proteomic analysis of Bothrops jararaca venom from southern (BjSv) and southeastern (BjSEv) Brazil, showing differences in the venom composition, as well as its biological activity. To continue the study, we report in this short communication the different effects induced by the BjSEv and BjSv on isolated kidney and MDCK renal cells. BjSEv decreased perfusion pressure (PP) and renal vascular resistance (RVR) and increased urinary flow (UF) and glomerular filtration rate (GFR), while BjSv did not alter PP and RVR and reduced UF and GFR. Both types of venom, more expressively BjSEv, reduced %TNa(+), %TK(+) and %Cl(-). In MDCK cells, the two types of venom showed cytotoxicity with IC50 of 1.22 μg/mL for BjSv and 1.18 μg/mL for BjSEv and caused different profiles of cell death, with BjSv being more necrotic. In conclusion, we suggest that BjSv is more nephrotoxic than BjSEv.

Research paper thumbnail of Toxins Polypeptide That Interfere with the Flow of Calcium (Channels and Receptors Intra and Extra-Cellular)

Sciprints, 2016

The voltage-dependent calcium channels (Cav) are a family of multigene channel that plays an esse... more The voltage-dependent calcium channels (Cav) are a family of multigene channel that plays an essential role in regulating a variety of cellular functions. These channels are categorized as type L-, N-, P / Q-, R- or T, based on their electrophysiological and pharmacological properties. Activation of these channels and Ca2 + entry is required in many physiological processes such as muscle contraction and release of hormones and neurotransmitters, and many others, for example in the contraction mechanism, and vascular relaxation.

Research paper thumbnail of The renal effects of Bothrops jararacussu venom and the role of PLA2 and PAF blockers

Toxicon, Dec 1, 2001

The most common complication in the lethal cases of ophidian bites in Brazil is acute renal failu... more The most common complication in the lethal cases of ophidian bites in Brazil is acute renal failure, but its pathogenesis is obscure. The effects of Bothrops jararacussu venom (3, 10 and 30 microg/ml) were examined using the isolated perfused kidney from Wistar rats. Dexamethasone, and WEB 2086, a triazolobenzodiazepine substance, which is a platelet activating factor receptor antagonist, were tested for a possible blockade of the renal effects in the presence of 10 microg/ml of venom. The most intense effects of the venom were noticed at 120 min after using 30 microg/ml. We observed a decrease in the perfusion pressure and in the renal vascular resistance. However, the glomerular filtration rate (GFR) and the urinary flow (UF) increased significantly. The percent of sodium (%Na(tot)(+)) and potassium (%K(tot)(+)) tubular transport were also decreased. Dexamethasone was unable to block the effects of B. jararacussu in the kidney, while WEB 2086 blocked its effect in glomerular filtration rate, urinary flow and in the percentage of total tubular potassium reabsorption. We suggest that this venom promotes diuresis independently of perfusion pressure drop. The alterations in GFR, UF and %K(tot)(+) are probably mediated by platelet activating factor. Dexamethasone did not block the renal effects maybe because of the concentration used in this work or maybe the renal effects are promoted by the myotoxin, which does not have PLA(2) activity.

Research paper thumbnail of Anti-ophidian activity of Bredemeyera floribunda Willd. (Polygalaceae) root extract on the local effects induced by Bothrops jararacussu venom

Brazilian Journal of Medical and Biological Research, 2018

Bredemeyera floribunda roots are popularly used to treat snakebites in the semiarid region of Nor... more Bredemeyera floribunda roots are popularly used to treat snakebites in the semiarid region of Northeast Brazil, and previous studies indicate the anti-ophidian actions of triterpenoid saponins found in its roots. To assess B. floribunda root extract (BFRE) activity against the effects of Bothrops jararacussu venom (BjuV), antiphospholipasic, antiproteolytic, antihemorrhagic, antinecrotic, and anti-edematogenic activities were investigated in mice. Phytochemical analysis revealed the presence of saponins, flavonoids, and sugars, with rutin and saccharose being the major constituents of BFRE. Acute toxicity was determined and BFRE was nontoxic to mice. Phospholipase A2 and proteolytic activities induced by BjuV were inhibited in vitro by BFRE at all concentrations tested herein. BFRE (150 mg/kg) inhibited paw edema induced by BjuV (50 mg/animal), reducing total edema calculated by area under the curve, but carrageenan-induced paw edema was unchanged. Hemorrhagic and necrotizing actions of BjuV (50 mg/animal) were considerably decreased by BFRE treatment. Thus, BFRE blocked the toxic actions of B. jararacussu venom despite having no anti-inflammatory activity, which points to a direct inhibition of venom's toxins, as demonstrated in the in vitro assays. The larger amounts of rutin found in BFRE may play a role in this inhibition, since 3 0 ,4 0-OH flavonoids are known inhibitors of phospholipases A2.

Research paper thumbnail of Antimicrobial effect of Dinoponera quadriceps (Hymenoptera: Formicidae) venom against Staphylococcus aureus strains

Journal of Applied Microbiology, 2014

Aims: Dinoponera quadriceps venom (DqV) was examined to evaluate the antibacterial activity and i... more Aims: Dinoponera quadriceps venom (DqV) was examined to evaluate the antibacterial activity and its bactericidal action mechanism against Staphylococcus aureus. Methods and Results: DqV was tested against a standard strain of methicillinsensitive Staphylococcus aureus (MSSA), Staph. aureus ATCC 6538P and two standard strains of methicillin-resistant Staphylococcus aureus (MRSA), Staph. aureus ATCC 33591 and Staph. aureus CCBH 5330. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), the rate of kill and pH sensitivity of the DqV were determined by microdilution tests. Bactericidal and inhibitory concentrations of DqV were tested to check its action on Staph. aureus membrane permeability and cell morphology. The MIC and MBC of DqV were 6Á25 and 12Á5 lg ml À1 for Staph. aureus ATCC 6538P, 12Á5 and 50 lg ml À1 for Staph. aureus CCBH 5330 and 100 and 100 lg ml À1 for Staph. aureus ATCC 33591, respectively. Complete bacterial growth inhibition was observed after 4 h of incubation with the MBC of DqV. A lowest MIC was observed in alkaline pH. Alteration in membrane permeability was observed through the increase in crystal violet uptake, genetic material release and morphology in atomic force microscopy. Conclusions: The results suggest antibacterial activity of DqV against Staph. aureus and that the venom acts in the cell membrane. Significance and Impact of the Study: Alteration in membrane permeability may be associated with the antimicrobial activity of hymenopteran venoms.

Research paper thumbnail of Renal Effects Of The Lectin From Canavalia Brasiliensis Seeds

Protein & Peptide Letters, 2001

Page 1. 477 Protein and Peptide Letters, Vol. 8, No. 6, pp. 477-484, 2001 Bentham Science Publish... more Page 1. 477 Protein and Peptide Letters, Vol. 8, No. 6, pp. 477-484, 2001 Bentham Science Publishers Ltd. 0929-8665/01 $ 20.00 + .00 RENAL EFFECTS OF THE LECTIN FROM CANAVALIA BRASILIENSIS SEEDS Edson ...

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

Toxicon, 2006

Renal changes determined by Lys49 myotoxin I (BmTx I), isolated from Bothrops moojeni are well kn... more 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 mg/mL), a non-selective inhibitor of cyclooxygenase, and tezosentan (10 mg/mL), an endothelin antagonist. By means of the method of mesenteric vascular bed, it has been observed that B. moojeni myotoxin (5 mg/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.

Research paper thumbnail of Microcystin-LR promote intestinal secretion of water and electrolytes in rats

Toxicon, 2004

We showed previously that exposure to microcystin-LR causes renal toxic effects in isolated perfu... more We showed previously that exposure to microcystin-LR causes renal toxic effects in isolated perfused rat kidney, and that inflammatory mediators from supernatants of macrophages stimulated by microcystin-LR are involved in this process. The aim of this research was to examine water and electrolytes secretion in vivo, induced by microcystin-LR and supernatant of macrophages stimulated for this toxin (SUP.MphiS + MCLR), using perfused rat ileal segment and ligated intestinal loop models. We found microcystin-LR at 1 microg/ml (0.09 +/- 0.003* vs. control 0.07 +/- 0.001 g of secretion/2 cm of loop; P < 0.05*) and the SUP.MphiS + MCLR after 18 h postinoculation (0.10 +/- 0.003 vs. control 0.03 +/- 0.002 g/cm) caused intestinal secretion. In addition, microcystin-LR caused significant sodium secretion (-2.18 +/- 0.72* vs. control 2.18 +/- 0.50 microEq g(-1) min(-1)), potassium (-0.26 +/- 0.04* vs. control 0.32 +/- 0.03 microEq g(-1) min(-1)), chloride (MCLR = -3.29 +/- 1.93* vs. control 0.88 +/- 1.25 microEq g(-1) min(-1)) and water (-0.012 +/- 0.004* vs. control 0.002 +/- 0.002 ml g(-1) min(-1)). We also demonstrated SUP.MphiS + MCLR to induce intestinal secretion of electrolytes (sodium, potassium, chloride) and water. These findings suggested that microcystin-LR and lamina propria macrophages-derived mediators are able to induce intestinal secretion in vivo, probably via inhibition of protein phosphatase.

Research paper thumbnail of Effects of Thalassophryne nattereri fish venom in isolated perfused rat kidney

Toxicon, 2003

Thalassophryne nattereri, popularly known as Niquim, is a venomous fish responsible for many acci... more Thalassophryne nattereri, popularly known as Niquim, is a venomous fish responsible for many accidents in fishermen in the Northeast of Brazil. The effects of T. nattereri venom on renal physiology has not been tested. Isolated kidneys from Wistar rats of 240-280 g weight were perfused with Krebs-Henseleit solution containing 6 g% of previously dialyzed bovine serum albumin. The effects of Niquim venom were studied on the perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), percent of sodium tubular transport (%TNa þ), percent of potassium tubular transport (%TK þ) and percent of chloride tubular transport (%TCl-). The venom of T. nattereri (0.3, 1.0, and 3.0 mg/ml) was always added to the system 30 minutes after the beginning of each experiment ðn ¼ 6Þ: All experiments were preceded by 30 minutes internal control period and an external control group, where kidneys were perfused with only Krebs-Henseleit solution. All three doses tested promoted increases in PP and RVR. The first two doses also increased GFR and UF. The higher dose promoted decreases in GFR, UF, %TNa þ , %TK þ , %TCl 2. In the treated groups we observed hyalin casts inside all tubules and proteinaceous material in the urinary space. We conclude that the effects resulted from niquim venom agents that promoted a direct effect in kidney cells causing the release of vasoactive factors.

Research paper thumbnail of Action of anti-bothropic factor isolated from Didelphis marsupialis on renal effects of Bothrops erythromelas venom

Toxicon, 2005

Acute renal failure is the most common complication in the lethal cases caused by snakebites in B... more Acute renal failure is the most common complication in the lethal cases caused by snakebites in Brazil. Among the Brazilian venom snakes, Bothrops erythromelas is responsible for the majority of accidents in Northeastern Brazil. Didelphis marsupialis serum could inhibit myonecrotic, hemorrhagic, edematogenic hyperalgesic and lethal effects of envenomation determined by ophidian bites. In the present study, we evaluated the action of the anti-bothropic factor isolated from D. marsupialis on the renal effects promoted by B. erythromelas venom without systemic interference. Isolated kidneys from Wistar rats were perfused with Krebs-Henseleit solution containing 6% bovine serum albumin. We analyzed renal perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR), urinary flow (UF), and the percentages of sodium and potassium tubular transport (%TNa C , %TK C). The B. erythromelas venom (10 mg mL K1) decreased the PP (ctZ108.71G5.09 mmHg; BEZ65.21G5.6 mmHg*) and RVR (ctZ5.76G0.65 mmHg mL K1 g K1 min K1 ; BEZ3.10G0.45 mmHg mL K1 g K1 min K1 *). On the other hand, the GFR decreased at 60 min (ct 60 Z0.76G0.07 mL g K1 min K1 ; BE 60 Z0.42G0.12 mL g K1 min K1 *) and increased at 120 min (ct 120 Z0.72G0.01 mL g K1 min K1 ; BE 120 Z1.24G0.26 mL g K1 min K1 *). The UF increased significantly when compared with the control group (ctZ0.14G0.01 mL g K1 min K1 ; BEZ0.47G0.08 mL g K1 min K1 *). The venom reduced the %TNa C (ct 90 Z79.18G0.88%; BE 90 Z58.35G4.86%*) and %TK C (ct 90 Z67.20G4.04%; BE 90 Z57.32G5.26%*) The antibothropic factor from D. marsupialis (10 mg mL K1) incubated with B. erythromelas venom (10 mg mL K1) blocked the effects on PP,

Research paper thumbnail of Renal effects of supernatant from rat peritoneal macrophages activated by microcystin-LR: role protein mediators

Toxicon, 2003

We have demonstrated previously that microcystin-LR promoted some renal alterations using the iso... more We have demonstrated previously that microcystin-LR promoted some renal alterations using the isolated perfused rat kidney preparation. However, these effects were not proved to be direct or indirect. The aim of the current work is to examine the renal effects promoted by supernatants from rat macrophages stimulated with microcystin-LR and the role of inflammatory mediators. Peritoneal macrophages were collected previously and were incubated for 1 h in fresh medium (control) and in medium containing microcystin-LR. Dexamethasone, quinacrine, thalidomide and cycloheximide were administered 30 min before microcystin-LR. Supernatants of macrophages stimulated with or without pharmacological inhibitors were added on the perfused rat kidney model. The infusion of macrophages supernatants stimulated by microcystin-LR caused significant increases in renal vascular resistance (C: 4.93^0.33 vs T: 5.15^0.21), glomerular filtration rate (C: 0.559^0.008 vs T: 0.978^0.15) and urinary flow (C: 0.16^0.01 vs T: 0.23^0.03). Cycloheximide, quinacrine and dexamethasone blocked these effects and thalidomide blocked renal vascular resistance. Macrophages stimulated by microcystin-LR release mediators capable of promoting nephotoxicity in isolated perfused rat kidney. Phospholipase A 2 , TNF-a and other protein mediators appear to be involved on its renal toxic mechanism.

Research paper thumbnail of Renal toxicity of Bothrops moojeni snake venom and its main myotoxins

Toxicon, 2002

Acute renal failure is one the most common systemic complications after snakebite, however, its p... more Acute renal failure is one the most common systemic complications after snakebite, however, its pathogenesis remains obscure. In this study we evaluated the renal effects of Bothrops moojeni venom and its myotoxins (Bmtx-I and BmtxII) in rat isolated perfused kidneys. The myotoxins were purified by ion-exchange chromatography and reverse phase HPLC. The whole venom (10 microg/ml) and myotoxins (5 microg/ml) were added to the perfusion system 30 min after the beginning of each perfusion. The renal effects were compared to a control group perfused with modified Krebs-Henseleit solution alone. B. moojeni venom decreased the perfusion pressure (PP), renal vascular resistance (RVR), and the percent sodium, potassium and chloride tubular transport (%TNa(+), %TK(+), %TCl(-)). In contrast, the venom increased the urinary flow (UF), glomerular filtration rate (GFR), and the sodium, potassium and chloride excretion (ENa(+), EK(+), ECl(-)). The renal effects of myotoxin I was very similar to those of the whole venom, but there was an increase rather than a decrease in the PP and RVR. Myotoxin II had no effect on renal physiology, except for a transient decrease in %TK(+). In conclusion, B. moojeni venom caused intense alterations in renal physiology, including a drop in vascular resistance associated with diuresis, natriuresis and kaliuresis. Bmtx-I had an opposite effect when compared to whole venom, showed in the parameters of PP and RVR. Bmtx-II had a mild effect in %TK(+). The apparent inability of Bmtx-II to induce the renal effect similarly to Bmtx-I should be explained by the absence in the Bmtx-II of the C-terminal lysine rich region.

Research paper thumbnail of Renal Alterations Promoted By The Lectins From Canavalia Ensiformis (Cona) And Dioclea Guianensis (Dguil) Seeds

Protein & Peptide Letters, 2003

The lectin from the seeds of Canavalia ensiformis (ConA) and Dioclea guianensis (DguiL) was teste... more The lectin from the seeds of Canavalia ensiformis (ConA) and Dioclea guianensis (DguiL) was tested upon its renal effects using the isolated perfusion rat kidney method. Both lectins (10 microg/ml) affected perfusion pressure and renal vascular resistance, but DguiL showed a much greater action than ConA. However, ConA, but not DguiL, affected potassium tubular transport.

Research paper thumbnail of Renal effects induced by the lectin from Vatairea macrocarpa seeds

Journal of Pharmacy and Pharmacology, 2005

Lectins are glycoproteins that interact reversibly and specifically with carbohydrates. The renal... more Lectins are glycoproteins that interact reversibly and specifically with carbohydrates. The renal effects of the galactose-binding lectin from the seeds of Vatairea macrocarpa were investigated. Isolated kidneys from Wistar rats (240–280 g) were perfused with Krebs-Henseleit solution containing 6% bovine serum albumin. The V. macrocarpa lectin (10 μg mL−1) increased the perfusion pressure, renal vascular resistance, urinary flow and glomerular filtration rate. However, V. macrocarpa lectin did not change the percentage sodium, potassium or chloride tubular transport. Pretreatment with lectin-galactose complex significantly blocked the increase in perfusion pressure, renal vascular resistance, urinary flow and glomerular filtration rate. The control group showed a small amount of a proteinaceous material in the urinary space, although no alteration in the renal tubules was detected. The administration of galactose alone did not modify the functional parameters of the kidney. Kidneys ...

Research paper thumbnail of Renal and cardiovascular effects of Bothrops marajoensis venom and phospholipase A2

Toxicon, 2010

Bothrops marajoensis is found in the savannah of Marajó Island in the State of Pará and regions o... more Bothrops marajoensis is found in the savannah of Marajó Island in the State of Pará and regions of Amapá State, Brazil. The aim of the work was to study the renal and cardiovascular effects of the B. marajoensis venom and phospholipase A(2) (PLA(2)). The venom was fractionated by Protein Pack 5PW. N-terminal amino acid sequencing of sPLA(2) showed amino acid identity with other lysine K49 sPLA(2)s of snake venom. B. marajoensis venom (30 microg/mL) decreased the perfusion pressure, renal vascular resistance, urinary flow, glomerular filtration rate and sodium tubular transport. PLA(2) did not change the renal parameters. The perfusion pressure of the mesenteric bed did not change after infusion of venom. In isolated heart, the venom decreased the force of contraction and increased PP but did not change coronary flow. In the arterial pressure, the venom and PLA(2) decreased mean arterial pressure and cardiac frequency. The presence of atrial flutter and late hyperpolarisation reversed, indicating QRS complex arrhythmia and dysfunction in atrial conduction. In conclusion, B. marajoensis venom and PLA(2) induce hypotension and bradycardia while simultaneously blocking electrical conduction in the heart. Moreover, the decrease in glomerular filtration rate, urinary flow and electrolyte transport demonstrates physiological changes to the renal system.

Research paper thumbnail of Gingerol Fraction from Zingiber officinale Protects against Gentamicin-Induced Nephrotoxicity

Antimicrobial Agents and Chemotherapy, 2014

ABSTRACTNephrotoxicity is the main complication of gentamicin (GM) treatment. GM induces renal da... more ABSTRACTNephrotoxicity is the main complication of gentamicin (GM) treatment. GM induces renal damage by overproduction of reactive oxygen species and inflammation in proximal tubular cells. Phenolic compounds from ginger, called gingerols, have been demonstrated to have antioxidant and anti-inflammatory effects. We investigated if oral treatment with an enriched solution of gingerols (GF) would promote a nephroprotective effect in an animal nephropathy model. The following six groups of male Wistar rats were studied: (i) control group (CT group); (ii) gingerol solution control group (GF group); (iii) gentamicin treatment group (GM group), receiving 100 mg/kg of body weight intraperitoneally (i.p.); and (iv to vi) gentamicin groups also receiving GF, at doses of 6.25, 12.5, and 25 mg/kg, respectively (GM+GF groups). Animals from the GM group had a significant decrease in creatinine clearance and higher levels of urinary protein excretion. This was associated with markers of oxidativ...

Research paper thumbnail of Renal and antibacterial effects induced by myotoxin I and II isolated from Bothrops jararacussu venom

Toxicon, 2005

Bothrops jararacussu myotoxin I (BthTx-I; Lys 49) and II (BthTX-II; Asp 49) were purified by ion-... more Bothrops jararacussu myotoxin I (BthTx-I; Lys 49) and II (BthTX-II; Asp 49) were purified by ion-exchange chromatography and reverse phase HPLC. In this work we used the isolated perfused rat kidney method to evaluate the renal effects of B. jararacussu myotoxins I (Lys49 PLA 2) and II (Asp49 PLA 2) and their possible blockage by indomethacin. BthTX-I (5 mg/ml) and BthTX-II (5 mg/ml) increased perfusion pressure (PP; ct 120 Z110.28G3.70 mmHg; BthTX IZ171.28G 6.30* mmHg; BthTX IIZ175.50G7.20* mmHg), renal vascular resistance (RVR; ct 120 Z5.49 G0.54 mmHg/ml.g K1 min K1 ; BthTX IZ8.62G0.37* mmHg/ml g K1 min K1 ; BthTX IIZ8.9G0.36* mmHg/ml g K1 min K1), urinary flow (UF; ct 120 Z 0.14G0.01 ml g K1 min K1 ; BthTX IZ0.32G0.05* ml g K1 min K1 ; BthTX IIZ0.37G0.01* ml g K1 min K1) and glomerular filtration rate (GFR; ct 120 Z0.72G0.10 ml g K1 min K1 ; BthTX IZ0.85G0.13* ml g K1 min K1 ; BthTX IIZ1.22G 0.28* ml g K1 min K1). In contrast decreased the percent of sodium tubular transport (%TNa C ; ct 120 Z79,76G0.56; BthTX IZ62.23G4.12*; BthTX IIZ70.96G2.93*) and percent of potassium tubular transport (%TK C ;ct 120 Z66.80G3.69; BthTX IZ55.76G5.57*; BthTX IIZ50.86G6.16*). Indomethacin antagonized the vascular, glomerular and tubular effects promoted by BthTX I and it's partially blocked the effects of BthTX II. In this work also evaluated the antibacterial effects of BthTx-I and BthTx-II against Xanthomonas axonopodis. pv. passiflorae (Gram-negative bacteria) and we observed that both PLA2 showed antibacterial activity. Also we observed that proteins Also we observed that proteins chemically modified with 4bromophenacyl bromide (r-BPB) decrease significantly the antibacterial effect of both PLA 2. In conclusion, BthTx I and BthTX II caused renal alteration and presented activity antimicrobial. The indomethacin was able to antagonize totally the renal effects induced by BthTx I and partially the effects promoted by BthTx II, suggesting involvement of inflammatory mediators in

Research paper thumbnail of High Salt Intake Promotes Different Responses to Urodilatin and Uroguanylin in the Isolated Rat Kidney

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, Jan 12, 2017

Urodilatin (UD) and uroguanylin (UGN) have been implicated in the regulation of salt and water ho... more Urodilatin (UD) and uroguanylin (UGN) have been implicated in the regulation of salt and water homeostasis, particularly in the balance handling of salt intake. In this sense, the aim of the present work was to study the main effects of these peptides in kidneys from animals subjected to high NaCl (2%) intake, during 10 days in metabolic cages. The control group received only normal water, whereas the treated group drank 2% solution of NaCl (NaCl 2%). In addition, we studied effect of subthreshold UD (0.14 nM) and UGN (0.06 μM) doses in NaCl 2% after a 30-min control period. Kidney perfusion was performed with Krebs-Henseleit containing 6 g% bovine albumin previously dialyzed. The effects of UD (0.14 nM) promoted reduction of PP, RVR, and UF in the NaCl 2% group. We also observed an increase in %TNa+ and %TCl-. The main effects of UGN in NaCl 2% were increase in PP, UF, and GFR, followed by a reduction in %TNa+ and %TCl-. After an increased intake of salt, physiological pathways are...

Research paper thumbnail of Pulmonary mechanic and lung histology induced by Crotalus durissus cascavella snake venom

Toxicon : official journal of the International Society on Toxinology, 2017

This study have analyzed the pulmonary function in an experimental model of acute lung injury, in... more This study have analyzed the pulmonary function in an experimental model of acute lung injury, induced by the Crotalus durissus cascavella venom (C. d. cascavella) (3.0 μg/kg - i.p), in pulmonary mechanic and histology at 1 h, 3 h, 6 h, 12 h and 24 h after inoculation. The C. d. cascavella venom led to an increase in Newtonian Resistance (RN), Tissue Resistance (G) and Tissue Elastance (H) in all groups when compared to the control, particularly at 12 h and 24 h. The Histeresivity (η) increased 6 h, 12 h and 24 h after inoculation. There was a decrease in Static Compliance (CST) at 6 h, 12 h and 24 h and inspiratory capacity (IC) at 3 h, 6 h, 12 h and 24 h. C. d. cascavella venom showed significant morphological changes such as atelectasis, emphysema, hemorrhage, polymorphonuclear inflammatory infiltrate, edema and congestion. After a challenge with methacholine (MCh), RN demonstrated significant changes at 6, 12 and 24 h. This venom caused mechanical and histopathological changes i...

Research paper thumbnail of Renal effects of Bunodosoma caissarum crude extract: Prostaglandin and endothelin involvement

Toxicon : official journal of the International Society on Toxinology, Jan 23, 2017

Sea anemones contain a variety of interesting biologically active compounds, including some poten... more Sea anemones contain a variety of interesting biologically active compounds, including some potent toxins. PLA2 from Bunodosoma caissarum, a sea anemone endemic in the Brazilian southern coast, has shown renal alterations on isolated kidney. The aim of this study was to evaluate the renal and vascular effects of B. caissarum crude extract (BcE) on isolated perfused kidney and arteriolar mesenteric bed, as well the involvement of prostaglandins and endothelin. BcE did not show any effect on arteriolar mesenteric bed, but increased perfusion pressure, renal vascular resistance, urinary flow, glomerular filtration rate and decreased the percentage of sodium tubular transport on isolated perfused kidney. Indomethacin blocked the renal effects induced by BcE and tezosentan only partially blocked these effects. These results demonstrate the effects of BcE on kidney in situ, suggesting the involvement of prostaglandins and endothelin.

Research paper thumbnail of Differences between renal effects of venom from two Bothrops jararaca populations from southeastern and southern Brazil

Toxicon, 2016

Components from animal venoms may vary according to the snake&amp... more Components from animal venoms may vary according to the snake's age, gender and region of origin. Recently, we performed a proteomic analysis of Bothrops jararaca venom from southern (BjSv) and southeastern (BjSEv) Brazil, showing differences in the venom composition, as well as its biological activity. To continue the study, we report in this short communication the different effects induced by the BjSEv and BjSv on isolated kidney and MDCK renal cells. BjSEv decreased perfusion pressure (PP) and renal vascular resistance (RVR) and increased urinary flow (UF) and glomerular filtration rate (GFR), while BjSv did not alter PP and RVR and reduced UF and GFR. Both types of venom, more expressively BjSEv, reduced %TNa(+), %TK(+) and %Cl(-). In MDCK cells, the two types of venom showed cytotoxicity with IC50 of 1.22 μg/mL for BjSv and 1.18 μg/mL for BjSEv and caused different profiles of cell death, with BjSv being more necrotic. In conclusion, we suggest that BjSv is more nephrotoxic than BjSEv.

Research paper thumbnail of Toxins Polypeptide That Interfere with the Flow of Calcium (Channels and Receptors Intra and Extra-Cellular)

Sciprints, 2016

The voltage-dependent calcium channels (Cav) are a family of multigene channel that plays an esse... more The voltage-dependent calcium channels (Cav) are a family of multigene channel that plays an essential role in regulating a variety of cellular functions. These channels are categorized as type L-, N-, P / Q-, R- or T, based on their electrophysiological and pharmacological properties. Activation of these channels and Ca2 + entry is required in many physiological processes such as muscle contraction and release of hormones and neurotransmitters, and many others, for example in the contraction mechanism, and vascular relaxation.