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

Barbosa, Paula; Martins, Alice Maria Costa; Alves, Renata; Amora, Daniela Nascimento; Martins, René Duarte; Toyama, Marcos H.; Havt, Alexandre; Nascimento, Nilberto R.F.; Rocha, Vera Lúcia; Menezes, Dalgimar Beserra de; Fonteles, M. C.; Monteiro, Helena Serra Azul

doi:10.1016/j.toxicon.2006.01.012

Cited by 12 publications

(8 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly to other Lys49-PLA2s, such as PrTx-I, PrTx-II [25] and BthTx-I [21], BjVIII does not show significant enzymatic activity and induces similar myonecrosis as BthTx-I, when assayed at the same conditions as Barbosa et al [26]. However, an atypical effect presented by BjVIII, and not by other Lys49-PLA2s, is a strong human platelet aggregation activity.…”

Section: Resultsmentioning

confidence: 66%

Purification and Preliminary Crystallographic Analysis of a New Lys49-PLA2 from B. Jararacussu

Santos

Fagundes

Teixeira

et al. 2008

IJMS

View full text Add to dashboard Cite

BjVIII is a new myotoxic Lys49-PLA2 isolated from Bothrops jararacussu venom that exhibits atypical effects on human platelet aggregation. To better understand the mode of action of BjVIII, crystallographic studies were initiated. Two crystal forms were obtained, both containing two molecules in the asymmetric unit (ASU). Synchrotron radiation diffraction data were collected to 2.0Å resolution and 1.9Å resolution for crystals belonging to the space group P 2 1 2 1 2 1 (a = 48.4Å, b = 65.3Å, c = 84.3Å) and space group P 3 1 21 (a = b = 55.7Å, c = 127.9Å), respectively. Refinement is currently in progress and the refined structures are expected to shed light on the unusual platelet aggregation activity observed for BjVIII.

show abstract

Section: Resultsmentioning

confidence: 66%

Purification and Preliminary Crystallographic Analysis of a New Lys49-PLA2 from B. Jararacussu

Santos

Fagundes

Teixeira

et al. 2008

IJMS

View full text Add to dashboard Cite

show abstract

“…Two general hypotheses should be considered to explain this effect: the venom may induce a diminished release of an inhibitory endothelial factor, such as nitric oxide (NO) or endothelium-derived hyperpolarizing factors (EDHF); or the venom may promote the endothelial release of a vasoconstrictor factor, for example, endothelin. As a matter of fact, we have previously demonstrated that renal effects promoted by Bothrops moojeni myotoxin-I were due to release of renal endothelin (29). Furthermore, vasoconstrictor peptides have been found in some viper venoms including the inhibitory peptides sarafotoxin and bradykinin (30).…”

Section: Discussionmentioning

confidence: 98%

Renal and vascular effects of Crotalus durissus cumanensis venom and its crotoxin fraction

Pereira¹,

Menezes²,

Torres³

et al. 2011

J. Venom. Anim. Toxins incl. Trop. Dis

View full text Add to dashboard Cite

Abstract:In this study, we evaluated the actions of Crotalus durissus cumanensis venom (CDCmV), and its crotoxin (Crtx) fraction, on renal and vascular functions in Wistar rats. In isolated perfused kidneys, CDCmV (10 µg/mL) significantly increased the perfusion pressure (PP) from 110.7 ± 2.4 to 125.3 ± 2.8 mmHg after 30 minutes. This effect was accompanied by an increased renal vascular resistance (RVR) from 5.4 ± 0.1 to 6.2 ± 0.2 mmHg/mL.g ). Both CDCmV and Crtx reduced the percentage of tubular transport of sodium, chloride and potassium. The cytotoxicity of these substances against MDCK cells was tested by the MTT method: only CDCmV caused a decrease in the cell viability with an IC 50 of 5.4 µg/mL. In endothelium-intact isolated aortic rings, CDCmV (0.1 to 30 µg/mL) increased the sustained phenylephrineinduced contraction to a value of 130.0 ± 6.6% of its corresponding control, but showed a relaxant effect in endothelium-denuded preparations. Similar results were observed in aortic rings contracted with potassium (40 mM). Crtx was ineffective in aortic ring assays. Thus, it is reasonable to suggest that the renal effects induced by the CDCmV may be due to its influence on the endothelium's ability to release factors that can alter the contractile behavior of vascular smooth muscle. In conclusion, CDCmV is toxic to kidney cells. It changes parameters of the renal function including the glomerular filtration rate, renal vascular resistance and tubular transport. The actions induced by CDCmV also involve endothelium-dependent vasoactive properties. Their effects may be only partially attributed to Crtx.

show abstract

“…Barbosa et al [3] also showed that BmTx-I, a Lys49-PLA 2 myotoxin of the snake Bothrops moojeni, promotes renal alterations similar to those promoted by BthTx-I. Tezosentan inhibited renal alterations induced by BmTx-I in UF, GFR and sodium, potassium and chloride tubular transports, suggesting a role for endotelin in renal pathophysiologic changes induced by this toxin [3]. These findings are particularly relevant to the present study, since toad bladder is a structure whose transport characteristics and response to hormones and drugs resemble those from the mammalian distal nephron [16][17].…”

Section: Methodsmentioning

confidence: 99%

“…Local myonecrosis may induce permanent tissue loss, physical disability and limb amputation; while widespread systemic myotoxicity may lead to myoglobinuria and acute renal failure, which is a frequent cause of death in snakebite victims [1]. Some mechanisms have been suggested to explain renal damage caused by snake venoms, including a direct nephrotoxic effect, disseminated intravascular coagulation, and release of vasoactive substances [2][3]. Despite such findings, the mechanisms involved in the pathogenesis of renal alterations induced by snake venoms remain unclear.…”

Section: Introductionmentioning

confidence: 99%

“…Venoms from snakes of the family Viperidae contain group IIA PLA 2 s. This group of PLA 2 is subdivided into two types: Asp49-PLA 2 s, which have an aspartic acid residue at position 49 and show high catalytic activity; and Lys49-PLA 2 s, which have a lysine residue at position 49 and show low or no catalytic activity [1]. In spite of their low enzymatic activity, Lys49-PLA 2 s perform several pharmacological activities, such as nephrotoxicity, myotoxicity, neurotoxicity, cytotoxicity, among others [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The role of extracellular calcium in the effect of a snake venom Lys49-phospholipase A<sub>2</sub> on water transport across epithelial membranes

Leite¹,

Franco²,

Selistre-de-Araújo³

2011

JBPC

View full text Add to dashboard Cite

ACLMT is a Lys49-phospholipase A 2 myotoxin isolated from the venom of the Agkistrodon contortrix laticinctus snake. This study investigated the mechanisms involved in effect of ACLMT on membrane water permeability by examining the role of extracellular calcium and strontium in this effect. Water flow across the membrane was gravimetrically measured in bladder sac preparations. The decrease in extracellular calcium promoted a higher response of epithelium to ACLMT, suggesting that the extracellular calcium protects the membrane from the action of the toxin. No alteration in the effect of the toxin on water transport was observed when calcium was replaced by strontium, indicating that this effect is independent of its enzymatic activity. These findings may bring an important contribution towards the comprehension of the mechanisms involved in the effect of Lys49-phospholipase A 2 myotoxins on water permeability of epithelial membranes, with implications for the understanding of renal toxicity.

show abstract

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

Cited by 12 publications

References 34 publications

Purification and Preliminary Crystallographic Analysis of a New Lys49-PLA2 from B. Jararacussu

Purification and Preliminary Crystallographic Analysis of a New Lys49-PLA2 from B. Jararacussu

Renal and vascular effects of Crotalus durissus cumanensis venom and its crotoxin fraction

The role of extracellular calcium in the effect of a snake venom Lys49-phospholipase A<sub>2</sub> on water transport across epithelial membranes

Contact Info

Product

Resources

About

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

Cited by 12 publications

References 34 publications

Purification and Preliminary Crystallographic Analysis of a New Lys49-PLA2 from B. Jararacussu

Purification and Preliminary Crystallographic Analysis of a New Lys49-PLA2 from B. Jararacussu

Renal and vascular effects of Crotalus durissus cumanensis venom and its crotoxin fraction

The role of extracellular calcium in the effect of a snake venom Lys49-phospholipase A&lt;sub&gt;2&lt;/sub&gt; on water transport across epithelial membranes

Contact Info

Product

Resources

About

The role of extracellular calcium in the effect of a snake venom Lys49-phospholipase A<sub>2</sub> on water transport across epithelial membranes