Comparison of the biological activities in venoms from three subspecies of the South American rattlesnake (Crotalus durissus terrificus, C. durissus cascavella and C. durissus collilineatus)

Santoro, Marcelo Larami; Sousa-e-Silva, Maria Cristina Cirillo; Gonçalves, L.R.C.; Almeida‐Santos, Selma Maria; Cardoso, Débora Morais; Laporta-Ferreira, I. L.; Saiki, M.; Peres, Celeide Pinto Aguiar; Sano-Martins, Ida Sigueko

doi:10.1016/s0742-8413(98)10079-8

Cited by 66 publications

(61 citation statements)

References 41 publications

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“…Analysis of crotoxin on the ES-MS/MS revealed the presence of two main fractions, Crpt and sPLA 2 , with respective molecular masses of 9.64 kDa and 14.65 kDa, and two additional peaks of 25.50 and 29.30 kDa. These results showed a strong correlation with the electrophoretic profile observed for crotoxin, given that the dimer formed by association of crotapotin and sPLA 2 has a molecular mass of 25.50 kDa as confirmed by the third FLPC peak.…”

Section: Isolation and Purification Of Crotoxin From The Cdcmvmentioning

confidence: 99%

“…On the other hand, since sPLA 2 presented a molecular mass of 14.65 kDa, the fraction with a molecular weight of 29.30 may reflect an interaction of two sPLA 2 peaks (Figure 2 -A). The molecular exclusion HPLC profile of sPLA 2 :Crtp, sPLA 2 and Crpt is shown in Figure 2 -B. The chromatographic PLA 2 profile revealed two main fractions, one representative of a monomeric form of PLA 2 and the other of a PLA 2 homodimer.…”

Section: Isolation and Purification Of Crotoxin From The Cdcmvmentioning

confidence: 99%

“…The rattlesnake Crotalus durissus has a widespread distribution in South and Central America, where 14 subspecies have been described (2). Accidents involving species of the genus Crotalus are usually serious and frequently fatal in the absence of specific and adequate treatment, mainly due to acute renal failure (3,4).…”

Section: Introductionmentioning

confidence: 99%

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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

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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.

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Section: Isolation and Purification Of Crotoxin From The Cdcmvmentioning

confidence: 99%

Section: Isolation and Purification Of Crotoxin From The Cdcmvmentioning

confidence: 99%

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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

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“…The genus Crotalus contains several species of snakes responsible for high morbidity and mortality rates (1). Crotalus durissus cascavella is a snake usually found in the scrubland of the Brazilian Northeast (2).…”

Section: Introductionmentioning

confidence: 99%

Thalidomide and pentoxifylline block the renal effects of supernatants of macrophages activated with Crotalus durissus cascavella venom

Martins

Nobre

Almeida

et al. 2004

Braz J Med Biol Res

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Because thalidomide and pentoxifylline inhibit the synthesis and release of tumor necrosis factor-α (TNF-α), we determined the effect of these drugs on the renal damage induced by supernatants of macrophages activated with Crotalus durissus cascavella venom in order to identify the role of TNF-α in the process. Rat peritoneal macrophages were collected with RPMI medium and stimulated in vitro with C.d. cascavella venom (10 µg/ml) in the absence and presence of thalidomide (15 µM) or pentoxifylline (500 µM) for 1 h and washed and kept in culture for 2 h. Supernatant (1 ml) was tested on an isolated perfused rat kidney (N = 6 for each group). The first 30 min of each experiment were used as control. The supernatant was added to the perfusion system. All experiments lasted 120 min. The toxic effect of the preparation of venom-stimulated macrophages on renal parameters was determined. At 120 min, thalidomide (Thalid) and pentoxifylline (Ptx) inhibited (P < 0.05) the increase in perfusion pressure caused by the venom (control = 114.0 ± 1.3; venom = 137.1 ± 1.5; Thalid = 121.0 ± 2.5; Ptx = 121.4 ± 4.0 mmHg), renal vascular resistance (control = 4.5 ± 0.2; venom = 7.3 ± 0.6; Thalid = 4.5 ± 0.9; Ptx = 4.8 ± 0.6 mmHg/ml g -1 min -1 ), urinary flow (control = 0.23 ± 0.001; venom = 0.44 ± 0.01; Thalid = 0.22 ± 0.007; Ptx = 0.21 ± 0.009 ml g -1 min -1 ), glomerular filtration rate (control = 0.72 ± 0.06; venom = 1.91 ± 0.11; Thalid = 0.75 ± 0.04; Ptx = 0.77 ± 0.05 ml g -1 min -1 ) and the decrease in percent tubular sodium transport (control = 77.0 ± 0.9; venom = 73.9 ± 0.66; Thalid = 76.6 ± 1.1; Ptx = 81.8 ± 2.0%), percent tubular chloride transport (control = 77.1 ± 1.2; venom = 71.4 ± 1.1; Thalid = 77.6 ± 1.7; Ptx = 76.8 ± 1.2%), and percent tubular potassium transport (control = 72.7 ± 1.1; venom = 63.0 ± 1.1; Thalid = 72.6 ± 1.0; Ptx = 74.8 ± 1.0%), 30 min before and during the stimulation of macrophages with C.d. cascavella venom. These data suggest the participation of TNF-α in the renal effects induced by supernatant of macrophages activated with C.d. cascavella venom.

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“…In Brazil, the genus Crotalus contains several species and subspecies of snakes responsible for approximately 1500 cases of snakebite annually (Santoro et al 1999). Crotalus durissus cascavella (C.d.…”

mentioning

confidence: 99%

Renal Effects of Supernatant from Macrophages Activated by Crotalus durissus cascavella Venom: The Role of Phospholipase A₂ and Cyclooxygenase

Martins

Lima²,

Toyama

et al. 2003

Pharmacology & Toxicology

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In Brazil, the genus Crotalus is responsible for approximately 1500 cases of snakebite annually. The most common complication in the lethal cases is acute renal failure, although the mechanisms of the damaging effects are not totally understood. In this work, we have examined the renal effects caused by a supernatant of macrophages stimulated by Crotalus durissus cascavella venom as well as the potential role of phospholipase A 2 and cyclo-oxygenase. Rat peritoneal macrophages were collected and placed in a RPMI medium and stimulated by crude Crotalus durissus cascavella venom (1, 3 or 10 mg/ml) for 1 hr. They were then washed and kept in a culture for 2 hr. The supernatant (1 ml) was tested in an isolated perfused rat kidney. The first 30 min. of each experiment were used as an internal control, and the supernatant was added to the system after this period. All experiments lasted 120 min. A study of toxic effect on perfusion pressure, glomerular filtration rate, urinary flow, percent of sodium tubular transport and percent of proximal tubular sodium transport was made. The lowest concentration of venom (1 mg/ml) was not statistically different from the control values. The most intense effects were seen at 10 mg/ml for all renal parameters. The infusion of the supernatant of macrophages stimulated with crude venom (3 or 10 mg/ml) increased the perfusion pressure, glomerular filtration rate and urinary flow, decreased the percent of sodium tubular transport and percent of proximal tubular sodium transport. Dexamethasone (10 mM) and quinacrine (10 mM) provided protection against the effect of the venom on glomerular filtration rate, urinary flow, percent of sodium tubular transport, percent of proximal tubular sodium transport and perfusion pressure. Indomethacin (10 mM) and nordiidroguaretic acid (1 mM) reversed almost all functional changes, except those of the perfusion pressure. These results suggest that macrophages stimulated with Crotalus durissus cascavella venom release mediators capable of promoting nephrotoxicity in vitro. Moreover, phospholipase A 2 and cyclooxygenase products are involved in these biologic effects.

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Comparison of the biological activities in venoms from three subspecies of the South American rattlesnake (Crotalus durissus terrificus, C. durissus cascavella and C. durissus collilineatus)

Cited by 66 publications

References 41 publications

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

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

Thalidomide and pentoxifylline block the renal effects of supernatants of macrophages activated with Crotalus durissus cascavella venom

Renal Effects of Supernatant from Macrophages Activated by Crotalus durissus cascavella Venom: The Role of Phospholipase A₂ and Cyclooxygenase

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Comparison of the biological activities in venoms from three subspecies of the South American rattlesnake (Crotalus durissus terrificus, C. durissus cascavella and C. durissus collilineatus)

Cited by 66 publications

References 41 publications

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

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

Thalidomide and pentoxifylline block the renal effects of supernatants of macrophages activated with Crotalus durissus cascavella venom

Renal Effects of Supernatant from Macrophages Activated by Crotalus durissus cascavella Venom: The Role of Phospholipase A2 and Cyclooxygenase

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Renal Effects of Supernatant from Macrophages Activated by Crotalus durissus cascavella Venom: The Role of Phospholipase A₂ and Cyclooxygenase