The origin of the diversity of crotoxin isoforms in the venom of <i>Crotalus durissus terrificus</i>

Faure, Grazyna; Choumet, Valérie; Bouchier, Christiane; Camoin, Luc; Guillaume, Jean‐Luc; Monegier, B.; Vuilhorgne, Marc; Bon, Cassian

doi:10.1111/j.1432-1033.1994.tb18978.x

Cited by 108 publications

(66 citation statements)

References 17 publications

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“…In support of Coagulation disturbances (19,20) leading to fibrin deposition and ischemia, mainly through the action of the thrombin-like enzyme (gyroxin) of this venom (8,9,19) could also contribute to the hepatic damage registered in the present study. In addition, considering the inter-and intrasubspecific variation in the composition and biological activities of this venom (51,(56)(57)(58)(59)(60)(61), there may be differences in hepatic The present study provides evidence that Crotalus durissus terrificus venom induces hepatotoxicity in rats, by increasing blood liver enzymes, probably derived from liver, since histological analysis revealed augmented endothelium density and hepatic damage.…”

Section: Discussionmentioning

confidence: 61%

Acute hepatotoxicity of Crotalus durissus terrificus (South American rattlesnake) venom in rats

França¹,

Ferrari²,

Souza³

et al. 2009

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

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Venom of the South American rattlesnake, Crotalus durissus terrificus (Cdt), presents myotoxic and neurotoxic outcomes, but reports on its effects on the liver are scarce. This study examined the hepatotoxicity resulting from Cdt venom administration (100, 200 and 300 μg/kg) in male Wistar rats. Animals were studies at 3, 6, 9 and 12 hours after venom injection. The hepatotoxicity was assessed through serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma glutamyl transferase (GGT), bilirrubin and also by histopathological evaluation. All the different concentrations of Cdt venom resulted in increased levels of hepatic enzymes, when compared with the control group, except for the 100 μg/kg dose, which presented normal levels at 9 and 12 hours after venom administration. Bilirrubin levels remained unchanged by Cdt venom. Histological analysis revealed endothelial damage, inflammatory cell infiltration, as well as sinusoidal and portal congestion. Based on these observations, we may conclude that Cdt venom causes dose-and time-dependent hepatic damage in rats, characterized by elevated hepatic enzyme levels and histological alterations.

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Section: Discussionmentioning

confidence: 61%

Acute hepatotoxicity of Crotalus durissus terrificus (South American rattlesnake) venom in rats

França¹,

Ferrari²,

Souza³

et al. 2009

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

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“…There are several crotoxin isoforms that may result from a random association between PLA 2 and Crpt (34). This multiplicity and diversity of crotoxin isoforms appear to result from either a post-translational modification of a unique precursor of crotoxin or expression of different mRNA (35).…”

Section: Discussionmentioning

confidence: 99%

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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“…These findings suggested that the crotoxin isoforms from Crotalus durissus collilineatus probably plays an important role in this venomÕs action (Ponce-Soto, 2002). Several studies have shown that the venom of Crotalus durissus terrificus contains various isoforms of PLA 2 Bon, 1987, 1988;Faure, 1991Faure, , 1993Faure, , 1994. In this work, we describe the biochemical and pharmacological characterization of a new crotoxin B isoform PLA 2 (F6a) of crotoxin B from Crotalus durissus collilineatus.…”

Section: Introductionmentioning

confidence: 99%

“…Crotoxin exists in several isoforms, which vary in their biological activity, probably as a result of the heterogeneity in the PLA 2 and crotapotins (Faure and Bon, 1987). The multiplicity and diversity of crotoxin isoforms may be due to post-translational modification of a unique precursor of crotoxin or from the expression of different mRNAs Bon, 1987, 1988;Faure, 1991Faure, , 1993Faure, , 1994.…”

Section: Introductionmentioning

confidence: 99%

Biological and Structural Characterization of Crotoxin and New Isoform of Crotoxin B PLA2 (F6a) from Crotalus durissus collilineatus Snake Venom

et al. 2007

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A new crotoxin B isoform PLA 2 (F6a), from Crotalus durissus collilineatus was purified from by one step reverse phase HPLC chromatography using l-Bondapack C-18 column analytic. The new crotoxin B isoform PLA 2 (F6a), complex crotoxin, the catalytic subunit crotoxin B isoform PLA 2 (F6a) and two crotapotin isoforms (F3 and F4), were isolated from the venom of Crotalus durissus collilineatus. The crotapotins isoforms F3 and F4 had similar chemical properties, the two proteins different in their ability to inhibit of isoforms of PLA 2 (F6 and F6a). The molecular masses estimated by MALDI-TOF mass spectrometry were: crotoxin B: 14,943.14 Da, crotapotin F3: 8,693.24 Da, and crotapotin F4: 9 314.56 Da. The new crotoxin B isoform PLA 2 (F6a) contained 122 amino acid residues and a pI of 8.58. Its amino acid sequence presents high identity with those of other PLA 2 s, particularly in the calcium binding loop and active site helix 3. It also presents similarities in the C-terminal region with other myotoxic PLA 2 s. The new crotoxin B isoform PLA 2 (F6a) contained 122 amino acid residues, with a primary structure of HLLQFNKMIK FETRRNAIPP YAFYGCYCGW GGRGRPKDAT DRCCFVHDCC YGKLAKCNTK WDFYRYSLKS GYITCGKGTW CEEQICECDR VAAECLRRSL STYRYGYMIY PDSRCRGPSE TC. A neuromuscular blocking activity was induced by crotoxin and new crotoxin B isoform PLA 2 (F6a) in the isolated mouse phrenic nerve diaphragm and the biventer cervicis chick nerve-muscle preparation. Whole crotoxin was devoid of cytolytic activity upon myoblasts and myotubes in vitro, whereas new crotoxin B isoform PLA 2 (F6a) was clearly cytotoxic to these cells.

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The origin of the diversity of crotoxin isoforms in the venom of Crotalus durissus terrificus

Cited by 108 publications

References 17 publications

Acute hepatotoxicity of Crotalus durissus terrificus (South American rattlesnake) venom in rats

Acute hepatotoxicity of Crotalus durissus terrificus (South American rattlesnake) venom in rats

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

Biological and Structural Characterization of Crotoxin and New Isoform of Crotoxin B PLA2 (F6a) from Crotalus durissus collilineatus Snake Venom

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