Pathological changes induced by BaH1, a hemorrhagic proteinase isolated from Bothrops asper (Terciopelo) snake venom, on mouse capillary blood vessels

Moreira, Lisela; Borkow, Gadi; Ovadia, Michael; Gutiérrez, José Marı́a

doi:10.1016/0041-0101(94)90376-x

Cited by 73 publications

(34 citation statements)

References 21 publications

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“…This is the Wrst immunohistochemical demonstration of in vivo BM degradation by snake venom hemorrhagic SVMPs. The loss of endothelial cell markers evidences a drastic endothelial pathology, in agreement with ultrastructural studies on the action of hemorrhagic SVMPs showing prominent alterations, leading to endothelial cell disruption, that occur within minutes of SVMP injection [40][41][42]. On the other hand, both qualitative and quantitative (i.e., capillary:muscle cell ratio) assessments revealed a conspicuous reduction in the immunostaining of BM antigens in capillaries upon treatment with hemorrhagic doses of these SVMPs.…”

Section: Discussionsupporting

confidence: 61%

“…wall tension and shear stress, provoke a distention in the capillary wall until its integrity is disrupted and extravasation occurs in an explosive fashion [7,42]. In the light of this hypothesis, it is suggested that such abrupt distention and rupture results in the loss of integrity not only of endothelial cells, but also of BM components, as observed at the ultrastructural level [41,42]. In agreement with this hypothesis, no evident ultrastructural changes occur in the BM of capillaries in tissue injected with BaP1 when blood Xow was abrogated [42].…”

Section: Discussionmentioning

confidence: 99%

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Novel insights into capillary vessel basement membrane damage by snake venom hemorrhagic metalloproteinases: A biochemical and immunohistochemical study

Escalante

Shannon

Moura-da-Silva

et al. 2006

Archives of Biochemistry and Biophysics

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The hemorrhagic activity characteristic of viperid snake envenomations is due to the action of venom metalloproteinases (SVMPs) on the capillary vessel basement membrane (BM). This study compared the action of two SVMPs on BM in vitro (degradation of Matrigel) and in vivo (immunohistochemical assessment of BM markers in mouse gastrocnemius muscle). SVMPs BaP1 (belonging to the P-I class) and jararhagin (of the P-III class) had a similar proteolytic activity on azocasein and degraded Matrigel with a slightly diVerent cleavage pattern, since BaP1 exerted a limited proteolysis of both laminin and nidogen, whereas jararhagin predominantly degraded nidogen. In contrast with this pattern of limited proteolysis of BM proteins observed in vitro, immunohistochemical analysis of laminin, nidogen and type IV collagen, as well as of the endothelial cell marker VEGFR-2, in the hemorrhagic areas in the muscle, revealed a pronounced reduction in the immunostaining of these three BM components, associated with a loss of the endothelial cell marker. BM of muscle Wbers was aVected to a lesser extent. In conclusion, in vitro results demonstrated that SVMPs induce a pattern of limited proteolysis on BM components. The drastic loss of these antigens in aVected capillaries in vivo is likely to depend on the combination of limited proteolysis of BM and the action of hemodynamic biophysical forces, previously shown to play a role in SVMP-induced capillary damage, which may cause a mechanical disruption of BM structure.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Novel insights into capillary vessel basement membrane damage by snake venom hemorrhagic metalloproteinases: A biochemical and immunohistochemical study

Escalante

Shannon

Moura-da-Silva

et al. 2006

Archives of Biochemistry and Biophysics

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“…[14][15][16][17][18][19] Moreover, various muscle-damaging toxins and hemorrhagic toxins have been isolated and characterized from this venom. 20,21 Hemorrhagic metalloproteinases play a relevant role in the pathogenesis of local tissue damage in pit viper envenomations, since besides hemorrhage, [22][23][24] they induce edema, 25 myonecrosis, 24,[26][27][28] and skin damage. 19 Therefore, inhibition of venom metalloproteinases may significantly reduce the extent of pit viperinduced local tissue damage.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of local hemorrhage and dermonecrosis induced by Bothrops asper snake venom: effectiveness of early in situ administration of the peptidomimetic metalloproteinase inhibitor batimastat and the chelating agent CaNa2EDTA.

Rucavado¹,

Escalante²,

Franceschi³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

110

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Abstract. The effectiveness of the chelating agent CaNa 2 EDTA and the peptidomimetic matrix metalloproteinase inhibitor batimastat (BB-94) to inhibit local tissue damage induced by Bothrops asper snake venom was studied in mice. Both compounds totally inhibited proteolytic, hemorrhagic, and dermonecrotic effects, and partially reduced edema-forming activity, when incubated with venom prior to injection. Much lower concentrations of batimastat than of CaNa 2 EDTA were required to inhibit these effects. In addition, batimastat, but not CaNa 2 EDTA, partially reduced myotoxic activity of the venom. When the inhibitors were administered at various time intervals after envenomation at the same site of venom injection, both compounds were effective in neutralizing local hemorrhage and dermonecrosis if administered rapidly after venom. Inhibition was not as effective as the time lapse between venom and inhibitor injections increased. Owing to the relevance of metalloproteinases in the pathogenesis of local tissue damage induced by B. asper and other pit viper venoms, it is suggested that administration of peptidomimetic metalloproteinase inhibitors or CaNa 2 EDTA at the site of venom injection may represent a useful alternative to complement antivenoms in the neutralization of venom-induced local tissue damage.

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“…After neuwiedase injection, skeletal muscle showed conspicuous damage of muscle fibers without any evidence of hemorrhage. This effect is characterized by alterations of cell plasma membrane and mitochondrial swelling, characteristic features of cell death (20). In addition, disruption of the basement membrane, which surrounds each muscle fiber, was also observed.…”

Section: Discussionmentioning

confidence: 98%

Action of neuwiedase, a metalloproteinase isolated from Bothrops neuwiedi venom, on skeletal muscle: an ultrastructural and immunocytochemistry study

Baldo

Ferreira²,

Lopes

et al. 2010

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

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Abstract:The damaging effects of neuwiedase, a non-hemorrhagic snake venom metalloproteinase from P-I class, on gastrocnemius muscle are studied herein. Following neuwiedase injection, ultrastructural alterations were detected early showing disarrangement of skeletal muscle fibers (characterized by discontinuity of Z lines), mitochondrial swelling, and disruption of plasma membrane and basal lamina. Degradation of skeletal muscle and the appearance of an amorphous substance, primarily composed of cellular debris, were noted after 24 hours. The presence of neuwiedase at the injection site (detected by immunocytochemistry) revealed highly specific labeling of myofibril components of damaged myocytes. In addition, proteolysis of muscle proteins assayed through myofibrils extracted from gastrocnemius muscle indicated that neuwiedase provoked degradation of myofibrils, especially myosin. These results suggest that skeletal muscle damage, induced by neuwiedase, is probably due to its proteolytic action on myofibrils, which are responsible for the maintenance of the cellular architecture.

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Pathological changes induced by BaH1, a hemorrhagic proteinase isolated from Bothrops asper (Terciopelo) snake venom, on mouse capillary blood vessels

Cited by 73 publications

References 21 publications

Novel insights into capillary vessel basement membrane damage by snake venom hemorrhagic metalloproteinases: A biochemical and immunohistochemical study

Novel insights into capillary vessel basement membrane damage by snake venom hemorrhagic metalloproteinases: A biochemical and immunohistochemical study

Inhibition of local hemorrhage and dermonecrosis induced by Bothrops asper snake venom: effectiveness of early in situ administration of the peptidomimetic metalloproteinase inhibitor batimastat and the chelating agent CaNa2EDTA.

Action of neuwiedase, a metalloproteinase isolated from Bothrops neuwiedi venom, on skeletal muscle: an ultrastructural and immunocytochemistry study

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