Toxins Are an Excellent Source of Therapeutic Agents against Cardiovascular Diseases

Koh, Cho Yeow; Modahl, Cassandra M.; Kulkarni, Namrata Pramod; Kini, R. Manjunatha

doi:10.1055/s-0038-1661384

Cited by 18 publications

(9 citation statements)

References 228 publications

(213 reference statements)

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“…Fibrinogenolysis is a toxic effect described for Crotalus spp. and is generated by SVMPs and SVSPs [33,97]. These assays were performed to demonstrate A) the capacity of the venoms to hydrolyze fibrinogen and B) the role of SVMPs and SVSPs during this process.…”

Section: Fibrinogenolytic Activitymentioning

confidence: 99%

Functional Mining of the Crotalus Spp. Venom Protease Repertoire Reveals Potential for Chronic Wound Therapeutics

et al. 2020

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Chronic wounds are a major health problem that cause millions of dollars in expenses every year. Among all the treatments used, active wound treatments such as enzymatic treatments represent a cheaper and specific option with a fast growth category in the market. In particular, bacterial and plant proteases have been employed due to their homology to human proteases, which drive the normal wound healing process. However, the use of these proteases has demonstrated results with low reproducibility. Therefore, alternative sources of proteases such as snake venom have been proposed. Here, we performed a functional mining of proteases from rattlesnakes (Crotalus ornatus, C. molossus nigrescens, C. scutulatus, and C. atrox) due to their high protease predominance and similarity to native proteases. To characterize Crotalus spp. Proteases, we performed different protease assays to measure and confirm the presence of metalloproteases and serine proteases, such as the universal protease assay and zymography, using several substrates such as gelatin, casein, hemoglobin, L-TAME, fibrinogen, and fibrin. We found that all our venom extracts degraded casein, gelatin, L-TAME, fibrinogen, and fibrin, but not hemoglobin. Crotalus ornatus and C. m. nigrescens extracts were the most proteolytic venoms among the samples. Particularly, C. ornatus predominantly possessed low molecular weight proteases (P-I metalloproteases). Our results demonstrated the presence of metalloproteases capable of degrading gelatin (a collagen derivative) and fibrin clots, whereas serine proteases were capable of degrading fibrinogen-generating fibrin clots, mimicking thrombin activity. Moreover, we demonstrated that Crotalus spp. are a valuable source of proteases that can aid chronic wound-healing treatments.

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Section: Fibrinogenolytic Activitymentioning

confidence: 99%

Functional Mining of the Crotalus Spp. Venom Protease Repertoire Reveals Potential for Chronic Wound Therapeutics

et al. 2020

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“…GPIIb/IIIa inhibitors such as tirofiban and eptifibatide (fiban) are synthetic small molecules that mimic or contain an arginine-glycine-aspartic acid (RGD) motif and are thus able to bind the RGD recognition site on GPIIb/IIIa. 55 Due to this peculiar property, they are also called ligand-mimetic GPIIb/IIIa inhibitors. The binding of RGD mimetic compounds apparently induces a conformational change in GPIIb/IIIa, which then result in the emergence of cryptic integrin domains recognizable by specific antibodies.…”

Section: Gpiib/iiia Inhibitorsmentioning

confidence: 99%

Drug-Induced Thrombocytopenia: Mechanisms and Laboratory Diagnostics

Danese

Montagnana

Favaloro

et al. 2019

Semin Thromb Hemost

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Thrombocytopenia is a condition characterized by a decreased number of platelets in peripheral blood, which can be caused by a myriad of both congenital and acquired disorders. Drug-induced thrombocytopenia (DIT) deserves a special focus since its cumulative incidence can be as high as 10 cases per million population per year, with a prevalence of approximately 25% in critically ill patients. This condition is usually suspected following identification of an acute and severe decrease in platelet count, with values usually < 50 ×109/L, thus potentially exposing patients to an increased risk of developing spontaneous hemorrhages. Conversely, however, some drug-related thrombocytopenias are instead (and perhaps counterintuitively) associated with increased thrombosis risk. Although a vast number of drugs have been implicated in DIT, the underlying pathogenetic mechanisms are essentially bifold, encompassing reduced platelet production due to bone marrow suppression (thus insufficient maturation or inefficient expansion of megakaryocytes, impaired release of platelets, or accelerated platelet apoptosis) or accelerated clearance of platelets from the circulation. This second form of DIT can be sustained by nonimmune, immune-mediated, or autoimmune mechanisms. An early and accurate diagnosis of DIT, which is crucial for reversing an otherwise unfavorable clinical outcome, is essentially based on the complete blood cell count, blood smear analysis, and performance of specific functional or immunochemical tests aimed at demonstrating the presence of antiplatelet antibodies.

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“…and their products (honey, royal jelly, venom, propolis, etc.) or biologically active substances derived from them as valuable resources to treat various diseases (Cherniack, 2010, 2011; Chen et al, 2018; Koh et al, 2018). Their properties range from immunomodulatory, analgesic, anti-bacterial, anti-coagulant, anticancer, diuretic and anesthetic to anti-rheumatic.…”

Section: Introductionmentioning

confidence: 99%

Deciphering Biological Processes at the Tick-Host Interface Opens New Strategies for Treatment of Human Diseases

et al. 2019

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Ticks are obligatory blood-feeding ectoparasites, causing blood loss and skin damage in their hosts. In addition, ticks also transmit a number of various pathogenic microorganisms that cause serious diseases in humans and animals. Ticks evolved a wide array of salivary bioactive compounds that, upon injection into the host skin, inhibit or modulate host reactions such as hemostasis, inflammation and wound healing. Modulation of the tick attachment site in the host skin involves mainly molecules which affect physiological processes orchestrated by cytokines, chemokines and growth factors. Suppressing host defense reactions is crucial for tick survival and reproduction. Furthermore, pharmacologically active compounds in tick saliva have a promising therapeutic potential for treatment of some human diseases connected with disorders in hemostasis and immune system. These disorders are often associated to alterations in signaling pathways and dysregulation or overexpression of specific cytokines which, in turn, affect mechanisms of angiogenesis, cell motility and cytoskeletal regulation. Moreover, tick salivary molecules were found to exert cytotoxic and cytolytic effects on various tumor cells and have anti-angiogenic properties. Elucidation of the mode of action of tick bioactive molecules on the regulation of cell processes in their mammalian hosts could provide new tools for understanding the complex changes leading to immune disorders and cancer. Tick bioactive molecules may also be exploited as new pharmacological inhibitors of the signaling pathways of cytokines and thus help alleviate patient discomfort and increase patient survival. We review the current knowledge about tick salivary peptides and proteins that have been identified and functionally characterized in in vitro and/or in vivo models and their therapeutic perspective.

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Toxins Are an Excellent Source of Therapeutic Agents against Cardiovascular Diseases

Cited by 18 publications

References 228 publications

Functional Mining of the Crotalus Spp. Venom Protease Repertoire Reveals Potential for Chronic Wound Therapeutics

Functional Mining of the Crotalus Spp. Venom Protease Repertoire Reveals Potential for Chronic Wound Therapeutics

Drug-Induced Thrombocytopenia: Mechanisms and Laboratory Diagnostics

Deciphering Biological Processes at the Tick-Host Interface Opens New Strategies for Treatment of Human Diseases

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