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Toxins
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Potential Therapeutic Applications of Animal Venoms and Toxins
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Potential Therapeutic Applications of Animal Venoms and Toxins

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 10117

Special Issue Editors

Prof. Dr. Márcia Mortari

E-Mail Website
Guest Editor
Laboratory of Neuropharmacology, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília, Brazil
Interests: venom; venom peptides; neuropeptides; neuropharmacology; neuroprotective peptides; antinociceptive peptides
Dr. Marlon Henrique Cardoso

E-Mail Website
Guest Editor
S-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco (UCDB), Campo Grande, MS, Brazil
Interests: peptide-based drug candidates; structure-guided design of antimicrobial peptides; peptidomimetics; molecular dynamics simulations of peptide-membrane, peptide-protein, protein-protein and membrane-receptor-peptide systems; nuclear magnetic resonance; bacterial resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Animal venoms are extraordinary tools for the study and development of new drugs. For millions of years, nature has provided the selection of more active and selective compounds capable of interacting with different pharmacological targets, empowering the venoms, and enabling them to perform numerous biological activities. Significantly, biotechnological research has provided advances in reducing limitations in the use of these compounds, presenting effective therapeutic applications, reducing adverse effects, and overcoming difficulties in relation to bioavailability and absorption. The use of compounds isolated from the venom and of new bioinspired molecules can strongly contribute to the treatment and study of diseases that so far have ineffective therapies, in addition to helping as an adjunct to existing therapies.

Prof. Dr. Márcia Mortari
Dr. Marlon Henrique Cardoso
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • animal venom studies
  • toxinology
  • peptides
  • therapeutic applications
  • biotechnological advances in toxinology

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Published Papers (4 papers)

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Research

16 pages, 2896 KiB  
Article
Crotoxin Modulates Macrophage Phenotypic Reprogramming
by Camila Lima Neves, Christiano Marcello Vaz Barbosa, Priscila Andrade Ranéia-Silva, Eliana L. Faquim-Mauro and Sandra Coccuzzo Sampaio
Toxins 2023, 15(10), 616; https://doi.org/10.3390/toxins15100616 - 17 Oct 2023
Viewed by 2161
Abstract
Macrophage plasticity is a fundamental feature of the immune response since it favors the rapid and adequate change of the functional phenotype in response to the pathogen or the microenvironment. Several studies have shown that Crotoxin (CTX), the major toxin of the Crotalus [...] Read more.
Macrophage plasticity is a fundamental feature of the immune response since it favors the rapid and adequate change of the functional phenotype in response to the pathogen or the microenvironment. Several studies have shown that Crotoxin (CTX), the major toxin of the Crotalus durissus terrificus snake venom, has a long-lasting antitumor effect both in experimental models and in clinical trials. In this study, we show the CTX effect on the phenotypic reprogramming of macrophages in the mesenchymal tumor microenvironment or those obtained from the peritoneal cavity of healthy animals. CTX (0.9 or 5 μg/animal subcutaneously) administered concomitantly with intraperitoneal inoculation of tumor cells (1 × 107/0.5 mL, injected intraperitoneally) of Ehrlich Ascitic Tumor (EAT) modulated the macrophages phenotype (M1), accompanied by increased NO• production by cells from ascites, and was evaluated after 13 days. On the other hand, in healthy animals, the phenotypic profile of macrophages was modulated in a dose-dependent way at 0.9 μg/animal: M1 and at 5.0 μg/animal: M2; this was accompanied by increased NO• production by peritoneal macrophages only for the dose of 0.9 μg/animal of CTX. This study shows that a single administration of CTX interferes with the phenotypic reprogramming of macrophages, as well as with the secretory state of cells from ascites, influencing events involved with mesenchymal tumor progression. These findings may favor the selection of new therapeutic targets to correct compromised immunity in different systems. Full article
(This article belongs to the Special Issue Potential Therapeutic Applications of Animal Venoms and Toxins)
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16 pages, 2621 KiB  
Article
A Metalloproteinase Cocktail from the Venom of Protobothrops flavoviridis Cleaves Amyloid Beta Peptides at the α-Cleavage Site
by Eugene Futai, Hajime Kawasaki, Shinichi Sato, Khadija Daoudi, Masafumi Hidaka, Taisuke Tomita and Tomohisa Ogawa
Toxins 2023, 15(8), 500; https://doi.org/10.3390/toxins15080500 - 12 Aug 2023
Cited by 2 | Viewed by 2894
Abstract
A disintegrin and metalloproteinase (ADAM) family proteins are a major class of membrane-anchored multidomain proteinases that are responsible for the shedding of cell surface protein ectodomains, including amyloid precursor protein (APP). Human ADAM 9, 10, and 17 proteolyze APPs and produce non-amyloid-genic p3 [...] Read more.
A disintegrin and metalloproteinase (ADAM) family proteins are a major class of membrane-anchored multidomain proteinases that are responsible for the shedding of cell surface protein ectodomains, including amyloid precursor protein (APP). Human ADAM 9, 10, and 17 proteolyze APPs and produce non-amyloid-genic p3 peptides, instead of neurotoxic amyloid-β peptides (Aβs; Aβ40 and Aβ42), which form fibrils and accumulate in the brain of patients with Alzheimer’s disease (AD). The ADAM family is closely related to snake venom metalloproteinases (SVMPs), which are derived from ancestral ADAMs but act as soluble proteinases. To test the therapeutic potential of SVMPs, we purified SVMPs from Protobothrops flavoviridis venom using metal ion affinity and pooled into a cocktail. Thus, 9 out of 11 SVMPs in the P. flavoviridis genome were identified in the cocktail. SVMPs inhibited Aβ secretion when added to human cell culture medium without affecting APP proteolysis. SVMPs degraded synthetic Aβ40 and Aβ42 peptides at the same cleavage site (α-site of APP) as ADAM9, 10, and 17. SVMPs did not degrade Aβ fibrils but interfered with their formation, assessed using thioflavin-T. Thus, SVMPs have therapeutic potential for AD as an Aβ-degrading protease, and the finding adds to the discovery of bioactive peptides from venoms as novel therapeutics. Full article
(This article belongs to the Special Issue Potential Therapeutic Applications of Animal Venoms and Toxins)
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18 pages, 3094 KiB  
Article
Cancer Wars: Revenge of the AMPs (Antimicrobial Peptides), a New Strategy against Colorectal Cancer
by Mina Răileanu and Mihaela Bacalum
Toxins 2023, 15(7), 459; https://doi.org/10.3390/toxins15070459 - 14 Jul 2023
Cited by 6 | Viewed by 2207
Abstract
Cancer is a multifaceted health issue that affects people globally and it is considered one of the leading causes of death with a high percentage of victims worldwide. In recent years, research studies have uncovered great advances in cancer diagnosis and treatment. But, [...] Read more.
Cancer is a multifaceted health issue that affects people globally and it is considered one of the leading causes of death with a high percentage of victims worldwide. In recent years, research studies have uncovered great advances in cancer diagnosis and treatment. But, there are still major drawbacks of the conventional therapies used including severe side effects, toxicity, and drug resistance. That is why it is critical to develop new drugs with advantages like low cytotoxicity and no treatment resistance to the cancer cells. Antimicrobial peptides (AMPs) have recently attracted attention as a novel therapeutic strategy for the treatment of various cancers, targeting tumor cells with less toxicity to normal tissues. The aim of the study was to discover alternate treatments that do not lead to cancer resistance and have fewer side effects. Here, we report the effects induced by several AMPs, Melittin, Cecropin A, and a Cecropin A—Melittin hybrid, against two human colorectal cancer-derived spheroids. To study the effects of the peptides, cell viability was investigated using MTT, LDH, and ATP assays. Furthermore, cellular senescence and cell cycle were investigated. We found that using different concentrations of these peptides affected the spheroids, their structure being highly compromised by reducing cell viability, and the increase in ATP and LDH levels. Also, the cells are arrested in the G2/M phase leading to an increase in senescent cells. We show that Melittin and the hybrid are most effective against the 3D colorectal cancer cells compared to Cecropin A. Full article
(This article belongs to the Special Issue Potential Therapeutic Applications of Animal Venoms and Toxins)
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15 pages, 2470 KiB  
Article
Natriuretic-like Peptide Lebetin 2 Mediates M2 Macrophage Polarization in LPS-Activated RAW264.7 Cells in an IL-10-Dependent Manner
by Dorsaf Bouzazi, Wael Mami, Amor Mosbah, Naziha Marrakchi, Melika Ben Ahmed and Erij Messadi
Toxins 2023, 15(4), 298; https://doi.org/10.3390/toxins15040298 - 19 Apr 2023
Cited by 3 | Viewed by 2340
Abstract
Snake natriuretic peptide (NP) Lebetin 2 (L2) has been shown to improve cardiac function and reduce fibrosis as well as inflammation by promoting M2-type macrophages in a reperfused myocardial infarction (MI) model. However, the inflammatory mechanism of L2 remains unclear. Therefore, we investigated [...] Read more.
Snake natriuretic peptide (NP) Lebetin 2 (L2) has been shown to improve cardiac function and reduce fibrosis as well as inflammation by promoting M2-type macrophages in a reperfused myocardial infarction (MI) model. However, the inflammatory mechanism of L2 remains unclear. Therefore, we investigated the effect of L2 on macrophage polarization in lipopolysaccharide (LPS)-activated RAW264.7 cells in vitro and explored the associated underlying mechanisms. TNF-α, IL-6 and IL-10 levels were assessed using an ELISA assay, and M2 macrophage polarization was determined by flow cytometry. L2 was used at non-cytotoxic concentrations determined by a preliminary MTT cell viability assay, and compared to B-type natriuretic peptide (BNP). In LPS-activated cells, both peptides reduced TNF-α and IL-6 release compared to controls. However, only L2 increased IL-10 release in a sustained manner and promoted downstream M2 macrophage polarization. Pretreatment of LPS-activated RAW264.7 cells with the selective NP receptor (NPR) antagonist isatin abolished both IL-10 and M2-like macrophage potentiation provided by L2. In addition, cell pretreatment with the IL-10 inhibitor suppressed L2-induced M2 macrophage polarization. We conclude that L2 exerts an anti-inflammatory response to LPS by regulating the release of inflammatory cytokines via stimulating of NP receptors and promoting M2 macrophage polarization through activation of IL-10 signaling. Full article
(This article belongs to the Special Issue Potential Therapeutic Applications of Animal Venoms and Toxins)
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