Special Issue "Drug Development Using Natural Toxins"

A special issue of Toxins (ISSN 2072-6651).

Deadline for manuscript submissions: closed (31 December 2020).

Special Issue Editor

Prof. Dr. Gihyun Lee
E-Mail Website
Guest Editor
College of Korean Medicine, Dongshin University, Naju 58245, Korea
Interests: venom; drug discovery; pharmacology; herbal medicine; immune response
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Natural toxins are poisonous substances produced by bacteria, insects, animals, or plants. They cause pain, disease, and even death to victims, but they also provide humans with a rich resource for new drugs for a variety of targets, from pain to lethal diseases.

Toxins have long been used to treat diseases globally, but they have not been studied enough as a drug candidate. Bee venom, one of the most widely used toxins used for therapeutic purposes, still applies to efficacy and safety as a remedy for many diseases. It is at the beginning stage of drug development studies, with other poisons such as those from snake, scorpion, and toad venoms. Toxic medicinal plants, which have been used in traditional medicine for a long time, are highly valuable in drug development as well as in treating various diseases.

This Special Issue aims to provide a comprehensive view of natural toxins having therapeutic potential. We hope that researchers will share their valuable studies using natural toxins for drug development.

Prof. Dr. Gihyun Lee
Guest Editor

Manuscript Submission Information

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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 2400 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

  • toxin
  • venom
  • drug development
  • therapeutic application
  • medicine

Published Papers (13 papers)

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Editorial

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Editorial
Drug Development Using Natural Toxins
Toxins 2021, 13(6), 414; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13060414 - 11 Jun 2021
Viewed by 749
Abstract
Natural toxins are poisonous substances produced by bacteria, insects, animals, or plants [...] Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)

Research

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Article
In Vitro and In Vivo Antibacterial Activity of Gliotoxin Alone and in Combination with Antibiotics against Staphylococcus aureus
Toxins 2021, 13(2), 85; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020085 - 23 Jan 2021
Cited by 1 | Viewed by 676
Abstract
Multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of hospital-acquired and community infections and pose a challenge to the human health care system. Therefore, it is important to find new drugs that show activity against these bacteria, [...] Read more.
Multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of hospital-acquired and community infections and pose a challenge to the human health care system. Therefore, it is important to find new drugs that show activity against these bacteria, both in monotherapy and in combination with other antimicrobial drugs. Gliotoxin (GT) is a mycotoxin produced by Aspergillus fumigatus and other fungi of the Aspergillus genus. Some evidence suggests that GT shows antimicrobial activity against S. aureus in vitro, albeit its efficacy against multidrug-resistant strains such as MRSA or vancomycin-intermediate S. aureus (VISA) strainsis not known. This work aimed to evaluate the antibiotic efficacy of GT as monotherapy or in combination with other therapeutics against MRSA in vitro and in vivo using a Caenorhabditis elegans infection model. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
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Article
Venom of the Red-Bellied Black Snake Pseudechis porphyriacus Shows Immunosuppressive Potential
Toxins 2020, 12(11), 674; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12110674 - 26 Oct 2020
Cited by 3 | Viewed by 1271
Abstract
Venoms act with remarkable specificity upon a broad diversity of physiological targets. Venoms are composed of proteins, peptides, and small molecules, providing the foundation for the development of novel therapeutics. This study assessed the effect of venom from the red-bellied black snake ( [...] Read more.
Venoms act with remarkable specificity upon a broad diversity of physiological targets. Venoms are composed of proteins, peptides, and small molecules, providing the foundation for the development of novel therapeutics. This study assessed the effect of venom from the red-bellied black snake (Pseudechis porphyriacus) on human primary leukocytes using bead-based flow cytometry, mixed lymphocyte reaction, and cell viability assays. We show that venom treatment had a significant immunosuppressive effect, inhibiting the secretion of interleukin (IL)-2 and tumor necrosis factor (TNF) from purified human T cells by 90% or greater following stimulation with mitogen (phorbol 12-myristate 13-acetate and ionomycin) or via cluster of differentiation (CD) receptors, CD3/CD28. In contrast, venom treatment did not inhibit TNF or IL-6 release from antigen-presenting cells stimulated with lipopolysaccharide. The reduced cytokine release from T cells was not associated with inhibition of T cell proliferation or reduction of cell viability, consistent with an anti-inflammatory mechanism unrelated to the cell cycle. Deconvolution of the venom using reverse-phase HPLC identified four fractions responsible for the observed immunosuppressive activity. These data suggest that compounds from P. porphyriacus venom may be potential drug leads for T cell-associated conditions such as graft versus host disease, rheumatoid arthritis, and inflammatory bowel disease. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
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Communication
Evaluation of Antifungal Activity of Naja pallida and Naja mossambica Venoms against Three Candida Species
Toxins 2020, 12(8), 500; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12080500 - 04 Aug 2020
Cited by 3 | Viewed by 1148
Abstract
In contrast to comprehensively investigated antibacterial activity of snake venoms, namely crude venoms and their selected components, little is known about antifungal properties of elapid snake venoms. In the present study, the proteome of two venoms of red spitting cobra Naja pallida (NPV) [...] Read more.
In contrast to comprehensively investigated antibacterial activity of snake venoms, namely crude venoms and their selected components, little is known about antifungal properties of elapid snake venoms. In the present study, the proteome of two venoms of red spitting cobra Naja pallida (NPV) and Mozambique spitting cobra Naja mossambica (NMV) was characterized using LC-MS/MS approach, and the antifungal activity of crude venoms against three Candida species was established. A complex response to venom treatment was revealed. NPV and NMV, when used at relatively high concentrations, decreased cell viability of C. albicans and C. tropicalis, affected cell cycle of C. albicans, inhibited C. tropicalis-based biofilm formation and promoted oxidative stress in C. albicans, C. glabrata and C. tropicalis cells. NPV and NMV also modulated ammonia pulses during colony development and aging in three Candida species. All these observations provide evidence that NPV and NMV may diminish selected pathogenic features of Candida species. However, NPV and NMV also promoted the secretion of extracellular phospholipases that may facilitate Candida pathogenicity and limit their usefulness as anti-candidal agents. In conclusion, antifungal activity of snake venoms should be studied with great caution and a plethora of pathogenic biomarkers should be considered in the future experiments. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
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Article
Enhanced Antimicrobial Activity of N-Terminal Derivatives of a Novel Brevinin-1 Peptide from The Skin Secretion of Odorrana schmackeri
Toxins 2020, 12(8), 484; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12080484 - 30 Jul 2020
Cited by 3 | Viewed by 1153
Abstract
Antimicrobial peptides (AMPs) are promising therapeutic alternatives compared to conventional antibiotics for the treatment of drug-resistant bacterial infections. However, the application of the overwhelming majority of AMPs is limited because of the high toxicity and high manufacturing costs. Amphibian skin secretion has been [...] Read more.
Antimicrobial peptides (AMPs) are promising therapeutic alternatives compared to conventional antibiotics for the treatment of drug-resistant bacterial infections. However, the application of the overwhelming majority of AMPs is limited because of the high toxicity and high manufacturing costs. Amphibian skin secretion has been proven to be a promising source for the discovery and development of novel AMPs. Herein, we discovered a novel AMP from the skin secretion of Odorrana schmackeri, and designed the analogues by altering the key factors, including conformation, net charge and amphipathicity, to generate short AMPs with enhanced therapeutic efficacy. All the peptides were chemically synthesised, followed by evaluating their biological activity, stability and cytotoxicity. OSd, OSe and OSf exhibited broad-spectrum antibacterial effects, especially OSf, which presented the highest therapeutic index for the tested bacteria. Moreover, these peptides displayed good stability. The results from scanning electron microscopy and transmission electron microscopy studies, indicated that brevinin-OS, OSd, OSe and OSf possessed rapid bactericidal ability by disturbing membrane permeability and causing the release of cytoplasmic contents. In addition, OSd, OSe and OSf dramatically decreased the mortality of waxworms acutely infected with MRSA. Taken together, these data suggested that a balance between positive charge, degrees of α-helicity and hydrophobicity, is necessary for maintaining antimicrobial activity, and these data successfully contributed to the design of short AMPs with significant bactericidal activity and cell selectivity. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
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Article
Potential of Bacteriocins from Lactobacillus taiwanensis for Producing Bacterial Ghosts as a Next Generation Vaccine
Toxins 2020, 12(7), 432; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12070432 - 01 Jul 2020
Cited by 8 | Viewed by 966
Abstract
Bacteriocins are functionally diverse toxins produced by most microbes and are potent antimicrobial peptides (AMPs) for bacterial ghosts as next generation vaccines. Here, we first report that the AMPs secreted from Lactobacillus taiwanensis effectively form ghosts of pathogenic bacteria and are identified as [...] Read more.
Bacteriocins are functionally diverse toxins produced by most microbes and are potent antimicrobial peptides (AMPs) for bacterial ghosts as next generation vaccines. Here, we first report that the AMPs secreted from Lactobacillus taiwanensis effectively form ghosts of pathogenic bacteria and are identified as diverse bacteriocins, including novel ones. In detail, a cell-free supernatant from L. taiwanensis exhibited antimicrobial activities against pathogenic bacteria and was observed to effectively cause cellular lysis through pore formation in the bacterial membrane using scanning electron microscopy (SEM). The treatment of the cell-free supernatant with proteinase K or EDTA proved that the antimicrobial activity is mediated by AMPs, and the purification of AMPs using Sep-Pak columns indicated that the cell-free supernatant includes various amphipathic peptides responsible for the antimicrobial activity. Furthermore, the whole-genome sequencing of L. taiwanensis revealed that the strain has diverse bacteriocins, confirmed experimentally to function as AMPs, and among them are three novel bacteriocins, designated as Tan 1, Tan 2, and Tan 3. We also confirmed, using SEM, that Tan 2 effectively produces bacterial ghosts. Therefore, our data suggest that the bacteriocins from L. taiwanensis are potentially useful as a critical component for the preparation of bacterial ghosts. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
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Communication
Ephedra sinica Stapf and Gypsum Attenuates Heat-Induced Hypothalamic Inflammation in Mice
Toxins 2020, 12(1), 16; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12010016 - 30 Dec 2019
Cited by 5 | Viewed by 1220
Abstract
Ephedra sinica Stapf (EH) exert toxic effects, such as excitability, cardiac arrhythmia, and others. On the contrary, in traditional herbal medicine, EH and gypsum (GF) are used most often to treat symptoms caused by external stressors. The hypothalamus plays a crucial role in [...] Read more.
Ephedra sinica Stapf (EH) exert toxic effects, such as excitability, cardiac arrhythmia, and others. On the contrary, in traditional herbal medicine, EH and gypsum (GF) are used most often to treat symptoms caused by external stressors. The hypothalamus plays a crucial role in thermal homeostasis. Inflammatory response in the hypothalamus by thermal stressors may affect thermal and energy homeostasis. This study investigates the effect of EH and GF against heat-induced mouse model. Mice were divided into four groups: saline, saline plus heat, EH plus heat, and GF plus heat treated groups. Heat stress was fixed at 43 °C for 15 min once daily for 3 days. Weight and ear and rectal temperature measurements were made after terminating heat stress. Hypothalamus tissue was collected to evaluate the HSP70, nuclear factor kappa-Β (NF-kB), and interleukin (IL)-1β protein expression levels. EH and GF treatment suppressed the increased body temperature. EH significantly ameliorated heat-induced body weight loss, compared to gypsum. Regulatory effects of EH and GF for body temperature and weight against heat stress were mediated by IL-1β reduction. EH showed significant HSP70 and NF-kB inhibition against heat stress. EH and GF contribute to the inhibition of heat-induced proinflammatory factors and the promotion of hypothalamic homeostasis. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
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Review

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Review
Bee Venom Components as Therapeutic Tools against Prostate Cancer
Toxins 2021, 13(5), 337; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13050337 - 07 May 2021
Cited by 1 | Viewed by 883
Abstract
Prostate cancer is one of the most common cancers in men. Despite the development of a variety of therapeutic agents to treat either metastatic hormone-sensitive prostate cancer, advanced prostate cancer, or nonmetastatic/metastatic castration-resistant prostate cancer, the progression or spread of the disease often [...] Read more.
Prostate cancer is one of the most common cancers in men. Despite the development of a variety of therapeutic agents to treat either metastatic hormone-sensitive prostate cancer, advanced prostate cancer, or nonmetastatic/metastatic castration-resistant prostate cancer, the progression or spread of the disease often cannot be avoided. Additionally, the development of resistance of prostate cancer cells to available therapeutic agents is a well-known problem. Despite extensive and cost-intensive research over decades, curative therapy for metastatic prostate cancer is still not available. Therefore, additional therapeutic agents are still needed. The animal kingdom offers a valuable source of natural substances used for the treatment of a variety of diseases. Bee venom of the honeybee is a mixture of many components. It contains proteins acting as enzymes such as phospholipase A2, smaller proteins and peptides such as melittin and apamin, phospholipids, and physiologically active amines such as histamine, dopamine, and noradrenaline. Melittin has been shown to induce apoptosis in different cancer cell lines, including prostate cancer cell lines. It also influences cell proliferation, angiogenesis, and necrosis as well as motility, migration, metastasis, and invasion of tumour cells. Hence, it represents an interesting anticancer agent. In this review article, studies about the effect of bee venom components on prostate cancer cells are discussed. An electronic literature research was performed utilising PubMed in February 2021. All scientific publications, which examine this interesting subject, are discussed. Furthermore, the different types of application of these promising substances are outlined. The studies clearly indicate that bee venom or melittin exhibited anticancer effects in various prostate cancer cell lines and in xenografts. In most of the studies, a combination of bee venom or the modified melittin with another molecule was utilised in order to avoid side effects and, additionally, to target selectively the prostate cancer cells or the surrounding tissue. The studies showed that systemic side effects and unwanted damage to healthy tissue and organs could be minimised when the anticancer drug was not activated until binding to the cancer cells or the surrounding tissue. Different targets were used, such as the matrix metalloproteinase 2, hormone receptors expressed by prostate cancer cells, the extracellular domain of PSMA, and the fibroblast activation protein occurring in the stroma of prostate cancer cells. Another approach used loaded phosphate micelles, which were cleaved by the enzyme secretory phospholipase A2 produced by prostate cancer cells. In a totally different approach, targeted nanoparticles containing the melittin gene were used for prostate cancer gene therapy. By the targeted nonviral gene delivery, the gene encoding melittin was delivered to the prostate cancer cells without systemic side effects. This review of the scientific literature reveals totally different approaches using bee venom, melittin, modified melittin, or protoxin as anticancer agents. The toxic agents acted through several different mechanisms to produce their anti-prostate cancer effects. These mechanisms are not fully understood yet and more experimental studies are necessary to reveal the complete mode of action. Nevertheless, the researchers have conducted pioneering work. Based on these results, further experimental and clinical studies about melittin and modifications of this interesting agent deriving from nature are necessary and could possibly lead to a complementary treatment option for prostate cancer. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
Review
Toxic Animal-Based Medicinal Materials Can Be Effective in Treating Endometriosis: A Scoping Review
Toxins 2021, 13(2), 145; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020145 - 14 Feb 2021
Cited by 1 | Viewed by 666
Abstract
Animal toxins and venoms have recently been developed as cancer treatments possessing tumor cell growth-inhibitory, antiangiogenesis, and proapoptotic effects. Endometriosis is a common benign gynecological disorder in reproductive-age women, and no definite treatment for this disorder is without severe side effects. As endometriosis [...] Read more.
Animal toxins and venoms have recently been developed as cancer treatments possessing tumor cell growth-inhibitory, antiangiogenesis, and proapoptotic effects. Endometriosis is a common benign gynecological disorder in reproductive-age women, and no definite treatment for this disorder is without severe side effects. As endometriosis and malignant tumors share similar characteristics (progressive, invasive, estrogen-dependent growth, and recurrence), animal toxins and venoms are thought to be effective against endometriosis. The objective of this study was to outline studies using toxic animal-based medicinal materials (TMM) as endometriosis treatment and to explore its clinical applicability. Preclinical and clinical studies using TMM were searched for in four databases from inception to October 2020. A total of 20 studies of TMM on endometriosis were included. In eight clinical studies, herbal medicines containing TMM were effective in relieving symptoms of endometriosis, with no side effects. In twelve experimental studies, the main therapeutic mechanisms of TMM against endometriosis were proapoptotic, antiangiogenesis, estrogen level-reducing, and possible anti-inflammatory effects. TMM are thus considered promising sources for the development of an effective treatment method for endometriosis. Further studies are needed to clarify the therapeutic mechanism of TMM against endometriosis and to provide sufficient grounds for clinical application. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
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Review
Animal Venom for Medical Usage in Pharmacopuncture in Korean Medicine: Current Status and Clinical Implication
Toxins 2021, 13(2), 105; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020105 - 01 Feb 2021
Cited by 2 | Viewed by 704
Abstract
Animal venoms, widespread throughout the world, are complex mixtures, the composition of which depends on the venom-producing species. The objective of this study was to contribute to the development of animal venom-based medicines by investigating the use of animal venom pharmacopuncture in Korean [...] Read more.
Animal venoms, widespread throughout the world, are complex mixtures, the composition of which depends on the venom-producing species. The objective of this study was to contribute to the development of animal venom-based medicines by investigating the use of animal venom pharmacopuncture in Korean medicine (KM) institutions. We surveyed 256 public health centers from 1 through 31 October 2019 as guided by the Ministry of Health and Welfare (MoHW). A questionnaire developed by an expert group was distributed and collected for statistical analysis. The survey identified three types of animal venom-based pharmacopuncture: bee, snake, and toad venoms. The medications are based on a single animal venom ingredient and produced in 11 external herbal dispensaries (EHDs). Each animal venom is processed, refined, and freeze-dried in a cleanroom to produce a powder formulation that is later measured, diluted, filtered, filled, sealed, sterilized, and packaged as pharmacopuncture injections used in KM institutions. Bee venom therapy is effective in treating musculoskeletal pain, snake venom therapy is effective in controlling bleeding during surgery, and toad venom therapy is effective in cancer treatment. The study suggests that bee, snake, and toad venoms could be used in medical institutions and have the potential for drug development. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
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Review
Clinical Effectiveness and Adverse Events of Bee Venom Therapy: A Systematic Review of Randomized Controlled Trials
Toxins 2020, 12(9), 558; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12090558 - 29 Aug 2020
Cited by 4 | Viewed by 1553
Abstract
Bee venom has been used to treat many diseases because of its anti-inflammatory and analgesic effects. However, the secretions of bee venom can also cause life-threatening adverse reactions. The objective of this paper was to review the clinical effectiveness of bee venom and [...] Read more.
Bee venom has been used to treat many diseases because of its anti-inflammatory and analgesic effects. However, the secretions of bee venom can also cause life-threatening adverse reactions. The objective of this paper was to review the clinical effectiveness of bee venom and adverse events induced by bee venom, regardless of the disease. Four electronic databases were searched in April 2020. The reference lists of the retrieved articles and previous review articles were also hand-searched. Randomized controlled trials (RCTs) using any type of bee venom other than live bee stings for the clinical treatment of any disease other than cancer were included. The studies were selected, the data were extracted, and the quality of the studies was assessed by two authors. Risk of bias was assessed using the Cochrane risk of bias standards. Twelve RCTs were included in this review—three on Parkinson’s disease, four on arthralgia, four on musculoskeletal disorders, and one on polycystic ovary syndrome. The types of bee venom used were acupuncture injections, ultrasound gel, and an ointment. Six studies reported adverse events, and skin reactions such as pruritus and swelling were the most common. The large-scale clinical trials of bee venom therapy are needed to verify the statistical difference, and the reporting system for adverse events is also required to increase the safety of bee venom therapy. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
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Review
Over 25 Years of Pediatric Botulinum Toxin Treatments: What Have We Learned from Injection Techniques, Doses, Dilutions, and Recovery of Repeated Injections?
Toxins 2020, 12(7), 440; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12070440 - 06 Jul 2020
Cited by 6 | Viewed by 1356
Abstract
Botulinum toxin type A (BTXA) has been used for over 25 years in the management of pediatric lower and upper limb hypertonia, with the first reports in 1993. The most common indication is the injection of the triceps surae muscle for the correction [...] Read more.
Botulinum toxin type A (BTXA) has been used for over 25 years in the management of pediatric lower and upper limb hypertonia, with the first reports in 1993. The most common indication is the injection of the triceps surae muscle for the correction of spastic equinus gait in children with cerebral palsy. The upper limb injection goals include improvements in function, better positioning of the arm, and facilitating the ease of care. Neurotoxin type A is the most widely used serotype in the pediatric population. After being injected into muscle, the release of acetylcholine at cholinergic nerve endings is blocked, and a temporary denervation and atrophy ensues. Targeting the correct muscle close to the neuromuscular junctions is considered essential and localization techniques have developed over time. However, each technique has its own limitations. The role of BTXA is flexible, but limited by the temporary mode of action as a focal spasticity treatment and the restrictions on the total dose deliverable per visit. As a mode of treatment, repeated BTXA injections are needed. This literature reviewed BTXA injection techniques, doses and dilutions, the recovery of muscles and the impact of repeated injections, with a focus on the pediatric population. Suggestions for future studies are also discussed. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
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Review
Forty Years of the Description of Brown Spider Venom Phospholipases-D
Toxins 2020, 12(3), 164; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12030164 - 06 Mar 2020
Cited by 8 | Viewed by 1272
Abstract
Spiders of the genus Loxosceles, popularly known as Brown spiders, are considered a serious public health issue, especially in regions of hot or temperate climates, such as parts of North and South America. Although the venoms of these arachnids are complex in [...] Read more.
Spiders of the genus Loxosceles, popularly known as Brown spiders, are considered a serious public health issue, especially in regions of hot or temperate climates, such as parts of North and South America. Although the venoms of these arachnids are complex in molecular composition, often containing proteins with distinct biochemical characteristics, the literature has primarily described a family of toxins, the Phospholipases-D (PLDs), which are highly conserved in all Loxosceles species. PLDs trigger most of the major clinical symptoms of loxoscelism i.e., dermonecrosis, thrombocytopenia, hemolysis, and acute renal failure. The key role played by PLDs in the symptomatology of loxoscelism was first described 40 years ago, when researches purified a hemolytic toxin that cleaved sphingomyelin and generated choline, and was referred to as a Sphingomyelinase-D, which was subsequently changed to Phospholipase-D when it was demonstrated that the enzyme also cleaved other cellular phospholipids. In this review, we present the information gleaned over the last 40 years about PLDs from Loxosceles venoms especially with regard to the production and characterization of recombinant isoforms. The history of obtaining these toxins is discussed, as well as their molecular organization and mechanisms of interaction with their substrates. We will address cellular biology aspects of these toxins and how they can be used in the development of drugs to address inflammatory processes and loxoscelism. Present and future aspects of loxoscelism diagnosis will be discussed, as well as their biotechnological applications and actions expected for the future in this field. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
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