RESUMEN
Snakebite envenomation (SBE)-induced immunity refers to individuals who have been previously bitten by a snake and developed a protective immune response against subsequent envenomations. The notion stems from observations of individuals, including in the indigenous population, who present only mild signs and symptoms after surviving multiple SBEs. Indeed, these observations have engendered scientific interest and prompted inquiries into the potential development of a protective immunity from exposure to snake toxins. This review explores the evidence of a protective immune response developing following SBE. Studies suggest that natural exposure to snake toxins can trigger protection from the severity of SBEs, mediated by specific antibodies. However, the evaluation of the immune memory response in SBE patients remains challenging. Further research is needed to elucidate the immune response dynamics and identify potential targets for therapeutic interventions. Furthermore, the estimation of the effect of previous exposures on SBE epidemiology in hyperendemic areas, such as in the indigenous villages of the Amazon region (e.g., the Yanomami population) is a matter of debate.
Asunto(s)
Mordeduras de Serpientes , Toxinas Biológicas , Animales , Humanos , Mordeduras de Serpientes/tratamiento farmacológico , Antivenenos/uso terapéutico , Serpientes , Toxinas Biológicas/uso terapéutico , Venenos de Serpiente/uso terapéuticoRESUMEN
Malaria is an infectious disease caused by Plasmodium spp. and it is mainly transmitted to humans by female mosquitoes of the genus Anopheles. Malaria is an important global public health problem due to its high rates of morbidity and mortality. At present, drug therapies and vector control with insecticides are respectively the most commonly used methods for the treatment and control of malaria. However, several studies have shown the resistance of Plasmodium to drugs that are recommended for the treatment of malaria. In view of this, it is necessary to carry out studies to discover new antimalarial molecules as lead compounds for the development of new medicines. In this sense, in the last few decades, animal venoms have attracted attention as a potential source for new antimalarial molecules. Therefore, the aim of this review was to summarize animal venom toxins with antimalarial activity found in the literature. From this research, 50 isolated substances, 4 venom fractions and 7 venom extracts from animals such as anurans, spiders, scorpions, snakes, and bees were identified. These toxins act as inhibitors at different key points in the biological cycle of Plasmodium and may be important in the context of the resistance of Plasmodium to currently available antimalarial drugs.
Asunto(s)
Anopheles , Antimaláricos , Malaria , Plasmodium , Toxinas Biológicas , Femenino , Humanos , Animales , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Ponzoñas/farmacología , Ponzoñas/uso terapéutico , Mosquitos Vectores , Malaria/tratamiento farmacológico , Toxinas Biológicas/uso terapéutico , Plasmodium falciparumRESUMEN
Breast cancer is one of the most common cancers in women worldwide. Conventional cancer chemotherapy always has adverse side effects on the patient's healthy tissues. Consequently, combining pore-forming toxins with cell-targeting peptides (CTPs) is a promising anticancer strategy for selectively destroying cancer cells. Here, we aim to improve the target specificity of the BinB toxin produced from Lysinibacillus sphaericus (Ls) by fusing a luteinizing hormone-releasing hormone (LHRH) peptide to its pore-forming domain (BinBC) to target MCF-7 breast cancer cells as opposed to human fibroblast cells (Hs68). The results showed that LHRH-BinBC inhibited MCF-7 cell proliferation in a dose-dependent manner while leaving Hs68 cells unaffected. BinBC, at any concentration tested, did not affect the proliferation of MCF-7 or Hs68 cells. In addition, the LHRH-BinBC toxin caused the efflux of the cytoplasmic enzyme lactate dehydrogenase (LDH), demonstrating the efficacy of the LHRH peptide in directing the BinBC toxin to damage the plasma membranes of MCF-7 cancer cells. LHRH-BinBC also caused MCF-7 cell apoptosis by activating caspase-8. In addition, LHRH-BinBC was predominantly observed on the cell surface of MCF-7 and Hs68 cells, without colocalization with mitochondria. Overall, our findings suggest that LHRH-BinBC could be investigated further as a potential cancer therapeutic agent.
Asunto(s)
Neoplasias de la Mama , Toxinas Biológicas , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Hormona Liberadora de Gonadotropina , Toxinas Biológicas/uso terapéutico , Membrana Celular/metabolismo , Células MCF-7RESUMEN
Protein-bound uremic toxins, mainly indoxyl sulfate (3-INDS), p-cresol sulfate (pCS), and indole-3-acetic acid (3-IAA) but also phenol (Pol) and p-cresol (pC), are progressively accumulated during chronic kidney disease (CKD). Their accurate measurement in biomatrices is demanded for timely diagnosis and adoption of appropriate therapeutic measures. Multianalyte methods allowing the establishment of a uremic metabolite profile are still missing. Hence, the aim of this work was to develop a rapid and sensitive method based on high-performance liquid chromatography with fluorescence detection for the simultaneous quantification of Pol, 3-IAA, pC, 3-INDS, and pCS in human plasma. Separation was attained in 12 min, using a monolithic C18 column and isocratic elution with acetonitrile and phosphate buffer containing an ion-pairing reagent, at a flow rate of 2 mL min-1. Standards were prepared in plasma and quantification was performed using the background subtraction approach. LOQ values were ≤ 0.2 µg mL-1 for all analytes except for pCS (LOQ of 2 µg mL-1). The method proved to be accurate (93.5-112%) and precise (CV ≤ 14.3%). The multianalyte application of the method, associated to a reduced sample volume (50 µL), a less toxic internal standard (eugenol) in comparison to the previously applied 2,6-dimethylphenol and 4-ethylphenol, and a green extraction solvent (ethanol), resulted in the AGREE score of 0.62 which is in line with the recent trend of green and sustainable analytical chemistry. The validated method was successfully applied to the analysis of plasma samples from control subjects exhibiting normal levels of uremic toxins and CKD patients presenting significantly higher levels of 3-IAA, pC, 3-INDS, and pCS that can be further investigated as biomarkers of disease progression.
Asunto(s)
Insuficiencia Renal Crónica , Toxinas Biológicas , Humanos , Tóxinas Urémicas , Cromatografía Líquida de Alta Presión/métodos , Cresoles/metabolismo , Cresoles/uso terapéutico , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/metabolismo , Fenol , Indicán/química , Indicán/metabolismo , Toxinas Biológicas/metabolismo , Toxinas Biológicas/uso terapéuticoRESUMEN
Crocodile tear syndrome (CTS) is a late complication of facial nerve palsy characterized by unilateral lacrimation in response to gustatory stimulation. We present 2 cases of patients diagnosed with CTS after recovering from unilateral idiopathic facial nerve palsy. Both patients underwent transconjunctival lacrimal gland incobotulinumtoxinA injection, with doses of 5-16 units. The patients were seen in clinic for post-treatment follow-up at 2 weeks, 3 months, and 6 months. Outcomes were measured by treatment efficacy and adverse drug effects. Following treatment, both patients reported resolution of gustatory lacrimation. The patient treated with 16 U experienced transient ptosis and diplopia following injection, whereas the patient treated with 5-7.5 U experienced no adverse effects.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo , Parálisis de Bell , Blefaroptosis , Toxinas Botulínicas Tipo A , Trastornos Congénitos de Denervación Craneal , Parálisis Facial , Anomalías Maxilomandibulares , Enfermedades del Aparato Lagrimal , Aparato Lagrimal , Fármacos Neuromusculares , Reflejo Anormal , Toxinas Biológicas , Humanos , Aparato Lagrimal/inervación , Toxinas Botulínicas Tipo A/farmacología , Toxinas Botulínicas Tipo A/uso terapéutico , Fármacos Neuromusculares/farmacología , Fármacos Neuromusculares/uso terapéutico , Enfermedades del Aparato Lagrimal/diagnóstico , Enfermedades del Aparato Lagrimal/tratamiento farmacológico , Parálisis Facial/complicaciones , Parálisis Facial/tratamiento farmacológico , Parálisis de Bell/complicaciones , Parálisis de Bell/tratamiento farmacológico , Enfermedades del Sistema Nervioso Autónomo/complicaciones , Enfermedades del Sistema Nervioso Autónomo/tratamiento farmacológico , Toxinas Biológicas/farmacología , Toxinas Biológicas/uso terapéuticoRESUMEN
The French Society of Toxinology (SFET) organized its 27th annual meeting on 9-10 December 2021 as a virtual meeting (e-RT27). The central theme of this meeting was "Toxins: Mr Hyde or Dr Jekyll?", emphasizing the latest findings on plant, fungal, algal, animal and bacterial toxins during 10 lectures, 15 oral communications (shorter lectures) and 20 posters shared by ca. 80 participants. The abstracts of lectures and posters, as well as the winners of the best oral communication and poster awards, are presented in this report.
Asunto(s)
Toxinas Biológicas , Animales , Distinciones y Premios , Humanos , Sociedades Científicas , Toxinas Biológicas/farmacología , Toxinas Biológicas/uso terapéutico , Toxinas Biológicas/toxicidadRESUMEN
Under continuous long-term treatment with abo- or onabotulinum toxin type A (BoNT/A), ~10 to 15% of patients with cervical dystonia (CD) will develop neutralizing antibodies and reduced responsiveness over an ~10-year treatment period. Among the botulinum neurotoxin type A preparations so far licensed for CD, incobotulinum toxin A (incoBoNT/A; Xeomin®) is the only one without complex proteins. Whether CD patients with treatment failure under abo- or onaBoNT/A may still respond to incoBoNT/A is unknown. In this cross-sectional, retrospective study, 64 CD patients with secondary treatment failure after abo- or onaBoNT/A therapy who were switched to incoBoNT/A were compared to 34 CD patients exclusively treated with incoBoNT/A. The initial clinical severity of CD, best outcome during abo- or onaBoNT/A therapy, severity at the time of switching to incoBoNT/A and severity at recruitment, as well as all corresponding doses, were analyzed. Furthermore, the impact of neutralizing antibodies (NABs) on the long-term outcome of incoBoNT/A therapy was evaluated. Patients significantly improved after the switch to incoBoNT/A (p < 0.001) but did not reach the improvement level obtained before the development of partial secondary treatment failure or that of patients who were exclusively treated with incoBoNT/A. No difference between abo- and onaBoNT/A pretreatments or between the long-term outcomes of NAB-positive and NAB-negative patients was found. The present study demonstrates significant long-term improvement after a switch to incoBoNT/A in patients with preceding secondary treatment failure after abo- or onaBoNT/A therapy and confirms the low antigenicity of incoBoNT/A.
Asunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Espasticidad Muscular/tratamiento farmacológico , Fármacos Neuromusculares/uso terapéutico , Tortícolis/tratamiento farmacológico , Toxinas Biológicas/uso terapéutico , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Insuficiencia del TratamientoRESUMEN
The concept of "magic bullets", i [...].
Asunto(s)
Inmunotoxinas/uso terapéutico , Toxinas Biológicas/uso terapéutico , HumanosRESUMEN
The fascination and fear of snakes dates back to time immemorial, with the first scientific treatise on snakebite envenoming, the Brooklyn Medical Papyrus, dating from ancient Egypt. Owing to their lethality, snakes have often been associated with images of perfidy, treachery and death. However, snakes did not always have such negative connotations. The curative capacity of venom has been known since antiquity, also making the snake a symbol of pharmacy and medicine. Today, there is renewed interest in pursuing snake-venom-based therapies. This Review focuses on the chemistry of snake venom and the potential for venom to be exploited for medicinal purposes in the development of drugs. The mixture of toxins that constitute snake venom is examined, focusing on the molecular structure, chemical reactivity and target recognition of the most bioactive toxins, from which bioactive drugs might be developed. The design and working mechanisms of snake-venom-derived drugs are illustrated, and the strategies by which toxins are transformed into therapeutics are analysed. Finally, the challenges in realizing the immense curative potential of snake venom are discussed, and chemical strategies by which a plethora of new drugs could be derived from snake venom are proposed.
Asunto(s)
Medicina , Mordeduras de Serpientes , Toxinas Biológicas , Animales , Venenos de Serpiente/química , Serpientes , Mordeduras de Serpientes/tratamiento farmacológico , Toxinas Biológicas/uso terapéuticoRESUMEN
Given the vast number of venomous and poisonous animals, it is surprising that only relatively few animal-derived toxins have been explored and made their way into marketed drugs or are being investigated in ongoing clinical trials. In this review, we highlight marketed drugs deriving from animal toxins as well as ongoing clinical trials and preclinical investigations in the field. We emphasize that more attention should be paid to the rich supply of candidates that nature provides as valuable starting points for addressing serious unmet medical needs.
Asunto(s)
Toxinas Biológicas , Ponzoñas , Animales , Toxinas Biológicas/uso terapéutico , Ponzoñas/uso terapéuticoRESUMEN
Natural toxins are poisonous substances produced by bacteria, insects, animals, or plants [...].
Asunto(s)
Desarrollo de Medicamentos , Toxinas Biológicas/uso terapéutico , Animales , HumanosRESUMEN
Cancer cells frequently overexpress specific surface receptors providing tumor growth and survival which can be used for precise therapy. Targeting cancer cell receptors with protein toxins is an attractive approach widely used in contemporary experimental oncology and preclinical studies. Methods of targeted delivery of toxins to cancer cells, different drug carriers based on nanosized materials (liposomes, nanoparticles, polymers), the most promising designed light-activated toxins, as well as mechanisms of the cytotoxic action of the main natural toxins used in modern experimental oncology, are discussed in this review. The prospects of the combined therapy of tumors based on multimodal nanostructures are also discussed.
Asunto(s)
Neoplasias/tratamiento farmacológico , Toxinas Biológicas/uso terapéutico , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Humanos , Estrés Oxidativo/efectos de los fármacos , Toxinas Biológicas/efectos adversosRESUMEN
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.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Endometriosis/tratamiento farmacológico , Medicina Tradicional de Asia Oriental , Extractos de Tejidos/uso terapéutico , Toxinas Biológicas/uso terapéutico , Animales , Medicamentos Herbarios Chinos/efectos adversos , Endometriosis/metabolismo , Endometriosis/patología , Femenino , Humanos , Medicina Tradicional de Asia Oriental/efectos adversos , Extractos de Tejidos/efectos adversos , Toxinas Biológicas/efectos adversos , Resultado del Tratamiento , Ponzoñas/uso terapéuticoRESUMEN
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Here, we investigated the molecular mechanisms that underpin the anticancer effects of cleistanthin A (CA) in two CRC cell lines, HCT 116, and SW480. At 48 h, CA exhibited apoptotic cytotoxic effects in both CRC cell lines, concomitant with reduction of an anti-apoptotic protein, survivin. Mechanistically, CA treatment significantly reduced the expression levels of ß-catenin and active-ß-catenin in a dose-dependent manner in both CRC cell lines. Moreover, CA suppressed the Wnt/ß-catenin signaling pathway by decreasing ß-catenin-mediated transcriptional activity and expression of ß-catenin target genes, AXIN2, CCND1, and survivin. Furthermore, CA also inhibited transcriptional activity in cells overexpressing a constitutively active ß-catenin S33Y, indicating a GSK-3ß-independent mechanism underlying the observed CA effects on CRC cells. Although cytotoxic activity was not observed with CA treatment at 24 h, cell migration and invasion were significantly reduced. In addition, CA suppressed V-type ATPase activity and focal adhesion kinase (FAK) phosphorylation. Collectively, our study reveals that CA has time-dependent effects on CRC cell phenotypes. First, short-term CA treatment inhibited CRC cell migration and invasion partly through the suppression of V-type ATPase activity. This suppression resulted in reduced FAK activation. Second, longer-term CA treatment decreased cell viability which correlated with the suppression of Wnt/ß-catenin signaling induced transcriptional activity. Altogether, our data suggest that CA has the potential to develop as an effective and novel therapeutic drug for CRC patients.
Asunto(s)
Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Glicósidos/farmacología , Lignanos/farmacología , Toxinas Biológicas/farmacología , Apoptosis/fisiología , Movimiento Celular/fisiología , Neoplasias Colorrectales/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Glicósidos/uso terapéutico , Células HCT116 , Células HEK293 , Humanos , Lignanos/uso terapéutico , Invasividad Neoplásica/patología , Toxinas Biológicas/uso terapéutico , Vía de Señalización Wnt/efectos de los fármacos , Vía de Señalización Wnt/fisiologíaRESUMEN
Venomous animals have evolved toxins that interfere with specific components of their victim's core physiological systems, thereby causing biological dysfunction that aids in prey capture, defense against predators, or other roles such as intraspecific competition. Many animal lineages evolved venom systems independently, highlighting the success of this strategy. Over the course of evolution, toxins with exceptional specificity and high potency for their intended molecular targets have prevailed, making venoms an invaluable and almost inexhaustible source of bioactive molecules, some of which have found use as pharmacological tools, human therapeutics, and bioinsecticides. Current biomedically-focused research on venoms is directed towards their use in delineating the physiological role of toxin molecular targets such as ion channels and receptors, studying or treating human diseases, targeting vectors of human diseases, and treating microbial and parasitic infections. We provide examples of each of these areas of venom research, highlighting the potential that venom molecules hold for basic research and drug development.
Asunto(s)
Investigación Biomédica/métodos , Descubrimiento de Drogas/métodos , Péptidos/farmacología , Toxinas Biológicas/farmacología , Ponzoñas/farmacología , Animales , Desarrollo de Medicamentos/métodos , Humanos , Terapia Molecular Dirigida/métodos , Péptidos/química , Péptidos/uso terapéutico , Conformación Proteica , Toxinas Biológicas/química , Toxinas Biológicas/uso terapéutico , Ponzoñas/química , Ponzoñas/metabolismo , Ponzoñas/uso terapéuticoRESUMEN
Cardiovascular diseases such as coronary and peripheral artery diseases, venous thrombosis, stroke, hypertension, and heart failure are enormous burden to health and economy globally. Snake venoms have been the sources of discovery of successful therapeutics targeting cardiovascular diseases. For example, the first-in-class angiotensin-converting enzyme inhibitor captopril was designed largely based on bradykinin-potentiating peptides from Bothrops jararaca venom. In the recent years, sensitive and high throughput approaches drive discovery and cataloging of new snake venom toxins. As one of the largest class of snake venom toxin, there are now>700 sequences of three-finger toxins (3FTxs) available, many of which are yet to be studied. While the function of 3FTxs are normally associated with neurotoxicity, increasingly more 3FTxs have been characterized to have pharmacological effects on cardiovascular systems. Here we focus on this family of snake venom toxins and their potential in developing therapeutics against cardiovascular diseases.
Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Péptidos/uso terapéutico , Venenos de Serpiente/uso terapéutico , Toxinas Biológicas/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Bradiquinina/química , Captopril/química , Captopril/uso terapéutico , Desarrollo de Medicamentos/métodos , Humanos , Péptidos/química , Venenos de Serpiente/química , Toxinas Biológicas/químicaRESUMEN
The level of complexity in a disease like cancer presents a number of challenges for effective treatment development, which require significant innovation to overcome [...].
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Toxinas Biológicas/uso terapéutico , Animales , Antineoplásicos/efectos adversos , Antineoplásicos/historia , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Neoplasias/historia , Toxinas Biológicas/efectos adversos , Toxinas Biológicas/historiaRESUMEN
Many plants that are classed as poisonous also have therapeutic uses, and this is illustrated using members of the Drimia and Digitalis genera which are sources of cardiac glycosides.
Asunto(s)
Toxinas Biológicas/uso terapéutico , Glicósidos , Extractos Vegetales , Plantas , VenenosRESUMEN
Toxin peptides derived from the skin secretions of amphibians possess unique hypoglycemic activities. Many of these peptides share cationic and amphipathic structural similarities and appear to possess cell-penetrating abilities. The mechanism of their insulinotropic action is yet not elucidated, but they have shown great potential in regulating the blood glucose levels in animal models. Therefore, they have emerged as potential drug candidates as therapeutics for type 2 diabetes. Despite their anti-diabetic activity, there remain pharmaceutical challenges to be addressed for their clinical applications. Here, we present an overview of recent studies related to the toxin-derived anti-diabetic peptides derived from the skin secretions of amphibians. In the latter part, we introduce the bottleneck challenges for their delivery in vivo and general drug delivery strategies that may be applicable to extend their blood circulation time. We focus our research on the strategies that have been successfully applied to improve the plasma half-life of exendin-4, a clinically available toxin-derived anti-diabetic peptide drug.
Asunto(s)
Venenos de Anfibios/uso terapéutico , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Exenatida/uso terapéutico , Hipoglucemiantes/uso terapéutico , Toxinas Biológicas/uso terapéutico , Venenos de Anfibios/química , Venenos de Anfibios/farmacocinética , Animales , Biomarcadores/sangre , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Composición de Medicamentos , Exenatida/química , Exenatida/farmacocinética , Semivida , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacocinética , Toxinas Biológicas/química , Toxinas Biológicas/farmacocinéticaRESUMEN
Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system is common amongst young adults, leading to major personal and socioeconomic burdens. However, it is still considered complex and challenging to understand and treat, in spite of the efforts made to explain its etiopathology. Despite the discovery of many genetic and environmental factors that might be related to its etiology, no clear answer was found about the causes of the illness and neither about the detailed mechanism of these environmental triggers that make individuals susceptible to MS. In this review, we will attempt to explore the major contributors to MS autoimmunity including genetic, epigenetic and ecological factors with a particular focus on toxins, chemicals or drugs that may trigger, modify or prevent MS disease.