JOURNAL OF VENOMOUS ANIMALS AND TOXINS INCLUDING TROPICAL DISEASES

Effects of local and systemic treatment with human natural killer-1 mimetic peptide (HNK-1) after ventral root avulsion and reimplantation in mice
da Silva NS, Lombardi J, Kirchhoff F, Ferreira RS, Barraviera B, de Oliveira ALR and Cartarozzi LP
Spinal ventral root injuries generate significant motoneuron degeneration, which hinders full functional recovery. The poor prognosis of functional recovery can be attributed to the use or combination of different therapeutic approaches. Several molecules have been screened as potential treatments in combination with surgical reimplantation of the avulsed roots, the gold standard approach for such injuries. Among the studied molecules, human natural killer-1 (HNK-1) stands out as it is related to the stimulation of motor axon outgrowth. Therefore, we aimed to comparatively investigate the effects of local administration of an HNK-1 mimetic peptide (mp-HNK-1) and systemic treatment with ursolic acid (UA), another HNK-1 mimetic, after ventral root avulsion and reimplantation with heterologous fibrin biopolymer (HFB).
Heterologous fibrin biopolymer as an emerging approach to peripheral nerve repair: a scoping review
Muller KS, Tibúrcio FC, Ferreira RS, Barraviera B and Matheus SMM
Nerve injuries present a substantial challenge within the medical domain due to their prevalent occurrence and significant impact. In nerve injuries, a range of physiopathological and metabolic responses come into play to stabilize and repair the resulting damage. A critical concern arises from the disruption of connections at neuromuscular junctions, leading to profound degeneration and substantial loss of muscle function, thereby hampering motor tasks. While end-to-end neurorrhaphy serves as the established technique for treating peripheral nerve injuries, achieving comprehensive morphofunctional recovery remains a formidable challenge. In pursuit of enhancing the repair process, alternative and supportive methods are being explored. A promising candidate is the utilization of heterologous fibrin biopolymer, a sealant devoid of human blood components. Notably, this biopolymer has showcased its prowess in establishing a stable and protective microenvironment at the site of use in multiple scenarios of regenerative medicine. Hence, this scoping review is directed towards assessing the effects of associating heterologous fibrin biopolymer with neurorrhaphy to treat nerve injuries, drawing upon findings from prior studies disseminated through PubMed/MEDLINE, Scopus, and Web of Science databases. Further discourse delves into the intricacies of the biology of neuromuscular junctions, nerve injury pathophysiology, and the broader utilization of fibrin sealants in conjunction with sutures for nerve reconstruction procedures. The association of the heterologous fibrin biopolymer with neurorrhaphy emerges as a potential avenue for surmounting the limitations associated with traditional sealants while also mitigating degeneration in nerves, muscles, and NMJs post-injury, thereby fostering a more conducive environment for subsequent regeneration. Indeed, queries arise regarding the long-term regenerative potential of this approach and its applicability in reconstructive surgeries for human nerve injuries.
Acute phase reactions in venom and fraction-induced acute kidney injury: the role of oxidative stress and inflammatory pathways in rabbit and rabbit kidney models
Chaiyabutr N, Noiprom J, Promruangreang K, Vasaruchapong T, Laoungbua P, Khow O, Chanhome L and Sitprija V
This study examines the direct nephrotoxic effects of venom (RVV) and venom fractions in and isolated perfused kidneys (IPK) to understand the role of inflammation pathways and susceptibility to oxidative stress in venom or fraction-induced acute renal failure.
Delayed repair of the facial nerve and its negative impacts on nerve and muscle regeneration
Bueno CRS, Buchaim DV, Barraviera B, Ferreira RS, Santos PSDS, Reis CHB, Cini MA, Kuga MC, Rosa GM and Buchaim RL
In this experimental protocol, we evaluated the immediate and delayed repair of the buccal branch of the facial nerve (BBFN) with heterologous fibrin biopolymer (HFB) as a coaptation medium and the use of photobiomodulation (PBM), performing functional and histomorphometric analysis of the BBFN and perioral muscles.
Understanding the complexity of venom: A focus on high molecular weight components
de Oliveira IS, Alano-da-Silva NM, Ferreira IG, Cerni FA, Sachett JAG, Monteiro WM, Pucca MB and Arantes EC
scorpion is responsible for a significant number of envenomings in Brazil, ranging from mild to severe, and in some cases, leading to fatalities. While supportive care is the primary treatment modality, moderate and severe cases require antivenom administration despite potential limitations and adverse effects. The remarkable proliferation of scorpions, attributed to their biology and asexual reproduction, contributes to a high incidence of envenomation. scorpion venom predominantly consists of short proteins acting as neurotoxins (α and β), that primarily target ion channels. Nevertheless, high molecular weight compounds, including metalloproteases, serine proteases, phospholipases, and hyaluronidases, are also present in the venom. These compounds play a crucial role in envenomation, influencing the severity of symptoms and the spread of venom. This review endeavors to comprehensively understand the scorpion venom by elucidating the primary high molecular weight compounds and exploring their potential contributions to envenomation. Understanding these compounds' mechanisms of action can aid in developing more effective treatments and prevention strategies, ultimately mitigating the impact of scorpion envenomation on public health in Brazil.
Immunomodulatory effect of sp. in mononuclear cells extracted from the blood of rheumatoid arthritis patients
Tobar CGR, Urmendiz YDMM, Vallejo MA, Manquillo DF, Castaño VEN, Caicedo AIO, Tobar LLM, Vargas JAG and Cuellar RAD
Pathophysiological mechanisms of rheumatoid arthritis arise because of a proinflammatory environment, generated by the interaction of autoreactive lymphocytes and proinflammatory mediators. Current strategies to mitigate the progression of the disease produce adverse effects, so there is a need for new therapeutic strategies and molecular targets to treat this disease. In this context, evidence suggests that scorpion venoms could modulate the immune response and some important cellular mechanisms of pharmacological interest. To evaluate the immunomodulatory effect of the venom of sp. (a possible new species close to ) peripheral blood mononuclear cells of women diagnosed with RA were compared to cells of a control group.
spiders (Trechaleidae) from southern Mexico: DNA barcoding, venomics, and biological effect
Padilla-Villavicencio M, Corzo G, Guillén-Navarro K, Ibarra-Núñez G, Arenas I, Zamudio F and Diego-García E
Members of the genus Simon, 1891 are categorized as wandering spiders and are part of the family Trechaleidae. The genomics and proteomics of spiders from North America remain uncharacterized. The present study explores for the first time molecular data from the endemic species Medina, 2006, and also presents new data for (Keyserling, 1878), both collected in southern Mexico.
Skin secretions of Leptodactylidae (Anura) and their potential applications
Carrillo JFC, Boaretto AG, Santana DJ and Silva DB
The skin of anuran species is a protective barrier against predators and pathogens, showing also chemical defense by substances that represent a potential source for bioactive substances. This review describes the current chemical and biological knowledge from the skin secretions of Leptodactylidae species, one of the most diverse neotropical frog families. These skin secretions reveal a variety of substances such as amines (12), neuropeptides (16), and antimicrobial peptides (72). The amines include histamine and its methylated derivatives, tryptamine derivatives and quaternary amines. The peptides of Leptodactylidae species show molecular weight up to 3364 Da and ocellatins are the most reported. The peptides exhibit commonly glycine (G) or glycine-valine (GV) as C-terminal amino acids, and the most common N-terminal amino acids are glutamic acid (E), lysine (K), and valine (V). The substances from Leptodactylidae species have been evaluated against pathogenic microorganisms, particularly and , and the most active peptides showed MIC of 1-15 µM. Furthermore, some compounds showed also pharmacological properties such as immunomodulation, treatment of degenerative diseases, anticancer, and antioxidant. Currently, only 9% of the species in this family have been properly studied, highlighting a large number of unstudied species such as an entire subfamily (Paratelmatobiinae). The ecological context, functions, and evolution of peptides and amines in this family are poorly understood and represent a large field for further exploration.
Identification and analgesic activity study of analgesic protein Ⅶ-2 from venom
Sun Y, Zhang GB, Li S, Liu XY, Chen L and Bao PJ
Acid-sensing ion channel 1a (ASIC1a) plays a critical role in physiological and pathological processes. To further elucidate the biological functions of ASICs and their relationships with disease occurrence and development, it is advantageous to investigate and develop additional regulatory factors for ASICs.
Electrophysiological evaluation of the effect of peptide toxins on voltage-gated ion channels: a scoping review on theoretical and methodological aspects with focus on the Central and South American experience
Rojas-Palomino J, Gómez-Restrepo A, Salinas-Restrepo C, Segura C, Giraldo MA and Calderón JC
The effect of peptide toxins on voltage-gated ion channels can be reliably assessed using electrophysiological assays, such as the patch-clamp technique. However, much of the toxinological research done in Central and South America aims at purifying and characterizing biochemical properties of the toxins of vegetal or animal origin, lacking electrophysiological approaches. This may happen due to technical and infrastructure limitations or because researchers are unfamiliar with the techniques and cellular models that can be used to gain information about the effect of a molecule on ion channels. Given the potential interest of many research groups in the highly biodiverse region of Central and South America, we reviewed the most relevant conceptual and methodological developments required to implement the evaluation of the effect of peptide toxins on mammalian voltage-gated ion channels using patch-clamp. For that, we searched MEDLINE/PubMed and SciELO databases with different combinations of these descriptors: "electrophysiology", "patch-clamp techniques", "Ca channels", "K channels", "cnidarian venoms", "cone snail venoms", "scorpion venoms", "spider venoms", "snake venoms", "cardiac myocytes", "dorsal root ganglia", and summarized the literature as a scoping review. First, we present the basics and recent advances in mammalian voltage-gated ion channel's structure and function and update the most important animal sources of channel-modulating toxins (e.g. cnidarian and cone snails, scorpions, spiders, and snakes), highlighting the properties of toxins electrophysiologically characterized in Central and South America. Finally, we describe the local experience in implementing the patch-clamp technique using two models of excitable cells, as well as the participation in characterizing new modulators of ion channels derived from the venom of a local spider, a toxins' source less studied with electrophysiological techniques. Fostering the implementation of electrophysiological methods in more laboratories in the region will strengthen our capabilities in many fields, such as toxinology, toxicology, pharmacology, natural products, biophysics, biomedicine, and bioengineering.
Snake venom bioprospecting as an approach to finding potential anti-glioblastoma molecules
Orozco-Mera J, Montoya-Gómez A, Lopes DS and Jiménez-Charris E
Glioblastoma (GB) is the most common type of malignant tumor of the central nervous system, responsible for significant morbidity and with a 5-year overall relative survival of only 6.8%. Without advances in treatment in the last twenty years, the standard of care continues to be maximum safe resection, Temozolomide (TMZ), and radiotherapy. Many new trials are ongoing, and despite showing increased progression-free survival, these trials did not improve overall survival. They did not consider the adverse effects of these therapies. Therefore, an increasing number of bioprospecting studies have used snake venom molecules to search for new strategies to attack GB selectively without producing side effects. The present review aims to describe GB characteristics and current and new approaches for treatment considering their side effects. Besides, we focused on the antitumoral activity of snake venom proteins from the Viperidae family against GB, exploring the potential for drug design based on and studies. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. In January 2024, a systematic search was performed in the PubMed, EMBASE, and Web of Science databases from January 2000 to December 2023. Search terms were selected based on the population/exposure/outcome (PEO) framework and combined using Boolean operators ("AND", "OR"). The search strategy used these terms: glioblastoma, glioma, high-grade glioma, WHO IV glioma, brain cancer, snake venom, Viperidae, and bioprospection. We identified 10 and studies with whole and isolated proteins from Viperidae venom that could have antitumor activity against glioblastoma. Studies in bioprospecting exploring the advantage of snake venom proteins against GB deserve to be investigated due to their high specificity, small size, inherent bioactivity, and few side effects to cross the blood-brain barrier (BBB) to reach the tumor microenvironment.
Prevalence of elephantiasis, an overlooked disease in Southern Africa: a comprehensive review
Lamula SQ, Aladejana EB, Aladejana EA and Buwa-Komoreng LV
Elephantiasis, also known as lymphatic filariasis (LF), is a debilitating condition characterized by the thickening of the skin and muscles, primarily affecting the limbs, genitalia, and female breasts. Lymphatic filariasis is a major global health concern, affecting approximately 120 million people worldwide and having a significant impact on people's quality of life, mobility, and socio-economic status. Although LF is endemic in many parts of the world, including Africa, it is a neglected issue in Southern Africa, with little information available. According to the World Health Organisation, approximately 882.5 million people in 44 countries worldwide are at risk of contracting LF, making it the second most common vector-borne disease after malaria. The primary goal of this review was to assess the prevalence of elephantiasis in the Southern African Development Community (SADC) region. Lymphatic filariasis is endemic in four of the sixteen SADC countries, three countries have administered MDA to the population that required it and they are now under post-intervention surveillance, while LF is no longer a public health problem in Malawi. Global efforts to eliminate LF have been hampered by the non-availability of MDA in some SADC countries such as Angola, Mozambique, Zambia, and Zimbabwe. Despite the implementation of mass drug administration programs, a review of the literature reveals gaps in knowledge about LF prevalence cases in SADC countries. Each country faces unique challenges and successes in combating LF due to varying levels of available data and healthcare infrastructure. Some SADC countries continue to bear the burden of LF-related diseases, necessitating ongoing disease prevention and elimination efforts. This review emphasizes the importance of ongoing research, data collection, and novel policies to combat the spread of elephantiasis disease in the SADC region and beyond.
Human visceral leishmaniasis and polymorphisms in interleukin-coding genes: a systematic review
Vieira AVB, de Menezes MR, Farias PCS, da Silva ED, Bezerra GSN, Barbosa WL and de Medeiros ZM
Visceral leishmaniasis (VL) is a neglected disease that is typical of tropical and subtropical parts of the world and is caused by the trypanosomatid complex. This disease is a multifactorial condition that involves parasitic, environmental, and immunogenetic characteristics. Genetic changes in genes encoding cytokines may be associated with changes in their expression and, consequently, with the development of clinical resistance or susceptibility to the disease. This systematic review and meta-analysis aimed to assess whether single nucleotide polymorphisms (SNPs) in interleukin genes influence the clinical consequences of visceral leishmaniasis infection. To this end, we carried out a systematic review and meta-analysis with structured searches in the EMBASE, PubMed, Scopus, SciELO, and Web of Science databases without time restrictions. Two independent reviewers examined the studies, performed data extraction, and assessed quality by assigning scores. If there were any discrepancies, a third reviewer with more experience was consulted. After the screening process, 28 articles were included in the systematic review and 9 in the final analysis of the meta-analysis. Statistical analyses were carried out using various genetic models. The odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated to estimate the associations. Overall, the main clinical outcomes were classified as not associated or associated when they presented susceptibility, resistance, risk, or protective factors for the development of the disease. Associations between IFN-γ +874T/A polymorphisms in the dominant model (OR 1.64, 95% CI 1.13-2.38, I = 0%, p < 0.01) and heterozygous model (OR 1.72, 95% CI 1.15-2.57, I = 0%, p < 0.01) and IL-18 -137G/C in the recessive model (OR 1.33, 95% CI 1.02-1.71, I = 9%, p = 0.03) and VL were observed. For the IL-10 gene SNPs, there was no significant association. Our findings suggest that SNPs in the IFN-γ and IL-18 genes may be associated with the risk of developing VL.
Cytotoxic effects of crotoxin from snake in canine mammary tumor cell lines
Pedro G, Brasileiro FCDS, Macedo JM, Soares AM, Mafra GC, Alves CEF and Laufer-Amorim R
Mammary gland tumors are the most prevalent neoplasm in intact female dogs, and they are good natural models to study comparative oncology. Most canine mammary malignancies, as in women, are commonly refractory to conventional therapies and demand continuous new therapeutic approaches. , also called rattlesnake, has more than 60 different proteins in its venom with multiple pharmaceutical uses, such as antitumor, antiviral, and antimicrobial action. Crotoxin, a potent β-neurotoxin formed by the junction of two subunits, a basic subunit (CB-PLA) and an acidic subunit (crotapotin), has already been reported to have anticancer properties in different types of cancers.
Protective effects of mesenchymal stromal cell-derived secretome on dermonecrosis induced in rabbits by spider venom
Rodrigues GM, de Almeida ME, Marcelino SAC, Fernandes PBU, da Cruz JOP, Araújo FL, Ferreira RDS, Botelho AFM, Bedoya FJ, Cahuana GM, Hitos AB, Soria B, Costal-Oliveira F, Duarte CG, Tejedo JR, Chávez-Olórtegui C and Melo MM
Loxoscelism refers to a set of clinical manifestations caused by the bite of spiders from the genus. The classic clinical symptoms are characterized by an intense inflammatory reaction at the bite site followed by local necrosis and can be classified as cutaneous loxoscelism. This cutaneous form presents difficult healing, and the proposed treatments are not specific or effective. This study aimed to evaluate the protective effect of mesenchymal stromal cells-derived secretome on dermonecrosis induced by spider venom in rabbits.
An overview of some enzymes from buthid scorpion venoms from Colombia: and n. sp. aff.
Mendoza-Tobar LL, Clement H, Arenas I, Sepulveda-Arias JC, Vargas JAG and Corzo G
In Colombia, several species of Buthidae scorpions belonging to the genera and coexist, and their stings are considered life-threatening to humans because of their venom neurotoxins. Despite previous studies focusing on neurotoxins from these scorpion genera, little is known about the enzymes present in their venoms and their relationship with whole venom toxicity.
An improved high-performance liquid chromatography (HPLC) method for detection of variations in the hydroxyproline content of tissue homogenates from -infected mice
Gidlund MA, Molina RFS and Burger E
Paracoccidioidomycosis (PCM) is a severe granulomatous disease The hallmark of this mycosis is fibrin degradation and granuloma formation as a result of a wound-healing process in the context of excessive inflammation. Therefore, as the content of collagen can be assessed by the methodology described in this manuscript, we propose that the content of hydroxyproline (HYP) be employed as a new and efficient measurement of granulomatous lesions developed. To estimate the level of HYP the major byproduct of the degradation process, we hypothesized that this simple and efficient technique could serve as a marker of disease severity.
Activation of M1 muscarinic acetylcholine receptors by proline-rich oligopeptide 7a (
Alberto-Silva C, Pantaleão HQ, da Silva BR, da Silva JCA and Echeverry MB
The bioactive peptides derived from snake venoms of the Viperidae family species have been promising as therapeutic candidates for neuroprotection due to their ability to prevent neuronal cell loss, injury, and death. Therefore, this study aimed to evaluate the cytoprotective effects of a synthetic proline-rich oligopeptide 7a (PRO-7a;
Fraction of venom containing crotapotin protects PC12 cells against MPP toxicity by activating the NGF-signaling pathway
Bernardes CP, Lopes Pinheiro E, Ferreira IG, de Oliveira IS, Dos Santos NAG, Sampaio SV, Arantes EC and Dos Santos AC
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. There is no effective treatment for neurodegenerative diseases. Snake venoms are a cocktail of proteins and peptides with great therapeutic potential and might be useful in the treatment of neurodegenerative diseases. Crotapotin is the acid chain of crotoxin, the major component of venom. PD is characterized by low levels of neurotrophins, and synaptic and axonal degeneration; therefore, neurotrophic compounds might delay the progression of PD. The neurotrophic potential of crotapotin has not been studied yet.
Molecular genetic association of rs8099917 and rs1800795 polymorphisms in the progression of hepatitis Delta virus liver disease
Passos-Silva AM, Silva ECE, Borzacov LMP, Araújo A, Porto AS, Salcedo JMV and Vieira D
The relationship between viral infections and host factors holds high hopes for identifying the role of Interferon Lambda 3 (IFNL3) and Interleukin 6 (IL-6) polymorphisms in the development of Chronic Liver Disease (CLD) in patients infected with hepatitis Delta virus (HDV) in the Western Brazilian Amazon.
Isolation and cDNA cloning of four peptide toxins from the sea anemone
Homma T, Ishida M, Nagashima Y and Shiomi K
Sea anemones are well known to contain multiple peptide toxins. However, of more than 1100 species of sea anemones distributed worldwide, only a little over 50 have been studied for peptide toxins. Therefore, innumerable unique and novel peptide toxins remain to be discovered in unstudied sea anemones.