Spider Venom Research Articles

The use of therapeutic plasma exchange in systemic loxoscelism induced treatment resistant hemolytic anemia: A case report

Brown recluse spider bites can lead to severe reactions such as skin necrosis,hemolytic anemia, and multiorgan failure, which can be life-threatening. Therapeutic plasma exchange has been reported to provide clinical benefit for such cases. In thisreport, we present a case of a brown recluse spider bite that was successfully treated with therapeutic plasma exchange and compare it with previous case reports.

Loxosceles amazonica Brown Spider venom: Insights into enzymatic activities, immunorecognition, and novel phospholipase D isoforms

The Loxosceles genus represents one of the main arachnid genera of medical importance in Brazil. Despite the gravity of Loxosceles-related accidents, just a handful of species are deemed medically important and only a few have undergone comprehensive venom characterization. Loxosceles amazonica is a notable example of a potentially dangerous yet understudied Loxosceles species. While there have been limited reports of accidents involving L. amazonica to date, accidents related to Loxosceles are increasing in the North and Northeast regions of Brazil, where L. amazonica has been reported. In this work, we provide a complementary biochemical and immunological characterization of L. amazonica venom, considering its most relevant enzymatic activities and its immunorecognition and neutralization by current therapeutic antivenoms. Additionally, a cDNA library enriched with phospholipase D (PLD) sequences from L. amazonica venom glands was built and subsequently sequenced. The results showed that L. amazonica venom is well immunorecognised by all the tested antibodies. Its venom also displayed proteolytic, hyaluronidase, and sphingomyelinase activities. These activities were at least partially inhibited by available antivenoms. With cDNA sequencing of PLDs, seven new putative isoforms were identified in the venom of L. amazonica. These results contribute to a better knowledge of the venom content and activities of a synanthropic, yet understudied, Loxosceles species. In vivo assays are essential to confirm the medical relevance of L. amazonica, as well as to assess its true toxic potential and elucidate its related pathophysiology.

Identification and Evolutionary Analysis of the Widely Distributed CAP Superfamily in Spider Venom.

Venom plays a crucial role in the defense and predation of venomous animals. Spiders (Araneae) are among the most successful predators and have a fascinating venom composition. Their venom mainly contains disulfide-rich peptides and large proteins. Here, we analyzed spider venom protein families, utilizing transcriptomic and genomic data, and highlighted their similarities and differences. We show that spiders have specific combinations of toxins for better predation and defense, typically comprising a core toxin expressed alongside several auxiliary toxins. Among them, the CAP superfamily is widely distributed and highly expressed in web-building Araneoidea spiders. Our analysis of evolutionary relationships revealed four subfamilies (subA-subD) of the CAP superfamily that differ in structure and potential functions. CAP proteins are composed of a conserved CAP domain and diverse C-terminal domains. CAP subC shares similar domains with the snake ion channel regulator svCRISP proteins, while CAP subD possesses a sequence similar to that of insect venom allergen 5 (Ag5). Furthermore, we show that gene duplication and selective expression lead to increased expression of CAP subD, making it a core member of the CAP superfamily. This study sheds light on the functional diversity of CAP subfamilies and their evolutionary history, which has important implications for fully understanding the composition of spider venom proteins and the core toxin components of web-building spiders.

Does Covid-19 influence the dynamics of envenomation by animals in a country strongly affected by both conditions? Epidemiological data from Brazil

The impact of Covid-19 on envenomations by venomous animals in countries heavily affected by both conditions has not been quantified yet. Brazil shows high incidence of envenomations by scorpions, spiders and snakes and was heavily affected by waves of Covid-19. To determine how the pandemic impacted the epidemiology of envenomations by those three groups of venomous animals, we used online databases from two surveillance sources on number of cases and mortality. During the years before and during the pandemic, scorpion stings typically occurred in adults of both sexes in urban zones in the Southeast and Northeast regions. Spider bites occurred mainly in the South region, in adults of both sexes in urban zone. Snakebites affected mainly rural adult men in the Amazon. Between 2007 and 2021, overall incidence of cases by scorpions, spiders and snakes decreased after the beginning of the pandemic, snakebites did not show changes after the pandemic started in Brazil, but cases by scorpions and spiders decreased. No changes in the incidence of deaths were observed. On national level, Covid-19 affected some demographic, clinical and epidemiological aspects in cases by scorpions, spiders and snakes.

Spider and Wasp Acylpolyamines: Venom Components and Versatile Pharmacological Leads, Probes, and Insecticidal Agents.

Polyamines (PAs) are polycationic biogenic amines ubiquitously present in all life forms and are involved in molecular signaling and interaction, determining cell fate (e.g., cell proliferation, dif-ferentiation, and apoptosis). The intricate balance in the PAs' levels in the tissues will determine whether beneficial or detrimental effects will affect homeostasis. It's crucial to note that endoge-nous polyamines, like spermine and spermidine, play a pivotal role in our understanding of neu-rological disorders as they interact with membrane receptors and ion channels, modulating neuro-transmission. In spiders and wasps, monoamines (histamine, dopamine, serotonin, tryptamine) and polyamines (spermine, spermidine, acyl polyamines) comprise, with peptides and other sub-stances, the low molecular weight fraction of the venom. Acylpolyamines are venom components exclusively from spiders and a species of solitary wasp, which cause inhibition chiefly of iono-tropic glutamate receptors (AMPA, NMDA, and KA iGluRs) and nicotinic acetylcholine receptors (nAChRs). The first venom acylpolyamines ever discovered (argiopines, Joro and Nephila toxins, and philanthotoxins) have provided templates for the design and synthesis of numerous analogs. Thus far, analogs with high potency exert their effect at nanomolar concentrations, with high se-lectivity toward their ionotropic and ligand receptors. These potent and selective acylpolyamine analogs can serve biomedical purposes and pest control management. The structural modification of acylpolyamine with photolabile and fluorescent groups converted these venom toxins into use-ful molecular probes to discriminate iGluRs and nAchRs in cell populations. In various cases, the linear polyamines, like spermine and spermidine, constituting venom acyl polyamine backbones, have served as cargoes to deliver active molecules via a polyamine uptake system on diseased cells for targeted therapy. In this review, we examined examples of biogenic amines that play an essential role in neural homeostasis and cell signaling, contributing to human health and disease outcomes, which can be present in the venom of arachnids and hymenopterans. With an empha-sis on the spider and wasp venom acylpolyamines, we focused on the origin, structure, derivatiza-tion, and biomedical and biotechnological application of these pharmacologically attractive, chemically modular venom components.

Spider bite presenting as fever, macrophage activation syndrome and a skin ulcer

Introduction: Fever of unknown origin (FUO) refers to a condition of prolonged increased body temperature, without identified causes. The most common cause of FUO worldwide are infections; arthropod bites (loxoscelism) should be considered in view of the spread of the fiddleback spider. Loxoscelism can present in a cutaneous form (a necrotic cutaneous ulcer) or in a systemic form with fever, haemolytic anaemia, rhabdomyolysis and, rarely, macrophage activation syndrome (MAS). For this suspicion, it is important to have actually seen the spider. Case description: A 71-year-old man was admitted to our department because of intermittent fever, arthralgia and a necrotic skin lesion on his right forearm that appeared after gardening. Laboratory tests were negative for infectious diseases, and several courses of antibiotics were administered empirically without clinical benefit. Whole-body computed tomography showed multiple colliquative lymphadenomegalies, the largest one in the right axilla, presumably of reactive significance. A shave biopsy of the necrotic lesion was performed: culture tests were negative and histological examination showed non-specific necrotic material, so a second skin and lymph node biopsy was performed. The patient developed MAS for which he received corticosteroid therapy with clinical/laboratory benefit. Cutaneous and systemic loxoscelism complicated by MAS was diagnosed. Subsequently, the second biopsy revealed morphological and immunophenotypic findings consistent with primary cutaneous anaplastic large cell lymphoma (PC-ALCL). Conclusions: Skin lesions and lymphadenomegalies of unknown origin should always be biopsied. It is very common to get indeterminate results, but this does not justify not repeating the procedure to avoid misdiagnosis.

A novel spider venom peptide from the predatory mite Neoseiulus barkeri shows lethal effect on phytophagous pests

The long-term use of pesticides in the field, and the high fertility and adaptability of phytophagous mites have led to resistance problems; consequently, novel safe and efficient active substances are necessary to broaden the tools of pest mite control. Natural enemies of arthropods typically secrete substances with paralytic or lethal effects on their prey, and those substances are a resource for future biopesticides. In this study, two putative venom peptide genes were identified in a parasitic mite Neoseiulus barkeri transcriptome. Recombinant venom NbSP2 peptide injected into Tetranychus cinnabarinus mites was significantly more lethal than recombinant NBSP1. NbSP2 was also lethal to Spodoptera litura when injected but not when fed to third instar larvae. The interaction proteins of NbSP2 in T. cinnabarinus and S. litura were identified by affinity chromatography. Among these proteins, ATP synthase subunit β (ATP SSβ) was deduced as a potential target. Four binding sites were predicted between NBSP2 and ATP SSβ of T. cinnabarinus and S. litura. In conclusion, we identified a venom peptide with activity against T. cinnabarinus and S. litura. This study provides a novel component for development of a new biological pesticide.

STUDY OF ACUTE AND SUB-ACUTE TOXICITY OF A MEDICATION BASED ON SPIDER VENOM EXTRACT

Homeopathy is a regulatory therapy. The effectiveness of homeopathic therapy does not depend on the dose of the drug, but on the frequency of its repetitions. The composition of homeopathic preparations includes a wide range of natural and synthetic active substances: minerals; chemical substances; substances of plant origin; microorganisms, including fungi, bacteria, viruses, and plant parasites; substances of animal origin; and human materials, which may include tissues, secretions, hormones, and genetically homogeneous cell lines. One such substance is an extract of spider venom (Tarantul cubensis D6), which remains active in pharmaceutical preparation for a long time. The drug is selectively absorbed in inflamed tissues, differentiating them from healthy cells and suppressing inflammation. The drug is also effective in necrotic and proliferative processes. It is used for the treatment of panaritium in the initial stage, skin ulcers, necrobacillosis, and necrosis of the soft tissues of the animal. Any materials of animal or human origin are potentially dangerous for human and animal health, as they may contain toxic or pathogenic substances. Therefore, the study of the acute and subacute toxicity of spider venom extract is one of the stages of establishing the toxicological parameters of the drug. The use of the drug in a therapeutic dose caused an increase in animal body weight, hemoglobin concentration, number of leukocytes, erythrocytes, hematocrit value, average erythrocyte volume (MCV), average hemoglobin content in erythrocytes (МСН), average concentration of hemoglobin in erythrocytes (МСНС), number of platelets, and AST activity against the background of a slight decrease in total protein content, creatinine, urea, and ALT activity. The use of the drug in a 10-fold therapeutic dose caused an increase in animal body weight, creatinine, urea, ALT, and AST activity against the background of a decrease in the concentration of hemoglobin, the number of leukocytes and erythrocytes, the value of hematocrit, the average volume of erythrocytes (MCV), the average content of hemoglobin in erythrocytes (МСН), the average concentration of hemoglobin in erythrocytes (МСНС), the number of platelets, and the content of total protein.

Socio-cultural beliefs and perceptions influencing diagnosis and treatment of breast cancer among women in Ghana: a systematic review

BackgroundBreast cancer is currently the most commonly diagnosed cancer in Ghana and the leading cause of cancer mortality among women. Few published empirical evidence exist on cultural beliefs and perceptions about breast cancer diagnosis and treatment in Ghana. This systematic review sought to map evidence on the socio-cultural beliefs and perceptions influencing the diagnosis and treatment of breast cancer among Ghanaian women.MethodsThis review was conducted following the methodological guideline of Joanna Briggs Institute and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses. The literature search was conducted in PubMed, CINAHL via EBSCOhost, PsycINFO, Web of Science, and Embase. Studies that were conducted on cultural, religious, and spiritual beliefs were included. The included studies were screened by title, abstract, and full text by three reviewers. Data were charted and results were presented in a narrative synthesis form.ResultsAfter the title, abstract, and full-text screening, 15 studies were included. Three categories were identified after the synthesis of the charted data. The categories included: cultural, religious and spiritual beliefs and misconceptions about breast cancer. The cultural beliefs included ancestral punishment and curses from the gods for wrongdoing leading to breast cancer. Spiritual beliefs about breast cancer were attributed to spiritual or supernatural forces. People had the religious belief that breast cancer is a test from God and they resorted to prayers for healing. Some women perceived that breast cancer is caused by spider bites, heredity, extreme stress, trauma, infections, diet, or lifestyle.ConclusionThis study adduces evidence of the socio-cultural beliefs that impact on the diagnosis and treatment of breast cancer among women in Ghana. Taking into consideration the diverse cultural and traditional beliefs about breast cancer diagnosis and treatment, there is a compelling need to intensify nationwide public education on breast cancer to clarify the myths and misconceptions about the disease. We recommend the need to incorporate socio-cultural factors influencing breast cancer diagnosis and treatment into breast cancer awareness programs, education, and interventions in Ghana.

Study of the Bionomy and the Therapeutic Potential of a Substance Obtained from Spider Venom (Arthropoda: Araneae)

Venom is present in most spiders in the world, only two groups of venomous spiders are known and their chemical composition varies greatly between species. The vast majority have venom that is not very toxic to the human body, as is the case with crabs. However, the venom of other spiders affects humans more seriously. This manuscript aims to verify the bionomics of spiders and their therapeutic potential (Arthropoda: Araneae). Regarding the type of research source, As for the type of research source, it was worked with scientific articles published in national and international magazines. This type of production is commonly the most valued in all bibliographic production and is the easiest to access. Access to articles was through virtual libraries such as SciELO, the University of São Paulo, Latin American Literature, and the University of Brasília. This library has a specific section for Hymenoptera, with journals and article texts available in full. Considering only this section constitutes a limitation of the study since articles belonging to journals that are part of other sections of the electronic library could also contribute to the discussion of the production of knowledge. However, in principle, within these articles, there could not necessarily be a discussion focused on biology, ecology, and taxonomy.

Does black widow spider bite the heart?

BackgroundBlack widow spider (BWS) bites account for 0.5 % of global poisonings and 21 % of poisonings in North-East Iran. In addition to local reactions, systemic cardiovascular manifestations are likely to occur. ObjectiveThis study aims to present cases of patients who experienced cardiac symptoms after being envenomed by BWS. MethodsA descriptive retrospective cross-sectional evaluation was conducted on all patients who were bitten by a BWS in 2020 and presented with cardiac manifestations. They were referred to our tertiary pediatric cardiology center in Mashhad, Iran for evaluation. All accessible variables including history, physical examination, laboratory tests prioritizing cardiology, as well as electrocardiography and echocardiography findings, were evaluated. ResultSix patients, ranging in age from 5.5 to 13 years old, were bitten by BWS. None of the patients had a past or drug history and were admitted due to pain complaints at various bite sites that radiated in different directions. Four patients showed signs of tachycardia, and two showed hypertension, but no signs of infection were observed. Half of the patients experienced systemic complications. Upon arrival at the hospital, four patients showed elevated CKMB levels, which decreased during their hospitalization. Troponin I and N-Terminal Pro B-type Natriuretic Peptide levels were high in all patients. One patient with unstable hemodynamics showed pro-BNP over 35,000. T wave inversion was observed in six patients, ST segment depression in three patients, and ST-segment elevation in one patient, with overlap between them. ConclusionTaking notice of cardiovascular presentations after a BWS bite is considerable.

Genetically encoded libraries and spider venoms as emerging sources for crop protective peptides.

Agricultural crops are targeted by various pathogens (fungi, bacteria, and viruses) and pests (herbivorous arthropods). Antimicrobial and insecticidal peptides are increasingly recognized as eco-friendly tools for crop protection due to their low propensity for resistance development and the fact that they are fully biodegradable. However, historical challenges have hindered their development, including poor stability, limited availability, reproducibility issues, high production costs, and unwanted toxicity. Toxicity is a primary concern because crop-protective peptides interact with various organisms of environmental and economic significance. This review focuses on the potential of genetically encoded peptide libraries like the use of two-hybrid-based methods for antimicrobial peptides identification and insecticidal spider venom peptides as two main approaches for targeting plant pathogens and pests. We discuss some key findings and challenges regarding the practical application of each strategy. We conclude that genetically encoded peptide library- and spider venom-derived crop protective peptides offer a sustainable and environmentally responsible approach for addressing modern crop protection needs in the agricultural sector.

Comparative medical importance of spider bites in Spain over 1997-2020: a retrospective study based on hospital cases coded using ICD.

Envenomation by terrestrial toxic animals is considered a serious risk to human health worldwide. Snakes, hymenopterans, spiders, and scorpions have mainly attracted the attention of medical literature. However, the relative importance of spiders has been studied only in a few countries. Here, we present the first retrospective study on the incidence of spider bites requiring hospital care in Spain, compared to bites or stings from snakes, hymenopterans, and scorpions. Using ICD9MC and ICD10 databases from the World Health Organization's International Classification of Diseases for the period 1997-2020, we quantified the cases of envenomation by spiders, compared to those by other terrestrial toxic animals, the demographic data of envenomation cases, the relative severity of spider bites, and the geographic distribution of envenomation cases. Overall, the incidence of acute intoxication by terrestrial toxic animals in Spain was ca. 1.23 cases per million inhabitants. In decreasing order of importance, cases were due to snakes, hymenopterans, spiders, scorpions, and myriapods. Fatal cases were extremely rare, caused mainly by hymenopterans. No fatalities were caused by spiders, scorpions, and myriapods. A greater incidence of snake bites occurred in northern Spain, but no geographical trends were found for spider bites or scorpion stings. Severe poisoning or life-threatening cases due to bites or stings from toxic terrestrial animals in Spain seems to be very low, especially for spiders, compared to other countries in the world. In general, spiders do not present a risk to human health and should not be considered a major driver of morbidity.

Probable cutaneous-hemolytic loxoscelism

This study delves into loxoscelism, a condition arising from the bites of Loxosceles spiders. The case revolves around a 53-year-old woman who encountered systemic toxicity marked by dermal necrosis, hemolysis, and acute kidney injury. Timely medical intervention, incorporating surgical procedures and a meropenem regimen, resulted in nearly complete recovery. The report underscores the imperative for heightened awareness, early diagnosis, and appropriate treatment to alleviate complications linked to loxoscelism.

Garcinol: A novel and potent inhibitor of hyaluronidase enzyme

Extracellular matrix (ECM) contains hyaluronic acid (HA) as its integral part that is involved in numerous functional activities within the body. Degradation of HA by hyaluronidase enzyme involved in many pathophysiological conditions such as asthma, arthritis, COPD and in venom spreading during envenomation. Inhibitor of hyaluronidase enzyme has a wide range of application along with the hyaluronan-hyaluronidase system. In this present study, we have evaluated the inhibitory effect of garcinol against hyaluronidase from Hippasa partita spider venom (HPHyal), bovine testicular hyaluronidase (BTH) and human serum hyaluronidase. Garcinia indica fruit rind has been used to isolate the active component garcinol. Garcinol has been used in treatment of diverse ailments. Garcinol has exhibited anti-oxidant, anti-inflammatory, HAT inhibition and miRNA deregulator in development and progression of cancers. Experimental data have shown that garcinol completely inhibited all the three tested hyaluronidase enzymes. The inhibition was found to be non-competitive pattern with reversible type. In the docking study, garcinol with hyaluronidase enzyme has been stabilized by hydrogen bonding and hydrophobic interactions. Thus, garcinol could be a potent novel inhibitor of hyaluronidase enzyme which can be further used for pharmacotherapeutic applications.

Recluse Spider Bite (Loxosceles sp.): A case report from Jordan

Introduction: Loxosceles is a genus of spiders belongs to the family Sicariidae, known as recluse spiders. These spiders are considered venomous and are distinguished by three pairs of eyes, arranged in triangular pattern. In Jordan, only Loxosceles rufescens was recorded.
 Case Report: A 75-year-old female with history of hypertension was bitten by a recluse spider. The case developed cellulitis and secondary infection at the site of the bite. The patient showed no response to the treatment with antibiotics either at home or in the emergency department. She was admitted as an inpatient and given Tinam (Cephalosporin / 4th generation). The patient left the hospital after improvement of the symptoms on day 14.
 Conclusion: Bite of Loxosceles spider cause serious poisoning and lead to severe skin infection that needs hospitalization.

The funnel-web spider venom derived single knot peptide Hc3a modulates acid-sensing ion channel 1a desensitisation

Acid-sensing ion channel 1a (ASIC1a) is a proton-gated channel involved in synaptic transmission, pain signalling, and several ischemia-associated pathological conditions. The spider venom-derived peptides PcTx1 and Hi1a are two of the most potent ASIC1a inhibitors known and have been instrumental in furthering our understanding of the structure, function, and biological roles of ASICs. To date, homologous spider peptides with different pharmacological profiles at ASIC1a have yet to be discovered. Here we report the characterisation of Hc3a, a single inhibitor cystine knot peptide from the Australian funnel-web spider Hadronyche cerberea with sequence similarity to PcTx1. We show that Hc3a has complex pharmacology and binds different ASIC1a conformational states (closed, open, and desensitised) with different affinities, with the most prominent effect on desensitisation. Hc3a slows the desensitisation kinetics of proton-activated ASIC1a currents across multiple application pHs, and when bound directly to ASIC1a in the desensitised conformation promotes current inhibition. The solution structure of Hc3a was solved, and the peptide-channel interaction examined via mutagenesis studies to highlight how small differences in sequence between Hc3a and PcTx1 can lead to peptides with distinct pharmacology. The discovery of Hc3a expands the pharmacological diversity of spider venom peptides targeting ASIC1a and adds to the toolbox of compounds to study the intricacies of ASIC1 gating.

Role of the complement system in kidney cell death induced by Loxosceles venom Sphingomyelinases D.

Envenomation by Loxosceles spiders can result in local and systemic pathologies. Systemic loxoscelism, which can lead to death, is characterized by intravascular hemolysis, platelet aggregation, and acute kidney injury. Sphingomyelinase D (SMase D) in Loxosceles spider venom is responsible for both local and systemic pathologies, and has been shown to induce metalloprotease activity. As the complement system is involved in many renal pathologies and is involved in hemolysis in systemic loxoscelism, the aim of this study was to investigate its role and the role of complement regulators and metalloproteases in an in vitro model of Loxosceles venom induced renal pathology. We investigated the effects of the venom/SMase D and the complement system on the HK-2 kidney cell line. Using cell viability assays, western blotting, and flow cytometry, we show that human serum, as a source of complement, enhanced the venom/SMase D induced cell death and the deposition of complement components and properdin. Inhibitors for ADAM-10 and ADAM-17 prevented the venom induced release of the of the complement regulator MCP/CD46 and reduced the venom/SMase D induced cell death. Our results show that the complement system can contribute to Loxosceles venom induced renal pathology. We therefore suggest that patients experiencing systemic loxoscelism may benefit from treatment with metalloproteinase inhibitors and complement inhibitors, but this proposition should be further analyzed in future pre-clinical and clinical assays.

The Synthetic Peptide LyeTx I mn∆K, Derived from Lycosa erythrognatha Spider Toxin, Is Active against Methicillin-Resistant Staphylococcus aureus (MRSA) In Vitro and In Vivo.

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8-16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.

The synthetic peptide, PnPP-15, derived from the PnTx2-6 toxin of the spider Phoneutria nigriventer, induces peripheral antinociception involving neprilysin, opioid, and cannabinoid systems

BackgroundThe PnTx2–6 toxin is isolated from the Phoneutria nigriventer spider venom. The synthetic peptide PnPP-19 is derived from this toxin and induces antinociception. When topically applied, it is cleaved by proteases generating a 15 amino acid residues peptide, PnPP-15. PnPP-15 showed an antinociceptive effect in neuropathic pain developed by streptozotocin-induced diabetic mice. The present work aimed to investigate if PnPP-15 is also effective against the inflammatory pain induced by PGE2. We also evaluated its cytotoxicity in vitro and studied its possible action mechanism in the pain pathway. MethodsThe nociceptive threshold was assessed using the mechanical paw pressure test. Paw tissue was collected for protein extraction and western blot analyses. The FRET enzymatic assay measured neprilysin activity. The two-electrode voltage clamp technique measured evoked electrical currents in Xenopus laevis oocytes. Cytotoxicity was measured using multiple cell lines. ResultsPnPP-15 has peripheral antinociceptive activity via µ-opioid and CB1 cannabinoid receptors and inhibits neprilysin. In addition, it induced direct activation of mu-opioid receptors expressed in Xenopus laevis oocytes. PnPP-15 was not cytotoxic against mammalian kidney, liver, heart, nerve, or lung cells. ConclusionThis work demonstrated the antinociceptive effect of PnPP-15 in an inflammatory pain model, suggesting its use as a possible tool for developing new analgesic drugs.