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Crotalus neutralizing factor (CNF) is an endogenous glycoprotein from Crotalus durissus terrificus snake blood that inhibits secretory phospholipases A2 (sPLA2) from the Viperid but not from Elapid venoms (subgroups IA and IIA, respectively). In the present study, we demonstrated that CNF can inhibit group III-PLA2 from bee venom by forming a stable enzyme-inhibitor complex. This finding opens up new possibilities for the potential use of CNF and/or CNF-based derivatives in the therapeutics of bee stings.

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Bee stings (BS) are a life-threatening issue and a growing concern for public health and animals in the Americas. We describe the clinical, pathological, and ultrastructural findings of a massive lethal bee attack in two non-human primates (NHPs). Both animals showed BS scattered throughout the skin, surrounded by a local reaction, diffuse pulmonary congestion, edema, hemorrhage, and remarkable degeneration and necrosis of renal epithelial cells from the proximal and distal tubules, characterizing a systemic bee envenomation reaction.

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The therapeutic potential of bee venom-derived peptides, particularly apamin and melittin, in cancer treatment has garnered significant attention as a promising avenue for advancing oncology. This systematic review examines preclinical studies highlighting the emerging role of these peptides in enhancing cancer therapies. Melittin and apamin, when conjugated with other therapeutic agents or formulated into novel delivery systems, have demonstrated improved efficacy in targeting tumor cells. Key findings indicate that melittin-based conjugates, such as polyethylene glycol (PEG)ylated versions, show potential in enhancing therapeutic outcomes and minimizing toxicity across various cancer models. Similarly, apamin-conjugated formulations have improved the efficacy of established anti-cancer drugs, contributing to enhanced targeting and reduced systemic toxicity. These developments underscore a growing interest in leveraging bee venom-derived peptides as adjuncts in cancer therapy. The integration of these peptides into treatment regimens offers a promising strategy to address current limitations in cancer treatment, such as drug resistance and off-target effects. However, comprehensive validation through clinical trials is essential to confirm their safety and effectiveness in human patients. This review highlights the global emergence of bee venom-derived peptides in cancer treatment, advocating for continued research and development to fully realize their therapeutic potential.

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This study evaluated the neuroprotective effects of the Africanized bee venom (BV) and its mechanisms of action after 6-hydroxydopamine-(6-OHDA)-induced lesion in a mice model. Prior to BV treatment, mice received intrastriatal microinjections of 6-OHDA (no induced dopaminergic neuronal death) or ascorbate saline (as a control). BV was administered subcutaneously at different dosages (0.01, 0.05 or 0.1 mg·Kg-1) once every two days over a period of 3 weeks. The open field test was carried out, together with the immunohistochemical and histopathological analysis. The chemical composition of BV was also assessed, identifying the highest concentrations of apamin, phospholipase A2 and melittin. In the behavioral evaluation, the BV (0.1 mg·Kg-1) counteracted the 6-OHDA-induced decrease in crossings and rearing. 6-OHDA caused loss of dopaminergic cell bodies in the substantia nigra pars compacta and fibers in striatum (STR). Mice that received 0.01 mg·Kg-1 showed significant increase in the mean survival of dopaminergic cell bodies. Increased astrocytic infiltration occurred in the STR of 6-OHDA injected mice, differently from those of the groups treated with BV. The results suggested that Africanized BV has neuroprotective activity in an animal model of Parkinson's disease.

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Bees are one of the ancient and the most social insects worldwide. They are of great economic and medical importance. Bee venom (BV) has many therapeutic effects and has been used since ancient times for the treatment of many diseases. The present study aimed to evaluate and compare the antibacterial effect of BV from two different bee subspecies Apis mellifera yemenitica (A. m. yemenitica) (indigenous strain) and Apis mellifera carnica (A. m. carnica) (carniolan strain) against selected Gram-positive and Gram-negative bacteria. Experimentally, venoms were extracted using an electrical venom collector from honey bee colonies of the subspecies, A. m. yemenitica and A. m. carnica, in Hail, Saudi Arabia. Each venom was tested against selected medically important Gram-negative strains, Salmonella Typhimurium, Pseudomonas aeruginosa, and Escherichia coli, while Staphylococcus aureus was selected as Gram-positive test organism. The minimum inhibitory concentration (MIC) method was used to compare the effect of BV from the two subspecies on the growth of the selected bacterial strains. Results showed that BV from both subspecies could equally inhibit the growth of Salmonella Typhimurium, Pseudomonas aeruginosa, and Escherichia coli at an MIC of 10 mg/ml. However, S. aureus was inhibited by an MIC of 5 and 10 mg/ml of BV from A. m. carnica and A. m. yemenitica, respectively. This suggested that the BV of the carnica subspecie was more inhibitory to this Gram-positive pathogen than its counterpart produced by the yemenitica subspecies. The present study shows that bee venom has a promising antibacterial effect.

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Background: Melittin has shown antiproliferative effects on tumor cells. Therefore, it comprises a valuable compound for studies on cancer treatment. To the best of our knowledge, no studies have reported melittin effects on bone metastasis. Herein, we propose an approach based on intrametastatic melittin injection to treat bone metastases in colorectal cancer. Methods: Following the characterization of melittin and antiproliferative tests in vitro, a single dose was injected through intrametastatic route into the mouse bone metastasis model. Following treatment, metastasis growth was evaluated. Results: A single dose of melittin was able to inhibit metastasis growth. Histological analysis showed necrosis and inflammatory processes in melittin-treated metastasis. Except by mild weight loss, no other systemic effects were observed. Conclusion: Our data suggest that melittin might be a promising agent for the future development of treatment strategies aiming to reduce the bone metastasis skeletal-related impact in colorectal cancer patients with bone metastasis.

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Epilepsy is a chronic neuropathology characterized by an abnormal hyperactivity of neurons that generate recurrent, spontaneous, paradoxical and synchronized nerve impulses, leading or not to seizures. This neurological disorder affects around 70 million individuals worldwide. Pharmacoresistance is observed in about 30% of the patients and long-term use of antiepileptics may induce serious side effects. Thus, there is an interest in the study of the therapeutic potential of bioactive substances isolated from natural products in the treatment of epilepsy. Arthropod venoms contain neurotoxins that have high affinity for molecular structures in the neural tissue such as receptors, transporters and ion channels both in glial and neuronal membranes. This study evaluated the potential neuroprotective effect of melittin (MEL), an active compound of bee venom, in the bicuculline-induced seizure model (BIC) in rats. Male Wistar rats (3 months, 250-300 g) were submitted to surgery for the implantation of a unilateral cannula in the lateral ventricle. After the recovery period, rats received a microinjection of saline solution or MEL (0.1 mg per animal). Firstly, rats were evaluated in the open field (20 min) and in the elevated plus maze (5 min) tests after received microinjection of saline or MEL. After, 30 min later animals received BIC (100 mg/ml) or saline, and their behaviors were analyzed for 20 min in the open field according to a seizure scale. At the end, rats were euthanized, brains collected and processed to glial fibrillary acidic protein (GFAP) immunohistochemistry evaluation. No changes were observed in MEL-treated rats in the open field and elevated plus maze. However, 90% of MEL-treated animals were protected against seizures induced by BIC. There was an increase in the latency for the onset of seizures, accompanied by a reduction of GFAP-immunoreactivity cells in the dentate gyrus and CA1. Thus, our study suggests that MEL has an anticonvulsant potential, and further studies are needed to elucidate the mechanisms involved in this action.

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Background: Melittin has shown antiproliferative effects on tumor cells. Therefore, it comprises a valuable compound for studies on cancer treatment. To the best of our knowledge, no studies have reported melittin effects on bone metastasis. Herein, we propose an approach based on intrametastatic melittin injection to treat bone metastases in colorectal cancer. Methods: Following the characterization of melittin and antiproliferative tests in vitro, a single dose was injected through intrametastatic route into the mouse bone metastasis model. Following treatment, metastasis growth was evaluated. Results: A single dose of melittin was able to inhibit metastasis growth. Histological analysis showed necrosis and inflammatory processes in melittin-treated metastasis. Except by mild weight loss, no other systemic effects were observed. Conclusion: Our data suggest that melittin might be a promising agent for the future development of treatment strategies aiming to reduce the bone metastasis skeletal-related impact in colorectal cancer patients with bone metastasis.(AU)

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Abstract Background: Melittin has shown antiproliferative effects on tumor cells. Therefore, it comprises a valuable compound for studies on cancer treatment. To the best of our knowledge, no studies have reported melittin effects on bone metastasis. Herein, we propose an approach based on intrametastatic melittin injection to treat bone metastases in colorectal cancer. Methods: Following the characterization of melittin and antiproliferative tests in vitro, a single dose was injected through intrametastatic route into the mouse bone metastasis model. Following treatment, metastasis growth was evaluated. Results: A single dose of melittin was able to inhibit metastasis growth. Histological analysis showed necrosis and inflammatory processes in melittin-treated metastasis. Except by mild weight loss, no other systemic effects were observed. Conclusion: Our data suggest that melittin might be a promising agent for the future development of treatment strategies aiming to reduce the bone metastasis skeletal-related impact in colorectal cancer patients with bone metastasis.

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In this study, the toxic effects of melittin on Madin-Darby Bovine Kidney cells (MDBK) were analyzed with respect to mitochondrial functionality by reduction of MTT and flow cytometry, apoptosis potential, necrosis, oxygen reactive species (ROS) production, lipid peroxidation, and DNA fragmentation using flow cytometry and cell membrane destabilization by confocal microscopy. The toxicity presented dose-dependent characteristics and mitochondrial activity was inhibited by up to 78.24 ±3.59% (P<0.01, n = 6) in MDBK cells exposed to melittin (10µg/mL). Flow cytometry analysis revealed that melittin at 2µg/mL had the highest necrosis rate (P<0.05) for the cells. The lipoperoxidation of the membranes was also higher at 2µg/mL of melittin (P<0.05), which was further confirmed by the microphotographs obtained by confocal microscopy. The highest ROS production occurred when the cells were exposed to 2.5µg/mL melittin (P<0.05), and this concentration also increased DNA fragmentation (P<0.05). There was a significative and positive correlation between the lipoperoxidation of membranes with ROS (R=0.4158), mitochondrial functionality (R=0.4149), and apoptosis (R=0.4978). Thus, the oxidative stress generated by melittin culminates in the elevation of intracellular ROS that initiates a cascade of toxic events in MDBK cells.(AU)

Neste estudo, os efeitos tóxicos da melitina em células Madin-Darby Bovine Kidney (MDBK) foram analisados quanto à funcionalidade mitocondrial, por redução de MTT e citometria de fluxo, potencial de apoptose, necrose, produção de espécies reativas de oxigênio (ROS), peroxidação lipídica e fragmentação de DNA, utilizando-se citometria de fluxo e desestabilização da membrana celular, por microscopia confocal. A toxicidade apresentou características dose-dependentes e a atividade mitocondrial foi inibida até 78,24±3,59% (P<0,01, n = 6) em células MDBK expostas à melitina (10µg/mL). Análises por citometria de fluxo revelaram que a melitina a 2µg/mL apresentou o maior índice necrótico celular (P<0,05). A maior lipoperoxidação de membranas também foi na concentração de 2µg/mL de melitina (P<0,05), o que foi posteriormente confirmado por microscopia confocal. A maior produção de ROS aconteceu quando as células foram expostas a 2,5µg/mL de melitina (P<0,05), e essa concentração também aumentou a fragmentação de DNA (P<0,05). Houve uma significativa correlação positiva entre a lipoperoxidação de membranas e a produção de ROS (R=0,4158), funcionalidade mitocondrial (R=0,4149) e apoptose (R=0,4978). Portanto, o estresse oxidativo gerado pela melitina culminou na elevação de ROS intracelular, que inicia uma cascata de eventos tóxicos nas células MDBK.(AU)

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The emergence of novel coronavirus (SARS-CoV-2) in 2019 in China marked the third outbreak of a highly pathogenic coronavirus infecting humans. The novel coronavirus disease (COVID-19) spread worldwide, becoming an emergency of major international concern. However, even after a decade of coronavirus research, there are still no licensed vaccines or therapeutic agents to treat the coronavirus infection. In this context, apitherapy presents as a promising source of pharmacological and nutraceutical agents for the treatment and/or prophylaxis of COVID-19. For instance, several honeybee products, such as honey, pollen, propolis, royal jelly, beeswax, and bee venom, have shown potent antiviral activity against pathogens that cause severe respiratory syndromes, including those caused by human coronaviruses. In addition, the benefits of these natural products to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells, and stimulation of the innate and adaptive immune responses. Thus, in the absence of specific antivirals against SARS-CoV-2, apitherapy could offer one hope toward mitigating some of the risks associated with COVID-19.

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ABSTRACT: The objective was to evaluate the in vitro antioxidant, genotoxic, antigenotoxic, and antineoplastic activities of apitoxin produced by the bee Apis mellifera. The antioxidant activity of the apitoxin solution was evaluated using the DPPH (2,2-diphenyl-1-picrilhydrazyl) method. Genotoxic potential of apitoxin was analyzed by comparing the mean DNA damage indices (idDNA) of L929 strain fibroblasts exposed to hydrogen peroxide (H2O2 - genotoxic substance), distilled water, or apitoxin. The antigenotoxic effect of apitoxin was analyzed by assessing the percentage decrease in H2O2-induced genotoxicity in L929 fibroblasts co-treated with three concentrations of the aqueous apitoxin solution and subjected to comet assay. In vitro antineoplastic activity in human tumor cell lines of prostate adenocarcinoma (PC3), hepatocellular carcinoma (HEPGE2), melanoma (MAD-MB435), and astrocytoma (SNB19), were verified by MTT [3- (4) bromide colorimetric method, 5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium]. Apitoxin had no genotoxic effect on L929 cells at concentrations of 30, 10, and 5 µg/mL after 24 hours of exposure. This effect was only evident at 50 µg/mL. Apitoxin promoted a significant reduction in DNA damage index (idDNA) at all concentrations tested. At 30 µg/mL, apitoxin attenuated the genotoxic effects induced by H2O2. Apitoxin also demonstrated in vitro antineoplastic potential, since the cytotoxic effect was observed at concentrations of 50 µg/mL and 25 µg/mL, with significant reduction in viability percentage of PC3 tumor cell lines, HEPGE2, MAD-MB435, and SNB19. The high antioxidant activity associated with the absence of genotoxic effect and the genoprotective and antineoplastic effect demonstrated by apitoxin here provide indications of apitoxin's therapeutic potential.

RESUMO: O objetivo deste estudo foi avaliar as atividades antioxidantes, genotóxicas, antigenotóxicas e antineoplásicas in vitro da apitoxina produzida pela abelha Apis mellifera. A atividade antioxidante da solução da apitoxina foi avaliada pelo método DPPH (2,2-difenil-1-picrilhidrazil). O potencial genotóxico da apitoxina foi analisado através dos índices médios de dano ao DNA (idDNA) dos fibroblastos da linhagem L929 expostos à peróxido de hidrogênio (H2O2 - substância genotóxica), água destilada ou apitoxina. O efeito antigenotóxico da apitoxina foi analisado através da avaliação da diminuição percentual na genotoxicidade induzida por H2O2 nos fibroblastos L929 co-tratados com três concentrações da solução aquosa de apitoxina e submetidos ao ensaio cometa. A atividade antineoplásica in vitro em linhagens celulares tumorais humanas de adenocarcinoma da próstata (PC3), carcinoma hepatocelular (HEPGE2), melanoma (MAD-MB435) e astrocitoma (SNB19), foram verificadas pelo método colorimétrico do brometo de MTT [3- (4), 5-dimetiltiazol -2-il) -2,5-difeniltetrazólio]. A apitoxina não teve efeito genotóxico nas células L929 nas concentrações de 30, 10 e 5 µg / mL após 24 horas de exposição. Este efeito foi apenas evidente a 50 µg / mL. A apitoxina promoveu uma redução significativa no índice de danos ao DNA (idDNA) em todas as concentrações testadas. A 30 µg / mL, a apitoxina atenuou os efeitos genotóxicos induzidos por H2O2. A apitoxina também demonstrou potencial antineoplásico in vitro, uma vez que o efeito citotóxico foi observado em concentrações de 50 µg / mL e 25 µg / mL, com redução significativa na porcentagem de viabilidade das linhagens celulares de PC3, HEPGE2, MAD-MB435 e SNB19. A alta atividade antioxidante associada à ausência de efeito genotóxico e o efeito genoprotetor e antineoplásico demonstrado pela apitoxina aqui fornecem indicações do potencial terapêutico da apitoxina.

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The objective was to evaluate the in vitro antioxidant, genotoxic, antigenotoxic, and antineoplastic activities of apitoxin produced by the bee Apis mellifera. The antioxidant activity of the apitoxin solution was evaluated using the DPPH (2,2-diphenyl-1-picrilhydrazyl) method. Genotoxic potential of apitoxin was analyzed by comparing the mean DNA damage indices (idDNA) of L929 strain fibroblasts exposed to hydrogen peroxide (H2O2 - genotoxic substance), distilled water, or apitoxin. The antigenotoxic effect of apitoxin was analyzed by assessing the percentage decrease in H2O2-induced genotoxicity in L929 fibroblasts co-treated with three concentrations of the aqueous apitoxin solution and subjected to comet assay. In vitro antineoplastic activity in human tumor cell lines of prostate adenocarcinoma (PC3), hepatocellular carcinoma (HEPGE2), melanoma (MAD-MB435), and astrocytoma (SNB19), were verified by MTT [3- (4) bromide colorimetric method, 5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium]. Apitoxin had no genotoxic effect on L929 cells at concentrations of 30, 10, and 5 µg/mL after 24 hours of exposure. This effect was only evident at 50 µg/mL. Apitoxin promoted a significant reduction in DNA damage index (idDNA) at all concentrations tested. At 30 µg/mL, apitoxin attenuated the genotoxic effects induced by H2O2. Apitoxin also demonstrated in vitro antineoplastic potential, since the cytotoxic effect was observed at concentrations of 50 µg/mL and 25 µg/mL, with significant reduction in viability percentage of PC3 tumor cell lines, HEPGE2, MAD-MB435, and SNB19. The high antioxidant activity associated with the absence of genotoxic effect and the genoprotective and antineoplastic effect demonstrated by apitoxin here provide indications of apitoxins therapeutic potential.(AU)

O objetivo deste estudo foi avaliar as atividades antioxidantes, genotóxicas, antigenotóxicas e antineoplásicas in vitro da apitoxina produzida pela abelha Apis mellifera. A atividade antioxidante da solução da apitoxina foi avaliada pelo método DPPH (2,2-difenil-1-picrilhidrazil). O potencial genotóxico da apitoxina foi analisado através dos índices médios de dano ao DNA (idDNA) dos fibroblastos da linhagem L929 expostos à peróxido de hidrogênio (H2O2 - substância genotóxica), água destilada ou apitoxina. O efeito antigenotóxico da apitoxina foi analisado através da avaliação da diminuição percentual na genotoxicidade induzida por H2O2 nos fibroblastos L929 co-tratados com três concentrações da solução aquosa de apitoxina e submetidos ao ensaio cometa. A atividade antineoplásica in vitro em linhagens celulares tumorais humanas de adenocarcinoma da próstata (PC3), carcinoma hepatocelular (HEPGE2), melanoma (MAD-MB435) e astrocitoma (SNB19), foram verificadas pelo método colorimétrico do brometo de MTT [3- (4), 5-dimetiltiazol -2-il) -2,5-difeniltetrazólio]. A apitoxina não teve efeito genotóxico nas células L929 nas concentrações de 30, 10 e 5 µg / mL após 24 horas de exposição. Este efeito foi apenas evidente a 50 µg / mL. A apitoxina promoveu uma redução significativa no índice de danos ao DNA (idDNA) em todas as concentrações testadas. A 30 µg / mL, a apitoxina atenuou os efeitos genotóxicos induzidos por H2O2. A apitoxina também demonstrou potencial antineoplásico in vitro, uma vez que o efeito citotóxico foi observado em concentrações de 50 µg / mL e 25 µg / mL, com redução significativa na porcentagem de viabilidade das linhagens celulares de PC3, HEPGE2, MAD-MB435 e SNB19. A alta atividade antioxidante associada à ausência de efeito genotóxico e o efeito genoprotetor e antineoplásico demonstrado pela apitoxina aqui fornecem indicações do potencial terapêutico da apitoxina.(AU)

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Introduction: Bee venom (BV) allergy, a common cause of anaphylaxis in adults, is often associated with severe reactions. The use of component-resolved diagnostics (CRD) increases diagnostic accuracy. Objectives: To characterize the sensitization profile of BV allergic patients and a possible correlation with the severity of reaction. Materials and methods: We selected patients with a clinical history of BV allergy, positive skin tests, and specific IgE (sIgE) for BV. The allergenic profile was analyzed by both CRD and Western blot using a well-defined and properly characterized BV extract. Results: Forty-four patients were included, 30 (68.2%) were men. Mean age was 48.9 (SD 17.9) years. Eleven (25%) had large local reactions (LLRs) and 33 (75%) had systemic sting reactions (SSRs). One patient with negative sIgE for BV had positive sIgE for Api m 1, Api m 5, and Api m 10. The sensitization frequency for BV, Api m 1, Api m 2, Api m 3, Api m 5, and Api m 10 was 97.7%, 75%, 47.7%, 20.5%, 40.9%, and 61.4%, respectively. Five patients (11.4%) were sensitized to all BV components. CRD association showed that 5 patients (11.4%) were sensitized only to Api m 1, 8 (18.2%) to Api m 1/Api m 3/Api m 10, and 16 (36.6%) to Api m 1/ Api m 10. Twenty-eight patients (84.8%) with SSRs were sensitized to Api m 1, and concomitant sensitization to Api m 1/Api m 10 was detected in 20 (60.6%). There was a significant difference in Api m 1 between patients with LLRs and SSRs (p = 0.0104). Similar profiles were identified by Western blot analysis, with relevance for the detection of Api m 6 in 28 (64%) and Api m 4 in 16 (36%) patients. Conclusion: The analysis of the sensitization profile using CRD and the association of several of these components can increase diagnostic accuracy in BV allergy. Our data showed that concomitant sensitization to Api m 1 and Api m 10, detected by both CRD and electrophoretic profile, may be associated with SSRs. We emphasize the identification of sensitization to Api m 6 in > 50% of patients, which may be considered a major allergen, and to Api m 4, which may be related to reactions during BV immunotherapy.

Introdução: A alergia ao veneno de abelha (VA) é uma causa frequente de anafilaxia em adultos e está muitas vezes associada a reações graves. O diagnóstico por componentes moleculares (CRD) contribui para uma melhor caracterização desta alergia. Objetivos: Caracterização do perfil de sensibilização molecular de doentes alérgicos ao veneno de abelha e possível correlação com a gravidade da reação. Material e métodos: Selecionaram-se doentes com história de alergia a VA, testes cutâneos e IgE específica (sIgE) positivos para VA. Avaliou-se o perfil alergênico por CRD e por Western Blot, utilizando extrato de VA bem caracterizado. Resultados: 44 doentes, 30 (68,2%) sexo masculino. Média de idades 48,9 ± 17,9 anos, 11 (25%) com reacções locais exuberantes e 33 (75%) com reações sistêmicas à picada (SSR). Um doente tinha sIgE negativa para VA, mas Api m 1, Api m 5 e Api m 10 positivas. A frequência de sensibilização para VA, Api m 1, Api m 2, Api m 3, Api m 5 e Api m 10 foi 97,7%; 75%; 47,7%; 20,5%; 40,9% e 61,4%, respectivamente. Cinco (11,4%) doentes estavam sensibilizados a todos os componentes. Por associação de CRD, detectaram-se 5 (11,4%) doentes sensibilizados apenas a Api m 1, 8 (18,2%) a Api m 1/Api m 3/Api m 10, e 16 (36,6%) a Api m 1/Api m 10. Vinte e oito (84,8%) doentes com SSR tinham Api m 1 positiva e 20 (60,6%) tinham Api m 1/Api m 10 simultaneamente positivas. Observou-se uma diferença estatisticamente significativa para a Api m 1 entre doentes com reações locais exuberantes e sistêmicas (p = 0,0104). Os perfis detectados por Western Blot foram semelhantes, de referir, à detecção de Api m 6 em 28 (64%) e Api m 4 em 16 (36%) dos doentes. Conclusão: A análise do perfil de sensibilização através de CRD e a sua associação aumentam a precisão do diagnóstico de alergia a VA. Sensibilização simultânea a Api m 1 e Api m 10 identificados tanto por CRD como por perfil eletroforético, pode estar associada à ocorrência de SSR. Destaca-se a sensibilização a Api m 6 em > 50% dos doentes, podendo ser considerado um alergênio major, e a Api m 4, possivelmente associado a reações durante a imunoterapia com VA.

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Honey bees can be found all around the world and fulfill key pollination roles within their natural ecosystems, as well as in agriculture. Most species are typically docile, and most interactions between humans and bees are unproblematic, despite their ability to inject a complex venom into their victims as a defensive mechanism. Nevertheless, incidences of bee stings have been on the rise since the accidental release of Africanized bees to Brazil in 1956 and their subsequent spread across the Americas. These bee hybrids are more aggressive and are prone to attack, presenting a significant healthcare burden to the countries they have colonized. To date, treatment of such stings typically focuses on controlling potential allergic reactions, as no specific antivenoms against bee venom currently exist. Researchers have investigated the possibility of developing bee antivenoms, but this has been complicated by the very low immunogenicity of the key bee toxins, which fail to induce a strong antibody response in the immunized animals. However, with current cutting-edge technologies, such as phage display, alongside the rise of monoclonal antibody therapeutics, the development of a recombinant bee antivenom is achievable, and promising results towards this goal have been reported in recent years. Here, current knowledge on the venom biology of Africanized bees and current treatment options against bee envenoming are reviewed. Additionally, recent developments within next-generation bee antivenoms are presented and discussed.

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RESUMO

A busca por alternativa aos fármacos sintéticos têm revelado descobertas no campo da farmacologia e, nesse sentido, melitina e apamina, dois constituintes do veneno de abelhas, foram descritas com várias ações farmacológicas. Este estudo objetivou avaliar in vitro as capacidades antiviral e virucida destes componentes. Para tanto, células MDBK (Madin Darby Bovine Kidney), após verificação das respectivas doses tóxicas por ensaio MTT ((3-(4,5 dimetiltiazol-2yl)-2-5-difenil-2H tetrazolato de bromo), foram cultivadas em microplacas e tratadas com diferentes concentrações de apamina, melitina e sua associação. Esse tratamento ocorreu antes e após a infecção com 0,1 MOI (multiplicidade de infecção) de cepas citopatogênicas de herpesvírus bovino tipo 1 (BoHV-1) cepa Los Angeles e vírus da diarreia viral bovina (BVDV) cepa NADL. Após incubação por 72 horas, 37oC, as células foram submetidas ao ensaio MTT para estimativa da viabilidade celular. Em experimento paralelo, placas que foram submetidas ao mesmo procedimento sofreram ciclo de congelamento e descongelamento das células, para rompimento das mesmas e mensuração dos títulos virais. O ensaio virucida foi realizado incubando-se suspensões de BoHV-1 e BVDV com as soluções de apamina, melitina e associação por 24 horas a 37oC e 22oC. O título viral foi avaliado às 0 horas, 1, 2, 4, 8 e 24 horas de incubação. A concentração citotóxica para 50% das células (CC50) de melitina foi 2,32 μg/ml e apamina não demonstrou toxicidade à maior concentração testada (100μg/ml). Houve efeito antiviral da melitina sobre BoHV-1, especialmente na concentração de 2μg/ml, onde observou-se 85,96% de viabilidade celular quando o tratamento foi realizado antes da infecção e 86,78% de viabilidade quando o tratamento foi realizado após a infecção. Houve ainda redução de 90% das partículas virais de BoHV-1. Em menores concentrações (1 e 1,5μg/ml) de melitina não houve atividade antiviral, pois a viabilidade celular foi baixa, demonstrando efeito citopático do vírus. Na associação das duas substâncias houve queda no título de BVDV e observou-se maior viabilidade celular quando comparados à ação isolada dos composto sobre este vírus. Isso se confirma na atividade virucida, uma vez que houve decréscimo de 90% das partículas virais de BVDV com a associação dos dois compostos do veneno de abelhas. Atuando individualmente, melitina apresentou efeito antiviral e virucida frente ao BoHV-1, zerando seu título em apenas 2 horas a 37oC. Conclui-se que melitina tem ação antiviral e virucida frente ao BoHV-1 e sua associação com apamina potencializou seus efeitos frente ao BVDV.(AU)

The search for an alternative to synthetic drugs have revealed discoveries in the field of pharmacology and, according to melittin and apamin, two components of bee venom which have been described were with various pharmacological actions.This study aimed to evaluate the in vitro antiviral and virucidal capabilities of these components. Therefore, after verification of their toxic doses by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, MDBK cells (Madin Darby Bovine Kidney) have been cultivated in microplates and treated with different concentrations of apamin, melittin and its association. This treatment occurred before and after infection with MOI (multiplicity of infection) 0.1 of cytopathogenic strains of bovine herpesvirus type 1 (BoHV-1) strain Los Angeles and bovine viral diarrhea virus (BVDV) strain NADL. After incubation for 72 hours, 37°C, the cells were submitted to MTT assay to estimate cell viability. In parallel experiments, plates were subjected to the same procedure suffered freezing and thawing cycle the cells to rupture the same and measurement of viral titers. The virucidal assay was performed by incubating suspension of bovine herpesvirus type-1 and BVDV with apamin solutions, melittin and association for 24 hours at 37°C and 22°C. The viral titer was evaluated at 0 hours, 1, 2, 4, 8 and 24 hours of incubation. The cytotoxic concentration to 50% of the cells (CC50) of melittin was 2.32g/mL and apamin did not show toxicity at the greater concentration tested (100μg/mL). There was antiviral effect of melittin on bovine herpesvirus type-1, especially at a concentration of 2μg/mL, where was observed 85.96% cell viability when treatment was performed before the infection and 86.78% viability when the treatment was carried out after infection. There was also a 90% reduction of viral particles of bovine herpesvirus type-1. In lower concentrations (1 and 1.5μg/mL) melittin no antiviral activity because cell viability was low, showing cytopathic effect of the virus. At the association two substances there were a decrease in the title of BVDV and there was higher cell viability when compared to the isolated action of the compounds of this virus. This is confirmed in the virucidal activity, since there was a decrease of 90% of the viral particles of BVDV with the combination of the two compounds of bee venom. Acting individually, melittin showed antiviral effect and virucidal against for BoHV-1, zeroing its title in just 2 hours at 37°C. It is concluded that melittin has antiviral and virucidal action against the BoHV-1 and its association with apamin potentiate its effects against BVDV.(AU)

Assuntos

RESUMO

A busca por alternativa aos fármacos sintéticos têm revelado descobertas no campo da farmacologia e, nesse sentido, melitina e apamina, dois constituintes do veneno de abelhas, foram descritas com várias ações farmacológicas. Este estudo objetivou avaliar in vitro as capacidades antiviral e virucida destes componentes. Para tanto, células MDBK (Madin Darby Bovine Kidney), após verificação das respectivas doses tóxicas por ensaio MTT ((3-(4,5 dimetiltiazol-2yl)-2-5-difenil-2H tetrazolato de bromo), foram cultivadas em microplacas e tratadas com diferentes concentrações de apamina, melitina e sua associação. Esse tratamento ocorreu antes e após a infecção com 0,1 MOI (multiplicidade de infecção) de cepas citopatogênicas de herpesvírus bovino tipo 1 (BoHV-1) cepa Los Angeles e vírus da diarreia viral bovina (BVDV) cepa NADL. Após incubação por 72 horas, 37oC, as células foram submetidas ao ensaio MTT para estimativa da viabilidade celular. Em experimento paralelo, placas que foram submetidas ao mesmo procedimento sofreram ciclo de congelamento e descongelamento das células, para rompimento das mesmas e mensuração dos títulos virais. O ensaio virucida foi realizado incubando-se suspensões de BoHV-1 e BVDV com as soluções de apamina, melitina e associação por 24 horas a 37oC e 22oC. O título viral foi avaliado às 0 horas, 1, 2, 4, 8 e 24 horas de incubação. A concentração citotóxica para 50% das células (CC50) de melitina foi 2,32 μg/ml e apamina não demonstrou toxicidade à maior concentração testada (100μg/ml). Houve efeito antiviral da melitina sobre BoHV-1, especialmente na concentração de 2μg/ml, onde observou-se 85,96% de viabilidade celular quando o tratamento foi realizado antes da infecção e 86,78% de viabilidade quando o tratamento foi realizado após a infecção. Houve ainda redução de 90% das partículas virais de BoHV-1. Em menores concentrações (1 e 1,5μg/ml) de melitina não houve atividade antiviral, pois a viabilidade celular foi baixa, demonstrando...(AU)

The search for an alternative to synthetic drugs have revealed discoveries in the field of pharmacology and, according to melittin and apamin, two components of bee venom which have been described were with various pharmacological actions.This study aimed to evaluate the in vitro antiviral and virucidal capabilities of these components. Therefore, after verification of their toxic doses by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, MDBK cells (Madin Darby Bovine Kidney) have been cultivated in microplates and treated with different concentrations of apamin, melittin and its association. This treatment occurred before and after infection with MOI (multiplicity of infection) 0.1 of cytopathogenic strains of bovine herpesvirus type 1 (BoHV-1) strain Los Angeles and bovine viral diarrhea virus (BVDV) strain NADL. After incubation for 72 hours, 37°C, the cells were submitted to MTT assay to estimate cell viability. In parallel experiments, plates were subjected to the same procedure suffered freezing and thawing cycle the cells to rupture the same and measurement of viral titers. The virucidal assay was performed by incubating suspension of bovine herpesvirus type-1 and BVDV with apamin solutions, melittin and association for 24 hours at 37°C and 22°C. The viral titer was evaluated at 0 hours, 1, 2, 4, 8 and 24 hours of incubation. The cytotoxic concentration to 50% of the cells (CC50) of melittin was 2.32g/mL and apamin did not show toxicity at the greater concentration tested (100μg/mL). There was antiviral effect of melittin on bovine herpesvirus type-1, especially at a concentration of 2μg/mL, where was observed 85.96% cell viability when treatment was performed before the infection and 86.78% viability when the treatment was carried out after infection. There was also a 90% reduction of viral particles of...(AU)

Assuntos

RESUMO

ABSTRACT: The search for an alternative to synthetic drugs have revealed discoveries in the field of pharmacology and, according to melittin and apamin, two components of bee venom which have been described were with various pharmacological actions.This study aimed to evaluate the in vitro antiviral and virucidal capabilities of these components. Therefore, after verification of their toxic doses by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, MDBK cells (Madin Darby Bovine Kidney) have been cultivated in microplates and treated with different concentrations of apamin, melittin and its association. This treatment occurred before and after infection with MOI (multiplicity of infection) 0.1 of cytopathogenic strains of bovine herpesvirus type 1 (BoHV-1) strain Los Angeles and bovine viral diarrhea virus (BVDV) strain NADL. After incubation for 72 hours, 37°C, the cells were submitted to MTT assay to estimate cell viability. In parallel experiments, plates were subjected to the same procedure suffered freezing and thawing cycle the cells to rupture the same and measurement of viral titers. The virucidal assay was performed by incubating suspension of bovine herpesvirus type-1 and BVDV with apamin solutions, melittin and association for 24 hours at 37°C and 22°C. The viral titer was evaluated at 0 hours, 1, 2, 4, 8 and 24 hours of incubation. The cytotoxic concentration to 50% of the cells (CC50) of melittin was 2.32g/mL and apamin did not show toxicity at the greater concentration tested (100g/mL). There was antiviral effect of melittin on bovine herpesvirus type-1, especially at a concentration of 2g/mL, where was observed 85.96% cell viability when treatment was performed before the infection and 86.78% viability when the treatment was carried out after infection. There was also a 90% reduction of viral particles of bovine herpesvirus type-1. In lower concentrations (1 and 1.5g/mL) melittin no antiviral activity because cell viability was low, showing cytopathic effect of the virus. At the association two substances there were a decrease in the title of BVDV and there was higher cell viability when compared to the isolated action of the compounds of this virus. This is confirmed in the virucidal activity, since there was a decrease of 90% of the viral particles of BVDV with the combination of the two compounds of bee venom. Acting individually, melittin showed antiviral effect and virucidal against for BoHV-1, zeroing its title in just 2 hours at 37°C. It is concluded that melittin has antiviral and virucidal action against the BoHV-1 and its association with apamin potentiate its effects against BVDV.

RESUMO: A busca por alternativa aos fármacos sintéticos têm revelado descobertas no campo da farmacologia e, nesse sentido, melitina e apamina, dois constituintes do veneno de abelhas, foram descritas com várias ações farmacológicas. Este estudo objetivou avaliar in vitro as capacidades antiviral e virucida destes componentes. Para tanto, células MDBK (Madin Darby Bovine Kidney), após verificação das respectivas doses tóxicas por ensaio MTT ((3-(4,5 dimetiltiazol-2yl)-2-5-difenil-2H tetrazolato de bromo), foram cultivadas em microplacas e tratadas com diferentes concentrações de apamina, melitina e sua associação. Esse tratamento ocorreu antes e após a infecção com 0,1 MOI (multiplicidade de infecção) de cepas citopatogênicas de herpesvírus bovino tipo 1 (BoHV-1) cepa Los Angeles e vírus da diarreia viral bovina (BVDV) cepa NADL. Após incubação por 72 horas, 37oC, as células foram submetidas ao ensaio MTT para estimativa da viabilidade celular. Em experimento paralelo, placas que foram submetidas ao mesmo procedimento sofreram ciclo de congelamento e descongelamento das células, para rompimento das mesmas e mensuração dos títulos virais. O ensaio virucida foi realizado incubando-se suspensões de BoHV-1 e BVDV com as soluções de apamina, melitina e associação por 24 horas a 37oC e 22oC. O título viral foi avaliado às 0 horas, 1, 2, 4, 8 e 24 horas de incubação. A concentração citotóxica para 50% das células (CC50) de melitina foi 2,32 g/ml e apamina não demonstrou toxicidade à maior concentração testada (100g/ml). Houve efeito antiviral da melitina sobre BoHV-1, especialmente na concentração de 2g/ml, onde observou-se 85,96% de viabilidade celular quando o tratamento foi realizado antes da infecção e 86,78% de viabilidade quando o tratamento foi realizado após a infecção. Houve ainda redução de 90% das partículas virais de BoHV-1. Em menores concentrações (1 e 1,5g/ml) de melitina não houve atividade antiviral, pois a viabilidade celular foi baixa, demonstrando efeito citopático do vírus. Na associação das duas substâncias houve queda no título de BVDV e observou-se maior viabilidade celular quando comparados à ação isolada dos composto sobre este vírus. Isso se confirma na atividade virucida, uma vez que houve decréscimo de 90% das partículas virais de BVDV com a associação dos dois compostos do veneno de abelhas. Atuando individualmente, melitina apresentou efeito antiviral e virucida frente ao BoHV-1, zerando seu título em apenas 2 horas a 37oC. Conclui-se que melitina tem ação antiviral e virucida frente ao BoHV-1 e sua associação com apamina potencializou seus efeitos frente ao BVDV.

RESUMO

Spinal cord injuries (SCIs) initiate a series of molecular and cellular events in which inflammatory responses can lead to major neurological dysfunctions. The present study aims to investigate whether bee venom (BV) acupuncture applied at acupoints ST36 (Zusanli) and GV3 (Yaoyangquan) could minimize locomotor deficits and the magnitude of neural tissue losses, and change the balance between pro- and anti-inflammatory cytokines after an SCI by compression. Wistar rats were subjected to an SCI model by compression in which a 2-French Fogarty embolectomy catheter was inflated in the extradural space. The effects of BV acupuncture, in which 20 µL of BV diluted in saline (0.08 mg/kg) was injected at acupoints GV3 and ST36 [BV(ST36+GV3)-SCI] was compared with BV injected at nonacupoints [BV(NP)-SCI] and with no treatment [group subjected only to SCI (CTL-SCI)]. The BV(ST36+GV3)-SCI group showed a significant improvement in the locomotor performance and a decrease of lesion size compared with the controls. BV acupuncture at the ST36 + GV3 increased the expression of interleukin-10 (anti-inflammatory) at 6 hours and reduced the expression of interleukin-6 (proinflammatory) at 24 hours after SCI compared with the controls. Our results suggest that BV acupuncture can reduce neuroinflammation and induce recovery in the SCI compression model.

Assuntos

RESUMO

Abstract Glioblastoma is the most common malignant brain tumor representing with poor prognosis, therapy resistance and high metastasis rate. Increased expression and activity of matrix metalloproteinase-2, a member of matrix metalloproteinase family proteins, has been reported in many cancers including glioblastoma. Inhibition of matrix metalloproteinase-2 expression has resulted in reduced aggression of glioblastoma tumors in several reports. In the present study, we evaluated effect of bee venom on expression and activity of matrix metalloproteinase-2 as well as potential toxicity and apoptogenic properties of bee venom on glioblastoma cells. Human A172 glioblastoma cells were treated with increasing concentrations of bee venom. Then, cell viability, apoptosis, matrix metalloproteinase-2 expression, and matrix metalloproteinase-2 activity were measured using MMT assay, propidium iodide staining, real time-PCR, and zymography, respectively. The IC50 value of bee venom was 28.5 µg/ml in which it leads to decrease of cell viability and induction of apoptosis. Incubation with bee venom also decreased the expression of matrix metalloproteinase-2 in this cell line (p < 0.05). In zymography, there was a reverse correlation between bee venom concentration and total matrix metalloproteinase-2 activity. Induction of apoptosis as well as inhibition of matrix metalloproteinase-2 activity and expression can be suggested as molecular mechanisms involved in cytotoxic and antimetastatic effects of bee venom against glioblastoma cells.