Pharmacological characterization of cnidarian extracts from the Caribbean Sea: evaluation of anti-snake venom and antitumor properties

Background: Cnidarians produce toxins, which are composed of different polypeptides that induce pharmacological effects of biotechnological interest, such as antitumor, antiophidic and anti-clotting activities. This study aimed to evaluate toxicological activities and potential as antitumor and antiophidic agents contained in total extracts from five cnidarians: Millepora alcicornis, Stichodactyla helianthus, Plexaura homomalla, Bartholomea annulata and Condylactis gigantea (total and body wall). Methods: The cnidarian extracts were evaluated by electrophoresis and for their phospholipase, proteolytic, hemorrhagic, coagulant, fibrinogenolytic, neuromuscular blocking, muscle-damaging, edema-inducing and cytotoxic activities. Results: All cnidarian extracts showed indirect hemolytic activity, but only S. helianthus induced direct hemolysis and neurotoxic effect. However, the hydrolysis of NBD-PC, a PLA2 substrate, was presented only by the C gigantea (body wall) and S. helianthus. The extracts from P. homomalla and S. helianthus induced edema, while only C gigantea and S. helianthus showed intensified myotoxic activity. The proteolytic activity upon casein and fibrinogen was presented mainly by B. annulata extract and all were unable to induce hemorrhage or fibrinogen coagulation. Cnidarian extracts were able to neutralize clotting induced by Bothrops jararacussu snake venom, except M. alcicornis. All cnidarian extracts were able to inhibit hemorrhagic activity induced by Bothrops moojeni venom. Only the C. gigantea (body wall) inhibited thrombin-induced coagulation. All cnidarian extracts showed antitumor effect against Jurkat cells, of which C. gigantea (body wall) and S. helianthus were the most active; however, only C. gigantea (body wall) and M. alcicornis were active against B16F10 cells...(AU)

Pharmacological characterization of cnidarian extracts from the Caribbean Sea: evaluation of anti-snake venom and antitumor properties

Background: Cnidarians produce toxins, which are composed of different polypeptides that induce pharmacological effects of biotechnological interest, such as antitumor, antiophidic and anti-clotting activities. This study aimed to evaluate toxicological activities and potential as antitumor and antiophidic agents contained in total extracts from five cnidarians: Millepora alcicornis, Stichodactyla helianthus, Plexaura homomalla, Bartholomea annulata and Condylactis gigantea (total and body wall). Methods: The cnidarian extracts were evaluated by electrophoresis and for their phospholipase, proteolytic, hemorrhagic, coagulant, fibrinogenolytic, neuromuscular blocking, muscle-damaging, edema-inducing and cytotoxic activities. Results: All cnidarian extracts showed indirect hemolytic activity, but only S. helianthus induced direct hemolysis and neurotoxic effect. However, the hydrolysis of NBD-PC, a PLA2 substrate, was presented only by the C gigantea (body wall) and S. helianthus. The extracts from P. homomalla and S. helianthus induced edema, while only C gigantea and S. helianthus showed intensified myotoxic activity. The proteolytic activity upon casein and fibrinogen was presented mainly by B. annulata extract and all were unable to induce hemorrhage or fibrinogen coagulation. Cnidarian extracts were able to neutralize clotting induced by Bothrops jararacussu snake venom, except M. alcicornis. All cnidarian extracts were able to inhibit hemorrhagic activity induced by Bothrops moojeni venom. Only the C. gigantea (body wall) inhibited thrombin-induced coagulation. All cnidarian extracts showed antitumor effect against Jurkat cells, of which C. gigantea (body wall) and S. helianthus were the most active; however, only C. gigantea (body wall) and M. alcicornis were active against B16F10 cells...

Experimental Lachesis muta rhombeata envenomation and effects of soursop (Annona muricata) as natural antivenom

In the Atlantic forest of the North and Northeast regions of Brazil, local population often uses the fruit juice and the aqueous extract of leaves of soursop (Annona muricata L.) to treat Lachesis muta rhombeata envenomation. Envenomation is a relevant health issue in these areas, especially due to its severity and because the production and distribution of antivenom is limited in these regions. The aim of the present study was to evaluate the relevance of the use of soursop leaf extract and its juice against envenomation by Lachesis muta rhombeata. Methods We evaluated the biochemical, hematological and hemostatic parameters, the blood pressure, the inflammation process and the lethality induced by Lachesis muta rhombeata snake venom. We also assessed the action of the aqueous extract of leaves (AmL) and juice (AmJ) from A. muricata on the animal organism injected with L. m. rhombeata venom (LmrV) in the laboratory environment. Results LmrV induced a decrease of total protein, albumin and glucose; and increase of creatine kinase, aspartate aminotransferase, and urea concentrations. It provoked hemoconcentration followed by reduction of hematocrit, an increase in prothrombin time and partial thromboplastin time and a decrease of the blood pressure. LmrV induced the release of interleukin-6, an increase in neutrophils and changes in the serum protein profile, characteristic of the acute inflammatory process. LD50 values were similar for the groups injected with LmrV and treated or untreated with AmJ and AmL. Both treatments play a role on the maintenance of blood glucose, urea and coagulation parameters and exert a protective action against the myotoxicity. However, they seem to worsen the hypotension caused by LmrV. Conclusion The treatments with AmJ and AmL present some beneficial actions, but they might intensify some effects of the venom. Therefore, additional studies on A. muricata are necessary to enable its use as natural antivenom for bushmaster snakebite.(AU)

Experimental Lachesis muta rhombeata envenomation and effects of soursop (Annona muricata) as natural antivenom

In the Atlantic forest of the North and Northeast regions of Brazil, local population often uses the fruit juice and the aqueous extract of leaves of soursop (Annona muricata L.) to treat Lachesis muta rhombeata envenomation. Envenomation is a relevant health issue in these areas, especially due to its severity and because the production and distribution of antivenom is limited in these regions. The aim of the present study was to evaluate the relevance of the use of soursop leaf extract and its juice against envenomation by Lachesis muta rhombeata. Methods We evaluated the biochemical, hematological and hemostatic parameters, the blood pressure, the inflammation process and the lethality induced by Lachesis muta rhombeata snake venom. We also assessed the action of the aqueous extract of leaves (AmL) and juice (AmJ) from A. muricata on the animal organism injected with L. m. rhombeata venom (LmrV) in the laboratory environment. Results LmrV induced a decrease of total protein, albumin and glucose; and increase of creatine kinase, aspartate aminotransferase, and urea concentrations. It provoked hemoconcentration followed by reduction of hematocrit, an increase in prothrombin time and partial thromboplastin time and a decrease of the blood pressure. LmrV induced the release of interleukin-6, an increase in neutrophils and changes in the serum protein profile, characteristic of the acute inflammatory process. LD50 values were similar for the groups injected with LmrV and treated or untreated with AmJ and AmL. Both treatments play a role on the maintenance of blood glucose, urea and coagulation parameters and exert a protective action against the myotoxicity. However, they seem to worsen the hypotension caused by LmrV. Conclusion The treatments with AmJ and AmL present some beneficial actions, but they might intensify some effects of the venom. Therefore, additional studies on A. muricata are necessary to enable its use as natural antivenom for bushmaster snakebite.

Experimental Lachesis muta rhombeata envenomation and effects of soursop (Annona muricata) as natural antivenom

Background In the Atlantic forest of the North and Northeast regions of Brazil, local population often uses the fruit juice and the aqueous extract of leaves of soursop (Annona muricata L.) to treat Lachesis muta rhombeata envenomation. Envenomation is a relevant health issue in these areas, especially due to its severity and because the production and distribution of antivenom is limited in these regions. The aim of the present study was to evaluate the relevance of the use of soursop leaf extract and its juice against envenomation by Lachesis muta rhombeata. Methods We evaluated the biochemical, hematological and hemostatic parameters, the blood pressure, the inflammation process and the lethality induced by Lachesis muta rhombeata snake venom. We also assessed the action of the aqueous extract of leaves (AmL) and juice (AmJ) from A. muricata on the animal organism injected with L. m. rhombeata venom (LmrV) in the laboratory environment. Results LmrV induced a decrease of total protein, albumin and glucose; and increase of creatine kinase, aspartate aminotransferase, and urea concentrations. It provoked hemoconcentration followed by reduction of hematocrit, an increase in prothrombin time and partial thromboplastin time and a decrease of the blood pressure. LmrV induced the release of interleukin-6, an increase in neutrophils and changes in the serum protein profile, characteristic of the acute inflammatory process. LD50 values were similar for the groups injected with LmrV and treated or untreated with AmJ and AmL. Both treatments play a role on the maintenance of blood glucose, urea and coagulation parameters and exert a protective action against the myotoxicity. However, they seem to worsen the hypotension caused by LmrV. Conclusion The treatments with AmJ and AmL present some beneficial actions, but they might intensify some effects of the venom. Therefore, additional studies on A. muricata are necessary to enable its use as natural antivenom for bushmaster snakebite.(AU)

PERFIL HEMATOLÓGICO, BIOQUÍMICO, URINÁRIO E ULTRASSONOGRÁFICO DE EQUINOS SUBMETIDOS À INOCULAÇÃO DO VENENO CROTÁLICO

Os acidentes ofídicos representam um problema de saúde pública nos países tropicais devido à alta incidência e morbimortalidade. No tratamento é utilizado infusão do soro antiofídico que é produzido a partir da hiperimunização de cavalos com a mistura de venenos característicos da região. O objetivo desta pesquisa foi avaliar a função hepática e renal dos equinos submetidos à produção do soro antiofídico com o protocolo de imunização empregado pelo Instituto Vital Brazil (IVB), para um melhor entendimento da resposta imune do equino, visando protocolos que minimizem os efeitos deletérios à saúde dos mesmos. O estudo foi realizado na fazenda do IVB durante o ano de 2019.Os animais foram examinados antes do início dos protocolos para o grupo controle. Depois foram realizados exames hematológicos e perfil bioquímico até 48hs após a inoculação do veneno e semanalmente, avaliação ultrassonográfica hepática e renal até 48hs após a inoculação do veneno e a cada 15 dias, exames de urinálise a cada 15 dias e avaliação clínica dos animais semanalmente após a inoculação do veneno. Os exames foram separados em quatro grupos de acordo com os protocolos de inoculação do veneno: C (grupo controle), IB (imunização de base), PR (primeira reimunização) e SR (segunda reimunização). Foram encontradas diferenças estatísticas nas variáveis hematimetria, hemoglobina, VG, VGM, CHGM, proteína, fibrinogênio, segmentado e linfócito no perfil hematológico; nas variáveis: ureia, creatinina, GGT, albumina e globulina no perfil bioquímico; e nas variáveis: proteína, pH e na relação proteína: creatinina na urinálise. No exame ultrassonográfico do fígado foi encontrada diferença na variável dimensão e no rim nas variáveis: relação córticomedular, ecogenicidade e espessura da cortical. Concluímos que a função hepática e renal dos equinos foi afetada pela inoculação do veneno crotálico. Desta forma devemos ponderar a utilização de suplementações e medicações que minimizem o processo inflamatório e anêmico estabelecido nos equinos inoculados com o veneno. E sugerimos mais pesquisas relacionadas ao assunto para proporcionar bem-estar aos animais submetidos ao processo de inoculação do veneno, que é uma etapa primordial para a produção dos soros antiofídicos.

Ophidian accidents represent a public health problem in tropical countries due to the high incidence and morbimortality. An infusion of antiophidic serum is used for treatment, which is produced from the hyperimmunization of equines with a mixture of poisons characteristic of the region. The objective of this research was to evaluate liver and kidney function of equines submitted to production of antiophidic serum with immunization protocol used by Vital Brazil Institute (IVB), as we expect a better understanding on immune response of equines, aiming at protocols that minimize deleterious effects on their health. The study was carried out at IVB farm during 2019. Animals were examined before start of protocols for the control group. Complete Blood Count (CBC) and biochemistry profile, hepatic and renal ultrasound evaluation, urinalysis and clinical evaluation of the animals were performed up to 48 hours after inoculation of the venom, weekly (in the case of CBC, biochemistry profile and clinical evaluation) and every 15 days. (in the case of urinalysis and ultrasound exams).The exams were separated into four groups according to venom inoculation protocols: C (control group), IB (basic immunization), PR (first re-immunization) and SR (second re-immunization). Statistical differences were found in variables erythrocyte, hemoglobin, corpuscular volume (CV), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), protein, fibrinogen, segmented neutrophils and lymphocyte in CBC results; in urea, creatinine, GGT, albumin and globulin in the biochemistry profile; and in protein, pH, protein:creatinine ratio in urinalysis. In the hepatic ultrasound examination, a difference was found in variable dimension and in the kidneys in variables: corticomedullary ratio, echogenicity and cortical thickness. We conclude that liver and kidney function was affected in equines submitted to crotalic venom inoculation. Thus, we must consider the use of supplements and drugs that minimize the inflammatory and anemic process established in equines inoculated with the venom. And we suggest more research related to this matter to provide welfare to animals submitted to poison inoculation process, which is a primordial step for antiophidic serum production.