Cardiorespiratory alterations in rodents experimentally envenomed with Hadruroides lunatus scorpion venom

Abstract Background Hadruroides lunatus is the most abundant scorpion species in the Peruvian central coast, where most of the accidents involving humans are registered. In spite of its prevalence, there are only very few studies on H. lunatus envenomation. The aim of the present study was to analyze the cardiorespiratory alterations caused by H. lunatus envenomation in rodents. Methods Wistar rats injected with H. lunatus scorpion venom were submitted to electrocardiography. After euthanasia, rat lungs were collected and histopathologically analyzed. Mouse cardiomyocytes were used to perform immunofluorescence and calcium transient assays. Data were analyzed by ANOVA or Student’s t-test. The significance level was set at p< 0.05. Results It was observed that H. lunatus venom increased heart rate and caused arrhythmia, thereby impairing the heart functioning. Lungs of envenomed animals showed significant alterations, such as diffuse hemorrhage. In addition, immunofluorescence showed that H. lunatus venom was capable of binding to cardiomyocytes. Furthermore, mouse ventricular cardiomyocytes incubated with H. lunatus venom showed a significant decrease in calcium transient, confirming that H. lunatus venom exerts a toxic effect on heart. Conclusion Our results showed that H. lunatus venom is capable of inducing cardiorespiratory alterations, a typical systemic effect of scorpionism, stressing the importance of medical monitoring in envenomation cases.

Scorpion sting-induced myocardial damage and pulmonary oedema.

A patient with electrocardiographic abnormalities simulating early myocardial infarction after scorpion sting is reported. Pulmonary oedema and congestive heart failure accompanied these electrocardiographic changes. The aetiology of the cardiovascular manifestations in severe scorpion sting is related to the venom effects on the sympathetic nervous system and the adrenal secretion of catecholamines, as well as to the toxic effects of the venom on the myocardium.

Tityus zulianus and Tityus discrepans venoms induced massive autonomic stimulation in mice

Venezuelan scorpion envenomation is a public health problem produced by Tityus discrepans (TD) and Tityus zulianus (TZ) species. Patients-envenomend by TD developed gastrointestinal and pacreatic disorders and scorpion accidents involving TZ are associated with high mortality rate, which showed cardiopulmonary clinical disorders may be associated to the high levels of plasma catecholamines levels. This distinctive clinical output seems to be associated to a toxin repertoire diversity, which has been previously demonstrated. Trying to mimic the human-envenomation, some toxinological studies have been performed using TD and TZ venoms in several biomedels such as mice and anesthetized rams. The purpose of this study was to evaluate, in vivo using biomodels (mice), the role of autonomic nervous system (sympathetic) stimulation producing some of the clinical signs, via the catecholamines release, on the patho-physiology of the TZ and TD induced envenomation. Thus, a clinical signs here reported during a period of 1 hr, after a single intra-peritoneal injection of sub-lethal doses of TZ or TD venom, which are related with diarrhea, diaphoresis, intense salivation, dehydratation, dyspnea and spasticity in hind limbs. However, these animals did not exhibit vomiting, which is the most frequent human-envenomed TD patients. All animals inoculated with (TD or TZ) venoms develped diarrhea being more pronounced in TD group. Diaphoresis, sialorrhea and dehydratation were mainly observed in TD group. Dyspnea and the hind limb spasticity were only developed in TZ mice. These clinical manifestations (diarrhea, sialorrhea, dehydratation and intense salivation) are related to an activation of autonomic nervous system, via an intense release of their related neurotransmitters. Thus, autonomic stimulation (sympathetic) was evaluated following the catecholamine (Nor-Epinephrine) (NE) plasma levels in a function of envenomation time. We found a significant increments at 1 hr,...

El escorpionismo en Venezuela es un problema actual de salud pública producido por las especies de Tityus discrepans (TD) y Tityus zulianus (TZ). Los pacientes que presentan escorpionismo producido por TD desarrollan trastornos gastrointestinales y pancreáticos mientras que los afectados por TZ presentan una alta mortalidad y muestran una sintomatología relacionada a desordenes cardiopulmonares, los cuales parecen estar asociados a niveles elevados de las catecolaminas plasmáticas. Esta clínica diferente parece estar asociada a una composición distinta de toxinas de dichos venenos, lo cual ha sido previamente demostrado. En un intento de mimetizar o reproducir el escorpionismo en humanos se han realizado estudios toxinológicos con los venenos de TZ y TD utilizando varios biomodelos como son ratones y carneros anestesiados. El propósito de este trabajo fue evaluar, “in vivo” usando un Biomodelo (ratones), el papel de la estimulación del sistema nervioso autónomo (simpático) para producir algunos signos clínicos, vía la liberación de catecolaminas, en la fisiopatología del escorpionismo producido por TZ y TD. Así, los signos clínicos aquí descritos y observados durante 1 hr., después de la inyección de una dosis sub-letal de los venenos de TZ y TD, fueron la presencia de diarrea, diaforesis, salivación intensa, deshidratación, disnea y parálisis en las extremidades posteriores. Sin embargo, estos animales no presentaron vómitos, el cual es uno de los signos más frecuentemente observado en los pacientes con accidentes escorpiónicos por TD. Todos los animales inyectados con los venenos de TD y TZ presentaron diarrea especialmente en grupo TD. La disnea y la parálisis en los miembros posteriores fueron sólo observadas en el grupo de ratones inyectados con TZ. Las manifestaciones clínicas como son diarrea, diaforesis y la salivación intensa están asociadas a una activación del sistema nervioso autónomo...

Efeitos da Toxina TsTX-I isolada do veneno do Escorpião Tityus serrulatus sobre o hipocampo de ratos / Effects of TsTX-I toxin isolated from Tityus serrulatus scorpion venom on the hippocampus of rats

Os venenos escorpiônicos são compostos, entre outras substâncias , por neurotoxinas, polipeptídios básicos de baixo peso molecular que atuam sobre canais iônicos alterando a liberação de mediadoes químicos. O veneno do escorpião Tityus serrulatus tem sido extensamente estudado e muitas de suas toxinas já foram bem caracterizadas e sequenciadas. Entre as mais importantes se encontra a TsTX-I, uma toxina que se liga ao sítio 4 do canal de sódio, que já foi bem estudada quanto a seus periféricos, embora seus efeitos centrais sejam pouco conhecidos...

Scorpion venoms are composed mainly neurotoxins that are basic peptides with low molecular weight acting on ionic channels, mainly sodium channel, changing the release of chemical mediators. Crude venom of Tityus serrulatus scorpion as well its toxins, has already been extensively studied. Many of the venom toxins were well characterized and sequenced. TsTX- I is one of the most important toxin present in the the venom. This toxin actin by binding on site 4 of sodium channel, its peripherical effects have been well studied but its central effects are not well kmow...

Hemograma de cães submetidos ao envenenamento experimental por Tityus serrulatus / Canine blood profile after experimental envenomation by Tityus serrulatus

Avaliou-se o hemograma de 12 cães adultos, saudáveis (14,2±5,4kg) após a inoculação de veneno do escorpião amarelo (Tityus serrulatus). Os animais foram distribuídos em dois grupos (G), com seis em cada: os do GI foram usados como controle e receberam 0,5mL de salina tamponada com fosfato (PBS) por via subcutânea (SC) na face medial da coxa esquerda (FMCE), e os do GII receberam veneno liofilizado do T. serrulatus (250µg/kg) diluído em PBS por via SC na FMCE. Foram realizadas colheitas de sangue com anticoagulante EDTA a 10 por cento antes da inoculação do veneno (T0) e após 2h, (T1), 6h (T2), 12h (T3), 24h (T4), 48h (T5) e 72h (T6), para contagem de eritrócitos, leucócitos e plaquetas em aparelho contador eletrônico e esfregaços sanguíneos para contagem diferencial de leucócitos. Houve aumento significativo (P<0,05) dos valores de eritrócitos, volume globular e hemoglobina 2h e 6h após o envenenamento, devido à contração esplênica decorrente da dor local causada pelo veneno e pela liberação de catecolaminas. Foi observada leucocitose por aumento significativo (P<0,05) de neutrófilos e linfócitos 2h e 6h após o envenenamento. Concluiu-se que o veneno de Tityus serrulatus na dose de 250µg/kg, é capaz de aumentar os valores do eritrograma e do leucograma dos cães, provavelmente devido à dor local, com liberação de catecolaminas.

The canine blood profile after scorpion envenomation was evaluated using 12 healthy mongrel male dogs (14.2±5.4kg) distributed in two groups, with six animals in each: group I (control group) and group II (venom group). The lyophilized yellow scorpion (Tityus serrulatus) venom (250µg/kg) diluted in 0.5mL phosphate buffered saline (PBS) was given to group II animals by subcutaneous injection, in the medial face of the left thigh. Group I animals received only 0.5mL of PBS, by subcutaneous injection, in the medial face of the left thigh. Blood samples were collected with EDTA before (T0) and 2 (T1), 6 (T2), 12 (T3), 24 (T4), 48 (T5), and 72h (T6) after envenomation. Significant increases (P<0.05) in erythrocytes counting, hematocrit and hemoglobin concentration, 2 and 6h after envenomation were observed. Leukocytosis with significant increases (P<0.05) of neutrophils and lymphocytes 2 and 6h after envenomation was found. Then, T. serrulatus venom may induce alterations in blood profile in dogs, probably due to spleen contraction evoked by pain and catecholamines releasing.

Alterações bioquímicas e anátomo-histopatológicas causadas pelo veneno do escorpião Tityus fasciolatus em camundongos / Biochemical and anatomo-histopathogical alterations caused by Tityus fasciolatus scorpion venom in mice

O objetivo desta pesquisa foi estudar as alterações causadas pelo veneno de Tityus fasciolatus, uma espécie de escorpião encontrada no Brasil Central, sobre os tecidos, utilizando-se camundongos Swiss CF1, machos, com peso entre 18 e 20g como modelo experimental. Numa primeira parte do experimento, foi determinada a DL50 do veneno de T. fasciolatus, administrado por via subcutânea e foram avaliadas as alterações anátomo-histopatológicas dos animais que vieram a óbito. Numa segunda parte, foram estudados os efeitos de 24µg de veneno de T. fasciolatus sobre a bioquímica sanguínea, 1h, 8h e 24h após a inoculação por via subcutânea do veneno. A DL50 do veneno de T. fasciolatus para o camundongo foi de 59,65µg. Os achados macroscópicos encontrados foram áreas de hemorragia pulmonar (petéquias e equimoses) difusamente distribuídas pela superfície dos pulmões. Os corações apresentavam uma área de coloração mais clara, em formato de cunha no ápice, sugerindo área de infarto. Na microscopia observou-se hemorragia intersticial e presença de leucócitos nas paredes dos alvéolos; leve a moderada congestão dos vasos sanguíneos do epicárdio, miocárdio e endocárido e discreto infiltrado inflamatório linfo-histiocitário no endocárdio e miocárdio. Os animais da segunda parte, inoculados com 24µg de veneno de T. fasciolatus, não apresentaram alterações significativas nos valores de creatina quinase (CK), isoenzima CK-MB, aspartato aminotransferase (AST), lactato desidrogenase (LDH), amilase e glicose. Concluiu-se que o veneno de T. fasciolatus possui uma menor toxicidade quando comparada com o veneno de T. serrulatus e na dose de 24µg não alterou o perfil bioquímico sanguíneo em camundongos.

The aim of this study was to investigate the action of the venom the species Tityus fasciolatus scorpion, found in the Central of Brazil on the tissue using CF1 Swiss mice, male, (18-20kg) as experimental model. In the first part of the experiment, the LD50 of T. fasciolatus was determined by sub-cutaneous and evaluated the anatomo-pathological changes of the animals who died . In a second part, we studied the effects of 24ìg of venom of T. fasciolatus in the blood biochemistry, 1h, 8h and 24h after inoculation of the venom. The LD50 of the venom of T. fasciolatus for mice was 59.65 µg. The macroscopic findings were found with areas of pulmonary haemorrhage (petechiae and ecchymosis), diffusely distributed on the surface of the lungs. The hearts had a clearer field of colour in the wedge at the apex, suggesting infarcted area. Microscopy was observed in interstitial haemorrhage and presence of leukocytes in the alveolar walls, light to moderate congestion of the blood vessels of the epicardium, myocardium and endocardium and discrete hystiocitary lymphohistiocytic inflammatory infiltrate in the myocardium and endocardium. The second part of the animals inoculated with 24ìg of venom of T. fasciolatus showed no significant changes in the levels of creatine kinase (CK), CK-MB isoenzyme, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), amylase and glucose. It was concluded that the venom of T. fasciolatus has a lower toxicity when compared with the venom of T. serrulatus and the dose of 24ìg did not alter the blood biochemical profile in mice.

Asymmetric pulmonary edema after scorpion sting: a case report / Edema pulmonar assimétrico após picada de escorpião: relato de caso

A 12-year-old boy was referred with acute asymmetric pulmonary edema (APE) four-hour after scorpion sting to Emergency department. On admission, the main clinical manifestations were: dyspnea, tachypnea, and tachycardia. Chest x-ray revealed APE predominantly on the right hemithorax. The patient was treated with oxygen, intravenous frusemide and digoxin and discharged on the sixth hospital day in a good condition. This case report emphasizes the occurrence of asymmetric pulmonary edema after severe scorpion envenomation within few hours immediately after the sting.

Menino de 12 anos foi internado no Pronto Socorro, com edema pulmonar assimétrico agudo (APE), quatro horas após picada de escorpião. À admissão, as principais manifestações clínicas foram: dispnéa, taquipnéa e taquicardia. Raio X do pulmão revelou APE predominantemente no hemitórax direito. O paciente foi tratado com oxigênio, frusemida intravenosa e digoxina e teve alta no sexto dia de internação, em boas condições. Este relato de caso enfatiza a ocorrência de edema pulmonar assimétrico algumas horas após a picada.

Envenenamiento por pez escorpión (Scorpaena plumieri) en comunidad pesquera y turística de la península de Paraguaná, estado Falcón Venezuela: aspecto clínicos, epidemiológicos y tratamiento / Scorpionfish (Scorpaena plumieri) envenomation in a fishing and turistic community pf Paraguaná peninsula Falcon state Venezuela: clinical, epidemiological and treatment aspects

Entre diciembre 2006 y abril de 2007, se realizó un estudio descriptivo y prospectivo para analizar los perfiles clínicos, epidemiológicos y del tratamiento de los envenenamientos ocasionados por el pez escorpión Scorpaena plumieri en 36 individuos que se presentaron en la emergencia ambulatoria de Adícora, estado Falcón, Venezuela. Los porcentajes de envenenamientos no fueron estadísticamente significativos entre sexos ni grupos etarios (X2=0,03, p= 0,758; X2=0,06; p= 0,81, respectivamente). Los accidentes predominaron durante los meses festivos de febrero y abril (> 50%), lo que sugiere un patrón estacional, en horas vespertinas (83,33%) y a orillas de la playa (97,22%). Los pacientes asistieron a la emergencia ambulatoria entre 3 a 30 min después del accidente, con un tiempo promedio de 5,97 ± 4,39. Las heridas se presentaron de forma cortante, localizadas en su totalidad en la región plantar del pie, con longitudes entre 0,2 a 3 cm ( =1,04 ± 0,86) y profundidad entre 1 y 2 mm. Las manifestaciones clínicas observadas fueron: dolor intenso e irradiado (100%) [escala visual analógica VAS= : 9,39 ± 0,60], edema (27,78%) y eritema (22,22%). Un individuo presentó complicaciones sistémicas: hipotensión y desmayo. El tratamiento consistió de lidocaína (1%) infiltrada, anti-inflamatorio-analgésico sistémico vía oral (100 mg, cada 8 horas por 5 días) y antibióticoterapia per os (500 mg/2 veces al día/ 10 días), con evolución postratamiento satisfactoria entre 5 a 120 min ( = 30,11 ± 33,30) VAS de dolor promedio significativamente menor (0,72 ± 0,62; t= 52,2, p= 0,0001).

Efecto del veneno del escorpión Tityus discrepans sobre las pruebas globales de la coagulación: estudios preliminares / Effect of Tityus discrepans scorpion venom on global coagulation test: preliminary studies

El veneno del escorpión Tityus discrepans (Td) altera los tiempos de coagulación en humanos. En este trabajo se estudió el efecto in vitro de este veneno sobre el tiempo de tromboplastina parcial (TTP), el tiempo de protrombina (TP) y su actividad coagulante directa, utilizando como substrato plasma humano fresco y/o fibrinógeno purificado. El veneno completo (VC) fue fraccionado con una columna de exclusión molecular Protein Pak 125™ (0,5 mL/min, CH3COONH4 20 mM, pH 4,7). Seis fracciones (F1 a F6) eluyeron con tiempos de retención entre 12,8 y 31 minutos. El VC (78-625 µg/mL) y la fracción F1 (10-42,5 µg/mL), acortaron el TTP; el VC (700-1000 µg/mL) y la fracción F6 (16,5-700 µg/mL), alargaron esta prueba. El VC (40-240 µg/mL) y la fracción F2 (5-40 µg/mL), prolongaron el TP. No se detectó actividad coagulante parecida a trombina sobre plasma humano o fibrinógeno purificado. Estos resultados evidencian que en el veneno de Td existen componentes con acción procoagulante, que acortan el TTP. Además, presenta componentes anticoagulantes que inducen un alargamiento del TP y TTP.

Outcome of scorpion sting envenomation after a protocol guided therapy.

OBJECTIVE: Scorpion sting (SS) envenomation is a life threatening emergency in children, though not so severe in adults. Attempt to develop protocol using prazosin and dobutamine and few other drugs to treat SS. METHODS: Children aged 0-13 years with a history of scorpion sting were studied. Clinical features, complications, drug therapy and outcome of the cases for the period 1992-97(N = 186) was collected by the authors and also from the medical records department (RETROSPECTIVE GROUP). Cases treated during 1997-2000 (N = 198) as per the protocol were recorded as PROSPECTIVE GROUP. All the cases were observed for at least for 24 hours. Cases coming within 4 hours of a sting were given a dose of Prazosin (30 mic.gm/Kg/dose) and were observed. Those who came after 4 hours & were asymptomatic received only symptomatic treatment. Cases with signs of envenomation received Prazosin every 6 hourly till recovery. Cases having acute pulmonary edema (APE) were treated with dobutamine and sodium nitroprusside drip. Complicated cases were monitored in PICU as per the protocol. RESULT: Complications associated with excessive parasympathetic and sympathetic stimulation were observed. Myocarditis was observed due to the toxin and excessive catecholamine, which complicated in left ventricular failure (LVF) and APE. Nearly half of the children with acute myocarditis developed APE. Death was mainly due to myocarditis and APE, with or without encephalopathy. Mortality was high in children who received steroid and antihistaminics outside and who came late (> 4 hours). CONCLUSION: Complication rate remained almost same in both the groups. There was a significant reduction in overall mortality (P = < 0.0155) and in deaths associated with APE (P = < 0.0001) after the protocol guided therapy. There was also a reduction in mortality in encephalopathy group though not statistically significant. This treatment protocol and aggressive management of APE reduced the mortality due to SS significantly.

Increase of gastric area and weight gain in rats submitted to the ingestion of gasified water

PURPOSE: Due to the progressive increasing in the use of gasified drinks and weight gain in the Brazilian population, in addition to the fact that carbonic gas is present in all soft drinks, an experimental study was conducted using rats as the subject to investigate the effects of gasified water in the hydric ingestion and food intake, weight gain, gastric area, blood sugar, hematocrit, and hemoglobin. METHODS: Four groups of 12 rats were studied for 36 days while receiving the following daily diet, four times per day: Group 1- 35g/day of rat food "ad libitum" and 20ml of non-gasified water; Group 2 - 35g/day of rat food "ad libitum" and 20 ml of gasified water; Group 3 -10g/day of rat food "ad libitum" and 20ml of non-gasified water; and Group 4 - l0g/day of rat food "ad libitum" and 20ml of gasified water. RESULTS: The results showed that the animals submitted to the treatment with gasified water (Groups 2 and 4), presented a larger volume of hydric ingestion and significant increase of the gastric area (p<0,001). In group 2, the food intake and the weight gain were significant (p<0,01). Blood sugar, hematocrit and hemoglobin data didn't show significant alterations among the studied groups. CONCLUSION: The authors of this study concluded that gasified water favored the hydric ingestion, food intake, and weight gain, as well as expanded the gastric area.

Prolonged atrio - ventricular block following scorpion bite: a case report

This report describes a 55-year-old woman in whom yellow scorpion sting resulted in the development of Mobitz type 1 and transient complete heart blocks unresponsive to atropine administration. It might be concluded that although autonomic involvement including parasympathetic overactivity is present in such cases, other factors such as toxic damage to the cardiac conduction system may play a role in the development of some of the cardiovascular manifestations of scorpion toxin

Effects of scorpion Tityus serrulatus venom toxin TS-8F on rat learning and memory

Scorpion venom neurotoxins are responsible for toxicity and pharmacological effects. They are active in sodium and potassium channels leading to an increase in the release of neurotransmitters, such as glutamate. Glutamate is found in large quantities in the hippocampus (HPC) and is involved in the long-term potentiation (LTP) induction. The HPC is known to be related to certain kinds of memory. The aim of this study is to evaluate the effects of Tityus serrulatus TS-8F toxin on rat behavior with emphasis on learning and memory. We analyzed the effects of different doses of TS-8F on rat behavior in home cages, open-field (habituation), inhibitory avoidance, T-maze, and hippocampus morphology. In the first two experiments, 0.05µg/animal dose of TS-8F did not cause convulsion but led to a decrease in locomotion (LO) frequency in the open-field first session. During the second session, rats receiving 0.03µg/animal TS-8F showed a decrease in LO and rearing frequency (RE); controls only showed decreased LO; and those receiving 0.05µg/animal showed no significant changes. In inhibitory avoidance, T-maze, and HPC morphology experiments no significant differences were observed. It is concluded that TS-8F may exert some influence in rat learning and memory and seems to be useful as a pharmacological tool. Further research is required to elucidate all possible uses of this toxin.

Induction of acute and chronic pancreatitis with the use of the toxin of the scorpion Tityus serrulatus: experimental model in rats

We observed that the purified venom of the Tityus serrulatus scorpion (T1 fraction), injected IV in rats, in a single dose of 0,5 mg/kg, produces: acute pancreatitis, characterized by degranulation and acinar cell vacuolization, necrosis and an inflammatory reaction, 24, 48 and 96 hours after the injection; chronic pancreatitis, characterized by interstitial fibrosis, lymphocyte infiltration, ductal and ductular dilation, acinar cell atrophy, periductal ductular hyperplasia, 20 days after injection; hyperplasia of Langerhans' islets and nesidioblastosis, associated to chronic pancreatitis. The absence of deaths in the experimental group is an intersting finding: the dose used preserved the animals from death and allowed the safe follow-up ot the progression of the provoked pancreatitis. The results led us to conclude that the toxin of Tityus serrulatus scorpion is an agent of considerable efficacy in the induction of pancreatitis in rats providing an experimental model of acute and chronic form of this disease.

Protección contra el alacranismo / Protectión agains scorpionism

En este capítulo se revisan algunos aspectos del problema del alacranismo en México. Se discuten algunos datos obtenidos con una vacuna experimental animal, para la cual el antígeno fue generado por polimerización de extractos solubles de glándulas venenosas de alacranes mexicanos. Se da énfasis a la discusión de los procedimientos y datos bioquímicos más importantes obtenidos en el fraccionamiento del veneno soluble extraído por estimulación eléctrica de telsons de alacranes vivos. También se mencionan algunas propiedades inmunológicas de los extractos de las glándulas, del veneno soluble, de sus fracciones cromatográficas y de sus polipéptidos altamente purificados. Finalmente, se presentan datos sobre la inmunización de ratones con péptidos sintéticos, diseñados con base en la secuencia de aminoácidos de las toxinas de alacranes. Las perspectivas futuras de este trabajo se enfocan a la determinación de los epítopos protectores de las toxinas del veneno y a la clonación y modificación por ingeniería genética de genes que codifican para estos péptidos tóxicos. No obstante el vasto trabajo experimental realizado, todavía no existe una vacuna disponible contra los efectos neurotóxicos del veneno de alacrán. Desde el punto de vista médico, el problema del envenenamiento por piquete de alacrán debe ser tratado mediante el uso del suero antialacrán, única medicina de elección para el tratamiento de los casos severos de accidentes con estos arácnidos