Understanding the complexity of Tityus serrulatus venom: A focus on high molecular weight components

Tityus serrulatus scorpion is responsible for a significant number of envenomings in Brazil, ranging from mild to severe, and in some cases, leading to fatalities. While supportive care is the primary treatment modality, moderate and severe cases require antivenom administration despite potential limitations and adverse effects. The remarkable proliferation of T. serrulatus scorpions, attributed to their biology and asexual reproduction, contributes to a high incidence of envenomation. T. serrulatus scorpion venom predominantly consists of short proteins acting as neurotoxins (α and ß), that primarily target ion channels. Nevertheless, high molecular weight compounds, including metalloproteases, serine proteases, phospholipases, and hyaluronidases, are also present in the venom. These compounds play a crucial role in envenomation, influencing the severity of symptoms and the spread of venom. This review endeavors to comprehensively understand the T. serrulatus scorpion venom by elucidating the primary high molecular weight compounds and exploring their potential contributions to envenomation. Understanding these compounds' mechanisms of action can aid in developing more effective treatments and prevention strategies, ultimately mitigating the impact of scorpion envenomation on public health in Brazil.

Mass fingerprinting and electrophysiological analysis of the venom from the scorpion Centruroides hirsutipalpus (Scorpiones: Buthidae)

Background Centruroides hirsutipalpus, of the family Buthidae, is a scorpion endemic to the Western Pacific region of Mexico. Although medically important, its venom has not yet been studied. Therefore, this communication aims to identify their venom components and possible functions. Methods Fingerprinting mass analysis of the soluble venom from this scorpion was achieved by high-performance liquid chromatography and electrospray mass spectrometry. Furthermore, the soluble venom and its toxic effects were evaluated extensively via electrophysiological assays in HEK cells expressing human voltage-gated Na+ channels (hNav 1.1 to Nav1.6), CHO cells expressing hNav 1.7, potassium channel hERG 1 (Ether-à-go-go-related-gene) and the human K+-channel hKv1.1. Results The separation of soluble venom produced 60 fractions from which 83 distinct components were identified. The molecular mass distribution of these components varies from 340 to 21,120 Da. Most of the peptides have a molecular weight between 7001 and 8000 Da (46% components), a range that usually corresponds to peptides known to affect Na+ channels. Peptides with molecular masses from 3000 to 5000 Da (28% of the components) were identified within the range corresponding to K+-channel blocking toxins. Two peptides were obtained in pure format and completely sequenced: one with 29 amino acids, showing sequence similarity to an "orphan peptide" of C. limpidus, and the other with 65 amino acid residues shown to be an arthropod toxin (lethal to crustaceans and toxic to crickets). The electrophysiological results of the whole soluble venom show a beta type modification of the currents of channels Nav1.1, Nav1.2 and Nav1.6. The main effect observed in channels hERG and hKv 1.1 was a reduction of the currents. ..

Mild reproductive effects of the Tityus bahiensis scorpion venom in rats

Scorpion envenoming is a public health problem in Brazil, where Tityus serrulatus and T. bahiensis are considered the most dangerous scorpions. They are well adapted to urbanized environments, and there is an increasing probability of human exposure to these venoms, including during pregnancy. Not much is known about the effects of prenatal exposure to the venom, and no information is available to aid in the rational treatment of victims stung during pregnancy. Thus, this study aimed to investigate whether venom from the scorpion T. bahiensis administered once to pregnant female rats at a dose that causes a moderate envenomation may lead to deleterious effects on the reproductive performance of the dams and on the development of their offspring. This is the first work demonstrating that T. bahiensis venom, when administered experimentally to rats, alters maternal reproductive performance and the morphological development of fetuses. The venom was given to dams on the 5th (GD5) or on the 10th (GD10) gestational day. After laparotomy, on GD21, fetuses and placentas were counted, weighed and externally analyzed. The corpora lutea were counted. The sex and vitality of fetuses were evaluated, and each litter was then randomly divided for visceral or skeletal analyses. Data were analyzed by ANOVA followed by the Tukey-Kramer test and Fisher's exact test. The significance level for all tests was set at p < 0.05.

Mild reproductive effects of the Tityus bahiensis scorpion venom in rats

Scorpion envenoming is a public health problem in Brazil, where Tityus serrulatus and T. bahiensis are considered the most dangerous scorpions. They are well adapted to urbanized environments, and there is an increasing probability of human exposure to these venoms, including during pregnancy. Not much is known about the effects of prenatal exposure to the venom, and no information is available to aid in the rational treatment of victims stung during pregnancy. Thus, this study aimed to investigate whether venom from the scorpion T. bahiensis administered once to pregnant female rats at a dose that causes a moderate envenomation may lead to deleterious effects on the reproductive performance of the dams and on the development of their offspring. This is the first work demonstrating that T. bahiensis venom, when administered experimentally to rats, alters maternal reproductive performance and the morphological development of fetuses. The venom was given to dams on the 5th (GD5) or on the 10th (GD10) gestational day. After laparotomy, on GD21, fetuses and placentas were counted, weighed and externally analyzed. The corpora lutea were counted. The sex and vitality of fetuses were evaluated, and each litter was then randomly divided for visceral or skeletal analyses. Data were analyzed by ANOVA followed by the Tukey-Kramer test and Fisher's exact test. The significance level for all tests was set at p < 0.05.

Anticoagulant and factor Xa-like activities of Tityus discrepans scorpion venom

Tityus discrepans venom (TdV) produces a variety of haemostatic manifestations including alveoli fbrin deposition and/ or prothrombin and partial thromboplastin time (PT, PTT) alterations in mammals. In vitro studies have demonstrated that TdV contains tissue plasminogen activator-like (t-PA), fbrinolytic and plasmin inhibitory compounds and produces platelets activation through GPVI and a novel Src-dependent signalling pathway. The aim of this study is to describe the initial characterization of procoagulant and anticoagulant components from TdV. This venom was fractionated by exclusion molecular chromatography on a Sephadex G-50 column. The eluted material was collected as fve fractions called S1 to S5. These fractions and the whole venom were used to evaluate factor Xa- and thrombin-like activities, fbrinogen degradation, furthermore thrombin- and factor Xa-inhibitory activities. The results demonstrated that TdV contain components with factor Xa-like activity (procoagulants) as well fbrinogenolytic compounds present in the fraction S1 and components with factor Xa inhibitory activity in the fractions S4 and S5 (anticoagulants).

El veneno de Tityus discrepans (TdV) produce en mamíferos una variedad de manifestaciones hemostáticas tales como depósitos de fbrina en alveolos y/o alteración en los tiempos de protrombina y tromboplastina parcial (PT, PTT). Estudios in vitro han demostrado que el TdV contiene componentes semejantes al activador del plasminógeno tipo tisular (t-PA), fbrino-líticos, compuestos que inhiben la actividad de plasmina y además componentes que promueven la activación de plaquetas a través del receptor GPVI y por una nueva vía de señalización dependiente de las Src kinasas. El objetivo de este estudio es describir la caracterización inicial de componentes procoagulantes y anticoagulantes a partir del TdV. Este veneno fue fraccionado por cromatografía de exclusión molecular sobre una columna Sephadex G-50. El material eluido fue colectado en cinco fracciones denominadas S1 a S5. Estas fracciones y el veneno completo fueron usados para evaluar actividades semejantes a factor Xa y trombina, degradación de fbrinógeno, como también la inhibición de la actividad del factor Xa y de la trombina. Los resultados demostraron que TdV contiene componentes con actividad semejante al factor Xa (procoagulantes) y compuestos fbrinogenolíticos presentes en la fracción S1, además de componentes con actividad inhibitoria del factor Xa presentes en la fracción S4 y S5 (anticoagulantes).

Effects of atropine and propranolol on lung inflammation in experimental envenomation: comparison of two buthidae venoms

Previous works had shown that scorpion venom induced neurotransmitter elevation and an inflammatory response associated with various anatomo-pathological modifications. The most dangerous scorpions species in Algeria responsible for these effects are Androctonus australis hector(Aah) and Androctonus amoreuxi (Aam). Results Comparison of the physiopathological effects induced by the two venoms showed differences in the kinetic of cytokine release and in lung injury. The lung edema was only observed in response to Aah venom and it was correlated with cell infiltration. In order to better understand the involved mechanism in inflammatory response, we used two antagonists, atropine (non-selective muscarinic antagonist) and propranolol (β adrenergic antagonist), which lead to a decrease of cell infiltration but has no effect on edema forming.Conclusion These results suggest another pathway in the development of lung injury following envenomation with Aam or Aah venom.

IIhotas pancreáticas humanas viáveis para o transplante através do aumento da massa de células e do imunoisolamento com microcápsulas biocompatíveis / Obtention of human pancreatic islets for transplantation through an increase in cell mass and an immunoisolation with biocompatible microcapsules

O transplante de ilhotas pancreáticas humanas representa uma estratégia promissora para a cura do diabetes mellitus tipo 1 (DM1) mas a aplicação a todos os pacientes diabéticos ainda é impraticável devido à limitada disponibilidade de ilhotas ou células β e à necessidade de utilização de drogas imunossupressoras pelo paciente transplantado. O tratamento com imunossupressores após o transplante de ilhotas pode ser abolido quando se realiza o microencapsulamento das ilhotas pancreáticas. Neste trabalho investigou-se um novo biomaterial, Biodritina (alginato/sulfato de condroitina) adequado ao microencapsulamento que gelifica na presença de íons de cálcio ou bário. A biocompatibilidade das microcápsulas tem sido avaliada segundo o grau de pureza do alginato utilizado na sua confecção. Amostras de alginato comercial purificado foram analisadas, comprovando-se a presença de impurezas (polifenóis, endotoxinas, proteínas) em níveis elevados, que impedem sua aplicação clínica. Optou-se, portanto pela utilização do alginato comercial ultrapurificado nos experimentos descritos neste trabalho. Das formulações de biomateriais avaliadas, as microcápsulas de bário-Biodritina apresentaram o melhor desempenho em testes de estabilidade físico-química...

Biochemical changes and manifestations of envenomation produced by Odonthobuthus doriae venom in rabbits

Many toxins from scorpion venoms cause neurotransmitters release by activating the autonomic system. The aim of the present work was to determine osmotic fragility of red blood cells (RBCs) and serum biochemical changes produced by the venom of Odonthobuthus doriae (O. doriae), a dangerous species of scorpion in Iran. For this study we selected 2 groups, each one containing 10 New Zealand white rabbits weighing 2 ± 0.2 kg. In vivo and in vitro osmotic fragilities as well as packed cell volume (PCV) were determined. Serum was separated and used for determination of glucose, blood urea nitrogen (BUN), creatinine, uric acid (UA), triglycerides, cholesterol, aspartate aminotransferase (AST, EC 2.6.1.1), and alanine aminotransferase (ALT, EC 2.6.1.2). Results indicate that Odonthobuthus doriae venom (0.5 mg/kg, IV) causes a significant increase (p<0.05) of serum glucose, UA, PCV, ALT, and AST. Increase was also observed in BUN, but it was not statistically significant. On the other hand a significant decrease (p<0.05) was observed in triglycerides and cholesterol levels. Increased in vivo osmotic fragility of RBCs was significant too, but in vitro osmotic fragility did not show a significant change. These results support the hypothesis that the biochemical variation caused by scorpion venom can be due to an autonomic storm and release of catecholamines.(AU)

Enponzoñamiento escorpiónico: concentración de veneno en plasma y su efecto desencadenante de la respuesta inflamatoria sistémica / Scorpion venom as a triggering factor of systemic inflammatory response

Se estudió el efecto del veneno con desencadenante de mediadores de respuesta sistémica. Para ello se utilizó un test de ELISA desarrollado en el Instituto de Investigaciones Científicas que permitió discernir en la emergencia cuales pacientes recibieron veneno y racionalizar el uso del antiveneno en el momento de la admisión del paciente. El objetivo de este trabajo es correlacionar los grados de intensidad clínica con las concentraciones del veneno, cifras de amilasa, glicemia, y la interleuquina 1 (IL-1 alfa), interleuquina 6 (IL-6), factor de necrosis tumoral a (TNF alfa), óxido nítrico (NO). Se determinaron estos valores en 96 pacientes pediátricos que acudieron a la emergencia del Hospital Victorino Santaella de Los Teques con emponzoñamiento escorpiónico por T. discrepans, entre mayo de 2001 y mayo de 2002 utilizando criterios de inclusión, clasificado el emponzoñamiento y la terapia específica de acuerdo a las pautas del Hospital Victorino Santaella de Los Teques. Obteniendo resultados expresados en medianas y sus intervalos de confianza al 95 por ciento, que reflejaron una correlación entre la concentración de veneno en plasma y la gravedad del escorpionismo. Las citoquinas estudiadas revelaron un estudio similar con predominio de la interleuquina 6 y el óxido nítrico. Nuestros resultados demuestran que el veneno del escorpión es capaz de producir un cuadro de respuesta inflamatoria sistémica, de allí la iportancia de colocar la antivenina precozmente sin esperar el efecto desencadenante de los mediadores de la cascada inflamatoria cuyo proceso es difícil detener y sus consecuencias pueden incidir en un mayor deterioro del paciente

Lethal effect of the scorpion Tityus serrulatus venom: comparative study on adult and weanling rats

Scorpion sting accidents are common in Brazil and several lethal cases occur among children. This observation can be due to higher concentration of circulating venon in children. However, other factors such as those related to the growth and development of the organism might modulate differently children and adult envenomation. The present work aimed to compare acute toxicity, by median lethal doses (LD50) evaluation, using weanling male and female (21-22 days) and adult (150-160 days) rats, after subcutaneous injection with saline extract of crude venom. The LD50 values, expressed as mg of venom protein per kg of rat body weight, were calculated according to the statistical Probit method...

Venezuelan arachnids. Two new species of the Tityus Genus (Scorpionida: Buthidae) and the chromatographic profile of venom as a possible taxonomical tool

Two new species of the Tityus genus are described. T. isabelceciliae n. sp lives on the northern central slope of the Cordillera de la Costa. It belongs to the discrepans group and is dangerous to man due to its high number, aggressive behavior, domiciliary habits, and high toxicity of its venom. T. isabelceciliae venom is similar to other Tityus in relation to the molecular weight range and the biological activity of its components. However, the proportions of each fraction in the venom pooled from many T. isabelceciliae differ from the proportions in other Tityus, indicating that these proportions may have a taxonomical value. The venom LD50 is 38.1 (36.3, 39.9) µg/g mouse (Death in 30 min, Dixon and Mood (14) sequential method, median and 95 per cent confidence interval, n=7). Venom production was 916 (625, 1213) µg protein per animal (n=38): females [944 (750, 1150) mg protein per animal, n=24] and males [824 (550, 112) mg protein per animal, n=14] did not differ in venom production (P>0.05). There was no correlation between animal total weight and venom production. T. rusmelyae n. sp. from the androcottoides group lives near the town of Humocaro Alto in the Lara State, Venezuela. The male specimens have clearly defined keels and granules. It differs from other species of this genus in that the prominent characteristics are observed in male specimens.

Accidente y cuadro clínico por la "picadura de alacranes en Costa Rica / Accident and clinic case for the bites of scorpion in Costa Rica

Las picaduras de alacranes en Costa Rica son frecuentes. En 1999 un total de 405 casos fueron reportados al Centro Nacional de Control de Intoxicaciones. Las manifestaciones clínicas más frecuentes en estos pacientes fueron dolor (44,7 por ciento), adormecimiento (26,7 por ciento) e inflamación de la zona afectada (13,8 por ciento). Las extremidades superiores en especial los dedos, fueron las partes del cuerpo donde se dio el mayor número de picaduras. Los adultos fueron los más afectados. Los síntomas son molestos pero en genreral el cuadro que presenta el paciente es benigno. En nuestro país, hasta la fecha no se han identificado especies que producen complicaciones sistémicas de importancia como las que se encuentran en otros lugares del mundo Es importante conocer si en la zona en que se habita suelen aparecer estos arácnidos para así tomar precauciones y disminuir el número de picaduras. (Rev Cost Cienc Med 2000; 21(3-4): 161-7). Palabras clave: picadura alacrán, hallazgos clínicos.

Escorpionismo en Venezuela / Scorpionism in Venezuela

El accidente derivado del empoñozamiento en humanos por escorpiones del género Tityus Koch en Venezuela produce un cuadro clínico cuya gravedad depende, entre otros factores, de la especie involucrada. Hasta el momento, sólo se han caracterizado toxicológicamente los venenos de Tityus deiscrepans (Karsch) y Tityus zulianus González-Sponga, especies que habitan las regiones Centro-Norte y Occidental del país, respectivamente, las cuales han ocacionado accidentes graves y muertes. Otras Tityus sp. que habitan el Sistema Coriano y el Macizo Oriental, junto con T.valerae Scorza del Estado Trujillo, también han sido responsables de casos agudos de empoñozamientos. Se presenta un análisis restrocpectivo del problema del escorpionismo en Venezuela, alertando sobre la necesidad de elaborar un mapa de letalidad para las especies peligrosas y el desarrollo de una suroterapia efectiva que permita neutralizar los venenos de importancia médica

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

Alacranismo / Scorpionism

El alacranismo es un problema de salud pública originado por la picadura de alacranes venenosos. Afecta a grandes núcleos de población tanto en el medio rural como urbano ocacionando considerables tasas de mortalidad. Históricamente se considera que las zonas de mayor riesgo de este accidente son la ciudad de Durango y el estado de Colima, pero la magnitud de este fenómeno abarca una gran extensión de México. Se pretende dar una visión general del agente agresor y su distribución en México. Se incluyen datos de casos registrados en la ciudad de León, Guanajuato y de los estados de Nayarit y Morelos. Se anotan algunos aspectos bioquímicos del veneno, su mecanismo de acción y fisiopatología. En algunos casos se mencionan especies de otros países, pero como discute más adelante, la homología existente entre toxinas de diferentes especies, sobre todo de Sudamérica, permite hacer analogías respecto al efecto ocasionado por especies mexicanas. Los datos experimentales con veneno de alacranes mexicanos son limitados a la fecha. Finalmente se abordan los factores de riesgo, sintomatología y tratamiento. Se discute su repercusión en la salud de la población y algunas alternativas para abordar este fenómeno

Histamine, 5-HT & hyaluronidase in the venom of the scorpion Lychas laevifrons (Pock).

Factors involved in the pathophysiological changes such as severe pain, burning sensation, redness, swelling and edema in case of the scorpion L. laevifrons were investigated. The presence of pain-producing autacoids histamine 2.1 +/- 0.18 micrograms/mg and 5-HT 0.23 +/- 0.1 micrograms/ml was confirmed by thin layer chromatography and bioassay. Histamine releasing substance was detected in vitro in the chopped guineapig lung. Venom also contained hyaluronidase 5 x 10(-4) N-acetyl-D-glucosamine released/h/mg, which facilitates spread of the toxic principles in the tissues. It is concluded that histamine, 5-HT, histamine-releasing factor and hyaluronidase are partly involved in the pathophysiological changes induced by the venom. It is suggested that mepyramine and cyproheptadine may prove useful in the management of scorpion envenomation.

In vitro neutralization of the scorpion, Buthus tamulus venom toxicity.

Scorpion (Buthus tamulus) venom was subjected to neutralization by treating the venom with various chemicals such as hydrochloric acid, sodium hydroxide, thiourea, formaldehyde, zinc sulphate, acetic acid and trichloroacetic acid. The venom was also subjected to heat treatment. The levels of total protein, free amino acids and protease activity in neutralized venom decreased significantly. The decrease in venom protein and free amino acids was in proportion to the duration of the heat treatment and the concentration of chemicals used except zinc sulphate, sodium hydroxide and thiourea. Protease activity of neutralized venom samples also showed a decrease except with zinc sulphate which enhanced the enzyme activity. Intramuscular injection of formaldehyde, trichlcroacetic acid and heat treated venoms into albino rats produced low mortality while thiourea and zinc sulphate were not effective in reducing the mortality. Hydrochloric acid and acetic acid treated venoms reduced the mortality by 50% with a decrease in the symptoms of envenomation. The changes were attributed to the denaturing of venom protein by chemical and heat treatments.