ABSTRACT
Almost all marine snails within superfamily Conoidea produce venoms containing numerous neuroactive peptides. Most toxins characterized from members of this superfamily are produced by species belonging to family Conidae. These toxins (conotoxins) affect diverse membrane proteins, such as voltage- and ligand-gated ion channels, including nicotinic acetylcholine receptors (nAChRs). Family Turridae has been considerably less studied than their Conidae counterpart and, therefore, turrid toxins (turritoxins) have just been barely described. Consequently, in this work the most prominent chromatographic (RP-HPLC) fractions from the East Pacific species Polystira nobilis venom duct extract were isolated. The biological activity of six selected fractions was assayed on human (h) α7 AChRs expressed in Xenopus laevis oocytes. One of these fractions, F21, inhibited the acetylcholine-elicited response by 62 ± 12%. Therefore, this fraction was further purified and the F21-2 peptide was obtained. This peptide (at 5.6 µM) strongly and irreversibly inhibited the acetylcholine-induced response on hα7 and hα3ß2 nAChRs, by 55 ± 4 and 91 ± 1%, respectively. Electrospray mass spectrometry indicates that the average molecular mass of this toxin is 12 358.80 Da. The affinity for hα3ß2 nAChRs is high (IC50 of 566.2 nM). A partial sequence without cysteines was obtained by automated Edman degradation: WFRSFKSYYGHHGSVYRPNEPNFRSFAS ; blastp search revealed that this sequence has low similarity to some non-Cys-containing turripeptides. This is the first report of a turritoxin from a species of the American Pacific and the second description of a turripeptide inhibiting nAChRs.
Subject(s)
Conotoxins/pharmacology , Mollusk Venoms , Receptors, Nicotinic/drug effects , Animals , Humans , Mollusk Venoms/chemistry , Mollusk Venoms/isolation & purification , Mollusk Venoms/metabolism , Mollusk Venoms/toxicity , Oocytes , Recombinant Proteins/pharmacology , Snails/metabolism , Xenopus laevisABSTRACT
Background: It is estimated that venoms of marine cone snails (genus Conus) contain more than 100,000 different small peptides with a wide range of pharmacological and biological actions. Some of these peptides were developed into potential therapeutic agents and as molecular tools to understand biological functions of nervous and cardiovascular systems. In this study we examined the cytotoxic and anticancer properties of the marine vermivorous cone snail Conus vexillum (collected from Hurgada and Sharm El-Shaikh, Red Sea, Egypt) and suggest the possible mechanisms involved. The in vitro cytotoxic effects of Conus venom were assessed against Ehrlich's ascites carcinoma (EAC) cells. Results: Conus venom treatment resulted in concentration-dependent cytotoxicity as indicated by a lactate dehydrogenase leakage assay. Apoptotic effects were measured in vivo by measuring levels of reactive oxygen species and oxidative defense agents in albino mice injected with EAC cells. Conus venom (1.25 mg/kg) induced a significant increase (p < 0.05) in several oxidative stress biomarkers (lipid peroxidation, protein carbonyl content and reactive nitrogen intermediates) of EAC cells after 3, 6, 9 and 12 hours of venom injection. Conus venom significantly reduced (p < 0.05) the activities of oxidative defense enzymes (catalase and superoxide dismutase) as well as the total antioxidant capacity of EAC cells, as evidenced by lowered levels of reduced glutathione. Conclusions: These results demonstrate the cytotoxic potential of C. vexillum venom by inducing oxidative stress mediated mechanisms in tumor cells and suggest that the venom contains novel molecules with potential anticancer activity.(AU)
Subject(s)
Animals , Male , Mice , Carcinoma, Ehrlich Tumor , Oxidative Stress , Conus Snail/cytology , Mollusk Venoms/toxicity , Mollusk Venoms/pharmacology , In Vitro Techniques , Apoptosis/physiology , Egypt , Antineoplastic Agents/pharmacologyABSTRACT
Mollusks of the genus Conus present a venomous apparatus composed of radulae, a chitin structure linked to glands, which injects potent neurotoxic peptides, causing serious human envenomation and even death, associated with the blockage of certain receptors and muscular paralysis. No reported envenomation has occurred in Brazil, but certain populations are at risk of accidents.
Os moluscos do gênero Conus apresentam um aparato venenoso composto de uma rádula quitinosa ligada a glândulas de peçonha, causando envenenamentos humanos graves e mesmo óbitos pela ação neurotóxica indutora do bloqueio de vários receptores e paralisia muscular. Não há casos descritos de envenenamento no país, mas determinadas populações correm risco de acidentes.
Subject(s)
Humans , Animals , Conus Snail , Conotoxins/toxicity , Mollusk Venoms/toxicity , Neurotoxins/toxicity , Brazil , Risk FactorsABSTRACT
Los florecimientos algales nocivos (FANs), corresponden al fenómeno comúnmente denominado marea roja. Esta se encuentra constituida por 5 tipos de venenos diferentes: veneno paralizante de moluscos (VPM); veneno diarreico de moluscos (VDM); veneno amnésico de moluscos (VAM); veneno neuro-tóxico de moluscos (VNM) y toxinas producidas por cianobacterias, cada una de las cuales presenta una distribución a nivel mundial. En Chile, sólo han sido identificados los venenos VPM y VDM, los que se encuentran endémicamente desde la X a XII regiones. Su identificación a nivel nacional, se realiza a través del método denominado bioensayo en ratón, el cual presenta una sensibilidad adecuada para la detección de VPM, no así para la detección de VDM, debido a las cualidades químicas que presentan estas toxinas, produciéndose cada año un número no estimado de personas intoxicadas. Dadas las características socioeconómicas del sur de Chile, la mayoría de los bivalvos son expendidos bajo condiciones de ahumado, de manera de aumentar su preservación para el consumo por parte de la población local. Esto ocasiona la fijación de hidrocarburos aromáticos policíclicos (HAPs) en los bivalvos de manera extrema. Considerando que los HAPs son iniciadores y el VDM promotor del proceso carcinogénico, sumándose a ello la importancia de este tipo de alimento en la dieta diaria de la población, en este trabajo se identificaron y cuantificaron las concentraciones HAP y VDM presentes en bivalvos de la X Región. Los resultados, muestran que los HAPs y VDM presentes en los bivalvos sobrepasan la norma internacional 10 µg/kg y 200 ng/g de hepatopáncreas, respectivamente. Siendo el HAP más relevante el benzopireno (71,62 ± 18,40 µg/kg en cholgas) y la toxina VDM identificada DTX-3 (217,33 ± 14,76 ng/g de hepatopáncreas en cholgas). Estos resultados ponen en evidencia la necesidad de realizar estudios epidemiológicos en la zona para determinar si existe una asociación entre la exposición a estos compuestos y la incidencia de cáncer gástrico de la población local.
Subject(s)
Humans , Benzopyrenes/toxicity , Carcinogens , Dinoflagellida/pathogenicity , Polycyclic Aromatic Hydrocarbons/toxicity , Foodborne Diseases , Stomach Neoplasms , Mollusk Venoms/analysis , Mollusk Venoms/toxicity , Biological Assay , ChileABSTRACT
De los caracoles, la familia Conidae o en forma de cono son los únicos que se sabe que pueden producir picaduras venenosas mortales. Se localizan en todos los mares tropicales del mundo en sustratos arenosos y rocosos. Es importante tener precaución al manipular cualquier caracol en forma de cono. No existe un antídoto conocido, el tratamiento médico es sintomático. Se muestra el manejo médico conocido que ha tenido éxito en evitar un desenlace fatal
Subject(s)
Mollusk Venoms/poisoning , Mollusk Venoms/toxicityABSTRACT
This paper describes an outbreak of paralytic shellfish poisoning (PSP), affecting human populations on the Pacific Coast of Costa Rica in October 1989. Numbness in arms, face and legs occurred 30 to 45 minutes after ingestion of the large clam Spondylus calcifer. Paralysis of legs and respiratory symptoms followed, often persisting for one week. Large amounts of the dinoflagellate Pyrodinium bahamense were found in the intestine of the mollusk. A toxin was detected in crude or filtered and heated macerates of intestine, muscle, mantle and hepatopancreas of S. calcifer, and to a lesser extent Tagelus sp., by injection of its crude or diluted extracts in white mice. The effects in mice consisted in paralysis and asphyxia generally leading to death in less than 5 minutes, compatible with saxitoxin. Mice were killed by the toxin in macerates diluted 1:100 to 1:1000. No toxin was detected in Anadara tuberculosa (Bivalvia) or in peneids. Prevention rests on intersectoral actions between state and private sectors in charge of fishing, distribution and marketing of shellfish, as well as on education of the population at large.
Subject(s)
Bivalvia/parasitology , Dinoflagellida/isolation & purification , Disease Outbreaks , Mollusk Venoms/toxicity , Paralysis/epidemiology , Shellfish Poisoning , Adult , Aged , Animals , Child , Costa Rica/epidemiology , Humans , Intestines/parasitology , Mice , Paralysis/etiologyABSTRACT
Se estudió un brote de intoxicación paralítica por mariscos (IPM) que afectó varias poblaciones humanas de la Costa Pacífica de Costa Rica, en octubre de 1989. El cuadro clínico en adultos consistió en adormecimiento de brazos, cara y piernas, 30 a 45 minutos después de ingerir moluscos crudos. El cuadro se acompaño de dificuldad o incapacidad para caminar (parálisis) y síntomas respiratorios y neurológicos durante varios días. El principal transvector fue el "ostión vaca" (Spondylus calcifer) el cual contenía en su intestino grandes cantidades de Pyrodinium bahamense. Por inoculación de ratones blancos se demostró una toxina en preparaciones crudas y filtradas de intestino, músculo, manto y hepatopáncreas del ostión vaca y, en menor grado, de "navajas" (Tagelus sp.). El efecto de la toxina fue inmediato, y consitió em parálisis seguida de muerte por asfixia. La toxina es resistente al calor y no ocasiona alteraciones en la apariencia y características organolépticas de los tejidos del molusco. No se demostró toxina en "pianguas" (Anadara tuberculosa) ni en camarones peneidos. Se recomienda establecer un sistema de vigilancia de la marea roja, el examen periódico de mariscos en esa época, la educación del personal a cargo de la pesca y comercialización de moluscos, y la educación de la comunidad y personal de salud para reconocer los casos leves y moderados