We identified Tf2, the first β-scorpion toxin from the venom of the Brazilian scorpion Tityus fasciolatus. Tf2 is identical to Tb2-II found in Tityus bahiensis. We found that Tf2 selectively activates human (h)Nav1.3, a neuronal voltage-gated sodium (Nav) subtype implicated in epilepsy and nociception. Tf2 shifts hNav1.3 activation voltage to more negative values, thereby opening the channel at resting membrane potentials. Seven other tested mammalian Nav channels (Nav1.1-1.2; Nav1.4-1.8) expressed in Xenopus oocytes are insensitive upon application of 1 μM Tf2. Therefore, the identification of Tf2 represents a unique addition to the repertoire of animal toxins that can be used to investigate Nav channel function.
Injuries caused by aquatic animals in Brazil in most cases are provoked by marine and freshwater catfish. Pimelodus maculatus is a freshwater catfish very common in Brazilian basins that causes frequent accidents mainly amongst fishermen, and whose venom characteristics and pathological mechanisms of the venom are poorly known. In the present study for the first time, we have characterized the main pathophysiological mechanisms associated with the clinical manifestation (pain, local inflammation and edema) of the envenomations caused by P. maculatus crude venom. It was estimated that the crude venom of one P. maculatus stinger contains approximately 100 μg of protein, likely the quantity involved in the envenomation. P. maculatus crude venom induced marked nociceptive and edematogenic effects and caused vascular permeability alterations at doses from 30 to 100 μg/animal. Additionally, P. maculatus crude venom caused a decrease in the contraction force in in situ frog heart, did not cause hemorrhage or alterations in clotting times (prothrombin time and activated partial thromboplastin time), but induced significant changes in the levels of CK and its isoenzyme CK-MB in mice. In the present work, we present a correlation between the effects obtained experimentally and the main symptoms observed in the human accidents provoked by P. maculatus.
The ability of venom-derived peptides to disrupt physiological processes in mammals provides an exciting source for pharmacological development. Our research group has identified a new class of neuroactive peptides from the venom of a Brazilian social wasp, Polybia occidentalis, with the potential pharmacological profile to treat epilepsies.
The study was divided into five phases: Phase 1 concerned the extraction, isolation, and purification of Occidentalin-1202(n) from the crude venom, followed by synthesis of an identical analog peptide, named Occidentalin-1202(s). In phase 2, we described the effects of both peptides in two acute models of epilepsy – Kainic acid and pentylenetetrazole-induced model of seizures – and measured estimated ED50 and therapeutic index (TI) values, electroencephalographic studies, and C-fos evaluation. Phase 3 was a compilation of advanced tests performed with Occidentalin-1202(s) only, reporting histopathological features and its performance in the pilocarpine-induced Status epilepticus (SE). After determination of antiepileptic activity of Occidentalin-1202(s), phase 4 consisted of evaluating its potential adverse effects, after chronic administration, on motor coordination (Rotarod) and cognitive impairment (Morris water maze) tests. Finally, in phase 5, we proposed a mechanism of action using computational models with kainate receptors.
The new peptide was able to across de blood brain barrier and showed potent antiseizure effects in acute (kainic acid and pentylenetetrazole) and chronic (Temporal Lobe Epilepsy model induced by pilocarpine) models. Motor and cognitive behavior were not adversely affected, and a potential neuroprotective effect was observed. Occidentalin-1202 can be a potent blocker of kainate receptor, as assessed by computational analysis, preventing glutamate and kainic acid from binding to the receptor's active site.
Occidentalin-1202 is a peptide with promising applicability to treat epilepsy and can be considered an interesting drug model for the development of new medicines.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.