Introduction to the Theme “Old and New Toxicology: Interfaces with Pharmacology”

The theme of Volume 61 is “Old and New Toxicology: Interfaces with Pharmacology.” Old toxicology is exemplified by the authors of the autobiographical articles: B.M. Olivera's work on toxins and venoms from cone snails and P. Taylor's studies of acetylcholinesterase and the nicotinic cholinergic receptor, which serve as sites of action for numerous pesticides and venoms. Other articles in this volume focus on new understanding and new types of toxicology, including ( a) arsenic toxicity, which is an ancient poison that, through evolution, has caused most multicellular organisms to express an active arsenic methyltransferase to methylate arsenite, which accelerates the excretion of arsenic from the body; ( b) small molecules that react with lipid dicarbonyls, which are now considered the most toxic oxidative stress end products; ( c) immune checkpoint inhibitors (ICIs), which have revolutionized cancer therapy but have numerous immune-related adverse events, including cardiovascular complications; ( d) autoimmunity caused by the environment; ( e) idiosyncratic drug-induced liver disease, which together with the toxicity of ICIs represents new toxicology interfacing with pharmacology; and ( f) sex differences in the development of cardiovascular disease, with men more susceptible than women to vascular inflammation that initiates and perpetuates disease. These articles and others in Volume 61 reflect the interface and close integration of pharmacology and toxicology that began long ago but continues today.

Encapsulation of neurotoxins - blockers of nicotinic acetylcholine receptors - in nanomaterials based on sulfated polysaccharides

The three-finger snake neurotoxins are selective antagonists of some nicotinic cholinergic receptor subtypes and are used to study these receptors. The peptide neurotoxin azemiopsin, recently isolated from the venom of Azemipos feae, is a selective muscle-type cholinergic receptor blocker. In order to reduce their toxicity and increase resistance under physiological conditions, we have encapsulated these toxins into nanomaterials. The study of nanomaterials after interaction with neurotoxins by the methods of transmission electron microscopy and dynamic light scattering revealed an increase in the size of nanoparticles, which indicates the inclusion of neurotoxins in nanomaterials.

Arginine Vasopressin Injected into the Dorsal Motor Nucleus of the Vagus Inhibits Gastric Motility in Rats

Background. Until now, the effect of arginine vasopressin (AVP) in the DMV on gastric motility and the possible modulating pathway between the DMV and the gastrointestinal system remain poorly understood.Objectives. We aimed to explore the role of AVP in the DMV in regulating gastric motility and the possible central and peripheral pathways.Material and Methods. Firstly, we microinjected different doses of AVP into the DMV and investigated its effects on gastric motility in rats. Then, the possible central and peripheral pathways that regulate gastric motility were also discussed by microinjectingSR49059(a specific AVP receptor antagonist) into the DMV and intravenous injection of hexamethonium (a specific neuronal nicotinic cholinergic receptor antagonist) before AVP microinjection.Results. Following microinjection of AVP (180 pmol and 18 pmol) into the DMV, the gastric motility (including total amplitude, total duration, and motility index of gastric contraction) was significantly inhibited (P<0.05). Moreover, the inhibitory effect of AVP (180 pmol) on gastric motility could be blocked completely by bothSR49059(320 pmol) and hexamethonium (8 μmol).Conclusions. It is concluded that AVP inhibits the gastric motility by acting on the specific AVP receptor in the DMV, with the potential involvement of the parasympathetic preganglionic cholinergic fibers.