Brevenal Inhibits Pacific Ciguatoxin-1B-Induced Neurosecretion from Bovine Chromaffin Cells

Ciguatoxins and brevetoxins are neurotoxic cyclic polyether compounds produced by dinoflagellates, which are responsible for ciguatera and neurotoxic shellfish poisoning (NSP) respectively. Recently, brevenal, a natural compound was found to specifically inhibit brevetoxin action and to have a beneficial effect in NSP. Considering that brevetoxin and ciguatoxin specifically activate voltage-sensitive Na+ channels through the same binding site, brevenal has therefore a good potential for the treatment of ciguatera. Pacific ciguatoxin-1B (P-CTX-1B) activates voltage-sensitive Na+ channels and promotes an increase in neurotransmitter release believed to underpin the symptoms associated with ciguatera. However, the mechanism through which slow Na+ influx promotes neurosecretion is not fully understood. In the present study, we used chromaffin cells as a model to reconstitute the sequence of events culminating in ciguatoxin-evoked neurosecretion. We show that P-CTX-1B induces a tetrodotoxin-sensitive rise in intracellular Na+, closely followed by an increase in cytosolic Ca2+ responsible for promoting SNARE-dependent catecholamine secretion. Our results reveal that brevenal and β-naphtoyl-brevetoxin prevent P-CTX-1B secretagogue activity without affecting nicotine or barium-induced catecholamine secretion. Brevenal is therefore a potent inhibitor of ciguatoxin-induced neurotoxic effect and a potential treatment for ciguatera

A Novel Protein Kinase-Like Domain in a Selenoprotein, Widespread in the Tree of Life

Selenoproteins serve important functions in many organisms, usually providing essential oxidoreductase enzymatic activity, often for defense against toxic xenobiotic substances. Most eukaryotic genomes possess a small number of these proteins, usually not more than 20. Selenoproteins belong to various structural classes, often related to oxidoreductase function, yet a few of them are completely uncharacterised

Arterial compliance may be reduced by ingestion of red wine

The aim of this study was to assess the effect of alcohol on blood pressure and arterial compliance over 24 h in a group of volunteers, comparing the same group of subjects on two consecutive but separate days, one with alcohol intake (alcohol day) and one free of alcohol (control day). We studied 18 healthy subjects (mean age 34.2 years, range 25-53). The subjects received the two days in random order. On the alcohol day, the subjects were asked to drink two glasses of red wine (12% ethanol) between 1830 hours and 0430 hours. Measurements of heart rate, blood pressure and QKD interval (Q wave to Korotkoff (K) sound, diastolic phase (D) using Diasys Integra (Novacor, France)) were recorded (usually 1500 hours to 1500 hours). Three 'ingestion' periods were defined, from 1500 hours to 1830 hours ('before'), 1900 hours to 0430 hours ('during') and from 0430 hours to the following afternoon ('after') on both the alcohol day and on the control day. Red wine increased heart rate during alcohol ingestion and reduced arterial compliance after ingestion. The significant effect of interaction between day and ingestion period on heart rate, diastolic blood pressure and QKD were found, suggesting that the differences in response among the ingestion periods depended on whether alcohol has been consumed that day. For the first time our study indicates the effect of alcohol on 24 h arterial stiffness in a healthy group of volunteers.Journal of Human Hypertension advance online publication, 19 March 2015; doi:10.1038/jhh.2015.19