A Kinder Side of Red Tides?

Investigators conducting a decade-long study into how Florida's " red tide " algal blooms affect human health have discovered several compounds that counteract the toxins produced by the red tide dinoflagellate, Karenia brevis. In an intriguing twist, they are now developing one of these compounds, breve-nal, as a potential treatment for cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). In cellular and animal models brevenal appears far more potent than existing drugs for CF and COPD and exhibits the unique quality of both suppressing inflammation and boosting mucociliary clearance. The investigators spent five years identifying compounds produced by K. brevis that cause classic red tide symptoms of broncho-constriction, watering eyes, and slowed mucociliary clearance. " Then we expanded the study to characterize all the degradation products, the side products, and coproducts from the biosynthetic machinery that could also be airborne, as we thought these might have some effect on people, " says To the investigators' surprise, three compounds actually mitigated the classical red tide toxicities. That seemed to explain a theretofore baffling observation: at certain times during a bloom, red tide toxicities appear to abate despite K. brevis' abundance in the waters, Baden says. The most promising of these compounds is brevenal. 2 In cellular and sheep models, brevenal is therapeutically active at nanogram to picogram concentrations. In comparison, amiloride and glucocorticoster-oids, used to treat CF and COPD, are active at microgram to milligram doses. Moreover, even the highest doses of brevenal tested caused no sign of irritation in the airways or other toxicity, says investigator William Animal tests showed the compound had two effects that Abraham says are especially useful in diseases where there is impaired mucus clearance. First, it stimulated normal mucociliary clearance. Second, it blocked the mucociliary-slowing effect of human neutrophil elastase administered to the animals. Neutrophil elastase, an immune mediator, is often overproduced in respiratory diseases such as COPD and CF, making mucus thick and sticky. " The newest [unpublished] information we have is that brevenal reduces the recruitment of neutrophils to the airway in response to elastase, making brevenal a molecule that has both mucociliary and antiinflammatory activity, " Abraham says. Baden says brevenal interacts with a previously undescribed therapeutic target. 4 It is also the only known example of an algal compound that counteracts toxins produced by the same microorganism , according to Michael Twiner, an assistant professor of biology in the University …