Mechanisms of Toxicity of 3-Alkylpyridinium Polymers from Marine Sponge Reniera sarai

Abstract

Polymeric 3-alkylpyridinium salts (poly-APS) present in the marine sponge Reniera sarai show a broad spectrum of biological activities. They are lytic to erythrocytes and various other mammalian cells, enabling the transfection of the latter with alien DNA. Furthermore, they show inhibitory effects to marine bacteria and can inhibit fouling of micro-and macroorganisms to submerged surfaces. Finally, poly-APS act as potent cholinesterase inhibitors. The kinetics of acetylcholinesterase inhibition by poly-APS in vitro is complex and comprises several successive phases ending in irreversible inhibition of the enzyme. The latter is accounted for by aggregation and precipitation of the enzymeinhibitor complexes. Poly-APS are lethal to rats in concentrations above 2.7 mg/kg. Monitoring of the basic vital functions and histopathological analysis showed that the effects directly ascribable to acetylcholinesterase inhibition are only observed after application of lower concentrations of poly-APS. At higher concentrations, such effects were masked by other, more pronounced and faster developing lethal effects of the toxin, such as haemolysis and platelet aggregation.

Polymeric alkylpyridinium salts permit intracellular delivery of human Tau in rat hippocampal neurons: requirement of Tau phosphorylation for functional deficits

“…Its non-toxic dose range may be limited further owing to its mix in polymer length determining some of its biological properties [77][78][79] (including anticholinesterase activity at higher concentrations [80] and complex in vivo toxicity [2.7 mg/kg lethal in rats, [81]). Based on the localised detection of hTau within the CA1 stratum pyramidale and the preferential entry of both Luficier yellow and hTau into neurons in mixed cultures, it would appear that Tau loading more readily occurs in neurons and not glial cells.…”

Mini-review: Molecular mechanisms of antifouling compounds

“…The polymeric 3-alkylpyridinium salts (poly-APS) isolated from a Mediterranean sponge, Reniera sarai, can protect submerged surfaces from fouling by bacteria, fungi, microalgae, and barnacles Garaventa et al 2003;Chelossi et al 2006;Turk et al 2007). It has been suggested that poly-APS acts as a surfactant, binding to and causing lesions in the lipid cell membrane and thus causing the lysis of the microorganism (Turk et al 2007). Brominated metabolites, bastadins, extracted from the sponge Ianthella basta, inhibit the settlement of the cypris larvae of barnacles, probably by regulating the intracellularCa 2+ levels (Ortlepp et al 2007).…”

Special Issue on Marine Toxins

“…Leone and colleagues from Italy and the Russian Federation [ 1 ] provide an update on the molecular structure of endotoxins from marine Gram-negative bacteria, and discuss their potential as lead candidates in the development of novel drugs to prevent septic shock. Turk and colleagues from Slovenia [ 2 ] present the current status of the mechanisms of toxicity of 3-alkylpyridinium polymers isolated from the marine sponge Reniera sarai. Twiner and colleagues from Charleston, South Carolina [ 3 ] review recent advances on the chemistry of various azaspiracid analogs, the putative progenitor algal species, as well as in vitro and in vivo data on the toxicology to human health.…”