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Cardiotoxic activity of polymeric 3-alkylpyridinium salts from the marine sponge Reniera sarai
BMC Pharmacology volume 9, Article number: A62 (2009)
Marine sponges are a rich source of novel biologically active substances such as haemolytic proteins, hemagglutinins and proteins with antimicrobial, antiviral and antifungal activity. Toxic water-soluble polymeric 3-alkylpyridinum salts (poly-APS) have been isolated from the marine sponge Reniera sarai. Poly-APS has pore-forming properties expressed in a dose-dependent manner. These interactions with cell membranes results in increased Ca2+ permeability. In in vivo experiments performed in rats, poly-APS caused transient bradycardia, prolongation of expirium, lowered blood pressure, formed numerous thrombocyte aggregates and caused death. The aim of the present study was to investigate the direct cardiotoxic effects of poly-APS on isolated rat hearts.
Poly-APS isolated from the marine sponge Reniera sarai was purified and lyophilized. The experiments were carried out on the isolated rat hearts (Wistar rats, n = 30, weight 250-290 g) of both sexes according to Langendorff. The isolated rat hearts were perfused with different poly-APS concentrations (1, 10 and 100 nmol/L and 1 μmol/L). During the experiments, the coronary flow rate, lactate dehydrogenase (LDH) release rate, left ventricular pressure, heart rate and duration of arrhythmias were measured.
The most evident activity in all of the studied parameters was observed in the group perfused with poly-APS in a concentration of 1 μmol/L. Only the lowest concentration of poly-APS that was used (1 nmol/L) did not influence the measured parameters. Poly-APS in a concentration of 1 μmol/L diminished the coronary flow 7.6-fold, increased LDH release rate 12.7-fold, increased the pressure in left ventricle 2.6-fold and diminished heart rate 2.9-fold compared to the control group (all p < 0.001). Poly-APS also showed proarrhythmogenic activity.
Poly-APS salts isolated from the marine sponge Reniera sarai showed potent cardiotoxic activity on isolated rat hearts.
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Lunder, M., Žiberna, L., Sepčić, K. et al. Cardiotoxic activity of polymeric 3-alkylpyridinium salts from the marine sponge Reniera sarai. BMC Pharmacol 9 (Suppl 2), A62 (2009). https://doi.org/10.1186/1471-2210-9-S2-A62
- Release Rate
- Lactate Dehydrogenase
- Antifungal Activity
- Coronary Flow
- Lower Blood Pressure