APS12-2 is one of a number of synthetic analogues of the polymeric alkylpyridinium salts from the marine sponge Reniera sarai. As it is a potential candidate for treating non small cell lung cancer, we have studied its possible toxic and lethal effects in a whole organism. The median lethal dose (LD50) of APS12-2 in mice was shown to be 11.5 mg/kg. Electrocardiograms, arterial blood pressure and respiratory activity were recorded under general anesthesia in untreated, pharmacologically vagotomized and artificially ventilated rats injected with APS12-2. In one group, the in vivo effects of APS12-2 were studied on nerve-evoked muscle contraction. Administration of APS12-2 at a dose of 8 mg/kg produced a progressive reduction of arterial blood pressure to a mid-circulatory value, accompanied by bradycardia, myocardial ischemia and ventricular extrasystoles, and second degree atrio-ventricular block. Similar electrocardiogram and arterial blood pressure changes caused by APS12-2 (8 mg/kg) were observed in animals pretreated with atropine and in artificially ventilated animals, indicating that hypoxia and cholinergic effects do not play a crucial role in the toxicity of APS12-2. Application of APS12-2 at sublethal doses (4 and 5.5 mg/kg) caused a decrease of arterial blood pressure, followed by increase slightly above control values. In addition, APS12-2 induced lysis of rat erythrocytes in vitro, and probably also in vivo since hyperkalemia and decreased hematocrit were observed. Hyperkalemia probably plays an important role in APS12-2 cardiotoxicity, since no evident changes in pathohistology of the heart were found.
COBISS.SI-ID: 3364218