In vivo toxic and lethal cardiovascular effects of a synthetic polymeric 1,3-dodecylpyridinium salt in rodents

Grandič, Marjana; Sepčić, Kristina; Turk, Tom; Juntes, Polona; Frangež, Robert

doi:10.1016/j.taap.2011.06.003

Cited by 14 publications

(15 citation statements)

References 22 publications

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“…At the end of each experiment, vital organs were removed for histological analysis. The estimated median lethal doses for APS12-2 and APS3 in mice were 11.5 and 7.25 mg/kg [8,42]. Compared to natural poly-APS, with an estimated LD 50 in rats of 2.7 mg/kg [24], the toxicity of APS12-2 and APS3 is low.…”

Section: Toxicity Of Aps12-2 and Aps3mentioning

confidence: 99%

“…Compared to natural poly-APS, with an estimated LD 50 in rats of 2.7 mg/kg [24], the toxicity of APS12-2 and APS3 is low. In in vivo experiments, it was found that rats are more sensitive to both analogues than mice [8,42]. …”

Section: Toxicity Of Aps12-2 and Aps3mentioning

confidence: 99%

“…The fact that no increase in heart beat frequency was observed during the period of transient hypertension supports this view. Sublethal doses of APS12-2 also caused significant elevation of blood potassium levels, which could be an important cause of the cardiorespiratory toxicity of APS12-2 [8]. …”

Section: Toxicity Of Aps12-2 and Aps3mentioning

confidence: 99%

“…In rats, the death caused by a lethal dose (11.5 mg/kg) of APS12-2 was due to cardiorespiratory arrest [8]. Since the latter can be produced at plasma potassium concentrations above 10 mM [43,44,45], the cardiotoxic effects of APS12-2 may be related to its hemolytic activity and hyperkalemia (10.44 ± 0.44 mM) [8,31].…”

Section: Toxicity Of Aps12-2 and Aps3mentioning

confidence: 99%

“…In water solutions, they form larger supramolecular aggregates [5,6,7]. However, recent analyses have indicated that poly-APS are composed of one monomeric species only, with a molecular weight of 5520 Da [8]. …”

Section: Introductionmentioning

confidence: 99%

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Pathophysiological Effects of Synthetic Derivatives of Polymeric Alkylpyridinium Salts from the Marine Sponge, Reniera sarai

Grandič

Frangež

2014

Marine Drugs

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Polymeric 3-alkylpyridinium salts (poly-APS) are among the most studied natural bioactive compounds extracted from the marine sponge, Reniera sarai. They exhibit a wide range of biological activities, and the most prominent among them are the anti-acetylcholinesterase and membrane-damaging activity. Due to their membrane activity, sAPS can induce the lysis of various cells and cell lines and inhibit the growth of bacteria and fungi. Because of their bioactivity, poly-APS are possible candidates for use in the fields of medicine, pharmacy and industry. Due to the small amounts of naturally occurring poly-APS, methods for the synthesis of analogues have been developed. They differ in chemical properties, such as the degree of polymerization, the length of the alkyl chains (from three to 12 carbon atoms) and in the counter ions present in their structures. Such structurally defined analogues with different chemical properties and degrees of polymerization possess different levels of biological activity. We review the current knowledge of the biological activity and toxicity of synthetic poly-APS analogues, with particular emphasis on the mechanisms of their physiological and pharmacological effects and, in particular, the mechanisms of toxicity of two analogues, APS12-2 and APS3, in vivo and in vitro.

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Section: Toxicity Of Aps12-2 and Aps3mentioning

confidence: 99%