title: Toxic effects of head-to-tail 3-alkylpyridinium polymers isolated from the marine sponge Reniera sarai in rat.
abstract: Toxic water soluble polymeric 3-alkylpyridinium salts (poly APS; MW 18900 and 5520Da) were isolated from the marine sponge Raniera sarai. In vitro they strongly inhibited acetylcholinesterase. In order to evaluate the role of acetylcholinesterase inhibition in toxin lethality, and to assess other possible lethal effects, in vivo experiments were performed on male Wistar rats, and ECG, blood pressure and breathing pattern were monitored. The results showed that none of the animals died due to the acetylcholinesterase inhibitory action of poly-APS. Doses lower than 1mg/kg caused only transient bradycardia and transient prolongation of expirium. At doses above 2.7mg/kg of poly-APS all treated animals died, but signs were not typical of acetylcholinesterase inhibition. Arterial blood pressure fell to mid-circulatory pressure, and breathing stopped after a few breaths with an increase of the residual volume. Autopsy of the experimental animals that died due to the effects of the toxin revealed that mid-size and small sized blood vessels in the heart and lungs were filled with granular brownish material with inclusions of red blood cells and platelets. Data obtained on blood samples from animals treated with poly-APS also revealed numerous thrombocyte aggregates. In vitro poly-APS induced thrombocyte aggregation in a dose dependent manner. The acetylcholinesterase-inhibitory effects were most pronounced only at lower doses of poly-APS. With higher doses those effects were masked or covered by other, more pronounced and faster developing lethal effects of the toxin such as platelet aggregation. Therefore it is reasonable to assume that acetylcholinesterase inhibitory effects are not responsible for the lethal activity of the toxin.
authors.affiliation: Medical Faculty, Institute of Pathophysiology, Zaloska 4, 1104 Ljubljana, Slovenia.
authors.forename: Matjaz
authors.initials: M
authors.lastname: Bunc
authors.forename: Jerneja
authors.initials: J
authors.lastname: Strupi-Suput
authors.forename: Aleksander
authors.initials: A
authors.lastname: Vodovnik
authors.forename: Dusan
authors.initials: D
authors.lastname: Suput
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D001919:Bradycardia / Q000139:chemically induced; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D008136:Longevity / Q000187:drug effects; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D011108:Polymers / Q000008:administration & dosage / Q000633:toxicity*; D011161:Porifera / Q000737:chemistry*; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013990:Tidal Volume / Q000187:drug effects / Q000502:physiology; D018675:Toxicity Tests
chemical_list: D002800:Cholinesterase Inhibitors; D011108:Polymers; D011726:Pyridinium Compounds; C115254:poly-APS