title: Polyamines detoxify the anticoagulant effect of acetaldehyde on prothrombin time.
abstract: Naturally occurring bioamines, such as putrescine, cadaverine, agmatine, spermidine, and spermine, were tested at pharmacological levels for their capacity to affect prothrombin time (PT). Each of the bioamines tested prolonged PT with decreasing orders of sensitivity being agmatine > spermidine > spermine > putrescine > cadaverine. The respective millimolar concentrations, which exhibited prolongation in statistically significant concentrations were 1, 3, 3, 6, and 10 mM, respectively. Acetaldehyde (AcH) prolongs PT. Because amines react with AcH to form Schiff bases, the bioamines were tested for their potential to affect the prolongation of PT by AcH. It was observed that mixtures of each of the bioamines with AcH, upon preincubation at room temperature for 20 minutes before addition to plasma for a further 20 minutes (at room temperature), generated a major reduction in the prolongation of clotting time relative to that of AcH alone, thereby affecting a detoxication of AcH. Sequential addition of AcH first and bioamine second to plasma generally lowered prolongation of PT to a lesser extent. These results suggest that interaction of AcH, the highly reactive primary intermediate in the metabolism of ethanol, with bioamines may affect the physiological and pharmacological roles of the bioamines in vivo by diminishing the levels of free amines, in addition to affecting a detoxication of acetaldehyde.
authors.affiliation: Department of Chemistry, Bowling Green State University, Bowling Green, OH 43403, USA. artbrec@bgsu.edu
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Brecher
authors.forename: Anum H
authors.initials: AH
authors.lastname: Riaz
mesh_terms: D000079:Acetaldehyde / Q000633:toxicity*; D000925:Anticoagulants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000378:metabolism*; D006801:Humans; D011073:Polyamines / Q000008:administration & dosage / Q000494:pharmacology*; D011517:Prothrombin Time; D013696:Temperature; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D011073:Polyamines; D000431:Ethanol; D000079:Acetaldehyde