Inhibition of human and rabbit platelet aggregation by chlorophenoxyacid herbicides.
Inhibition of human platelet aggregation by eight chlorophenoxyacid herbicides was studied in vitro. Thrombocyte aggregation in the platelet-rich plasma was induced by 1.0-32.0 microM adenosine diphosphate (ADP), 0.32-32.0 microM adrenaline or 7.5-30.0 micrograms/ml collagen with and without chlorophenoxyacid (0.05-2.0 mg/ml). Platelet aggregation by each inducer was inhibited dose dependently by all the eight chlorophenoxyacids at concentrations between 0.1 and 2.0 mg/ml. Increasing the concentrations of ADP and collagen but not of adrenaline inhibited the antiaggregatory action of chlorophenoxy-acids. No essential differences in inhibitory effect were found between different chlorophenoxyacids varying in respect of their ring substituents and the length of the carboxylic side chain. In the platelet-rich plasma prepared from rabbits 2.5 h after subcutaneous injection of 2.4-dichlorophenoxyacetic acid or 4-chloro-2-methylphenoxyacetic acid (100-150 mg/kg), platelet aggregation by ADP was inhibited 20-30%, compared to plasma taken from the rabbits before the chlorophenoxyacid treatment. The inhibition had disappeared by 20-23 h after administration. The results indicate that chlorophenoxyacid herbicides inhibit human platelet aggregation. Furthermore, the inhibition is probably involved in haemorrhages known to occur in various tissues of animals intoxicated by chlorophenoxyacid herbicides.
Elo
H A
HA
Department of Pharmaceutical Chemistry, University of Kuopio, Finland.
Luoma
T
T
Ylitalo
P
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D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000633:toxicity; D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity; D000085:Acetates / Q000633:toxicity*; D000328:Adult; D000818:Animals; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013928:Thromboxane A2 / Q000502:physiology
D000085:Acetates; D006540:Herbicides; D010975:Platelet Aggregation Inhibitors; D015084:2,4-Dichlorophenoxyacetic Acid; D013928:Thromboxane A2; D003094:Collagen; D015085:2,4,5-Trichlorophenoxyacetic Acid