Rubber additives inhibit the calcium ionophore and thrombin induced activation of rabbit platelets

Abstract

Together with the mutagenic activities of 5 rubber vulcanization activators (tetramethylthiuram disulfide[TMTD], zinc dimethyldithiocarbamate[ZDMC], zinc diethyldithiocarbamate[ZDEC], sodium dimethyldithiocarbamate[SDMC] and sodium diethyldithiocarbamate[SDEC]), the effect of these compounds on thrombin or calcium ionophore A-23187 induced activation of washed rabbit platelets has been examined. The mutagenicity was investigated in Ames test, and platelet activation was measured by thromboxane B 2(TXB 2) synthesis and the amount of TXB 2 was determined by enzyme immunoassay (EIA). In mutagenic assay, TMTD, ZDMC and SDMC were mutagenic, on the other hand, all tested compounds inhibited the platelet activation induced by thrombin or A-23187 when they were added simultaneously. The thrombin induced platelet activation was inhibited in proportion to the increased concentration of rubber vulcanization activators. There was not so much IC 50 differences (2–4×10 −8M) between these compounds against the platelet activation by thrombin. For A-23187 induced platelet activation, the extent of inhibition by these compounds occurred independently of the concentrations used. When platelets were pretreated with these compounds for 5 min before stimulation with thrombin or A-23187, the decreased synthesis of TXB 2 was observed with all compounds. These inhibitory effects were not abolished after removal of the compounds. No correlations were observed between mutagenic activity and inhibitory effect of these rubber vulcanization activators.