thromboxane-a2 and 2-aminomethyl-4-t-butyl-6-iodophenol

Topics: Anti-Inflammatory Agents; Anticoagulants; Butylated Hydroxytoluene; Epoprostenol; Humans; Phospholipids; Platelet Aggregation; Prostaglandin Antagonists; Prostaglandins E; Prostaglandins F; Thromboxane A2; Vasodilator Agents

To investigate the effects of MK-447 on platelet shape change, aggregation, and ATP release by collagen (Col), ADP, and stable analogue of thromboxane A2 (STA2) in rabbits.. Platelet shape change and aggregation were quantified in light transmission by turbidimetric method and release reaction was assessed by the amount of ATP in platelet-rich plasma (PRP).. (1) MK-447 100-700 mumol.L-1 caused only the shape change, which was not inhibited by indometacin 3 mumol.L-1. Platelet shape changes by Col, ADP, and STA2 were reduced (P < 0.01) after the addition of MK-447. The lag phase was prolonged (P < 0.01) in Col and shortened (P < 0.01) in ADP. (2) MK-447 reduced the aggregation by Col 5 mg.L-1 (P < 0.01), and enhanced that by ADP 0.3-10 mumol.L-1 and STA2 0.1-3 mumol.L-1 (P < 0.01). (3) The release reaction by STA2 1-3 mumol.L-1 was also increased (P < 0.01). The effects of MK-447 on STA2 were not inhibited by S-145.. MK-447 induced the platelet shape change, and showed the dual effects, inhibition or enhancement, on the actions by different aggregating agents.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Platelets; Butylated Hydroxytoluene; Collagen; Platelet Aggregation; Rabbits; Thromboxane A2

The effects of phenolic anti-inflammatory drug, MK-447, on prostaglandin (PG) I2 and thromboxane (TX) A2 biosynthesis by rat dental pulp tissue were evaluated in the presence of 10 mM mannitol (MA) or 1 mM ascorbic acid with 0.3 mM Fe2+ (A + F). Although MK-447 alone at 1 and 10 microM had no significant effects, MK-447 at 100 microM stimulated both PGI2 and TXA2 biosynthesis, and suppressed the lipid peroxidation in the pulp tissue as estimated by thiobarbituric acid method. MA also reduced the lipid peroxidation, but had no effect on PG and TX production. However, in the presence of MA, the stimulatory effect of MK-447 was potentiated, and the significant effects were observed at concentrations higher than 1 microM. In contrast, A + F remarkably stimulated the lipid peroxidation, and inhibited both PG and TX biosynthesis. In the presence of A + F, MK-447 showed no stimulatory effect, and contrary, at 100 microM inhibited PG and TX production. These results suggest that the cellular levels of lipid peroxidation exert a significant influence on the effects of phenolic anti-inflammatory drugs like MK-447 on PG biosynthesis. The possible mechanism of action for such drugs has been discussed in view of the significance of lipid peroxidation in inflammatory condition.

Topics: Animals; Anti-Inflammatory Agents; Ascorbic Acid; Butylated Hydroxytoluene; Dental Pulp; Ferrous Compounds; In Vitro Techniques; Lipid Peroxides; Male; Mannitol; Prostaglandins; Rats; Rats, Inbred Strains; Thromboxane A2