dinoprost and hydroquinone

Platelets play crucial roles in thrombosis and hemostasis through platelet activation and aggregation that are crucial in cardiovascular diseases. Hydroquinone (HQ) and its derivatives are present in many dermatological creams, paints, motor fuels, air, microorganisms, and plant products like wheat bread, fruit, coffee, and red wine. The effect of HQ on humans is not clear. In this study, we found that HQ (>25 μM) inhibited arachidonic acid (AA)-induced platelet aggregation. HQ suppressed AA-induced thromboxane B2 production of platelets. HQ (>10 μM) also attenuated ex vivo platelet-rich plasma aggregation. HQ prevented the interleukin (IL)-1β-induced 8-isoprostane, and PGE2 production, but not IL-8 production of pulp cells. These results indicate that HQ may have an antiplatelet effect via inhibition of thromboxane production. HQ has antioxidative and anti-inflammatory effects, and possible inhibition of COX. Exposure and consumption of HQ-containing products, food or drugs may have antiplatelet, antioxidative, and anti-inflammatory effects.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Blood Platelets; Cells, Cultured; Cyclooxygenase 2; Dental Pulp; Dinoprost; Dinoprostone; Humans; Hydroquinones; Inflammation Mediators; Interleukin-8; Mice; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Signal Transduction; Thromboxane A2

We examined whether arachidonoyl CoA (AA-CoA) can be a possible supplier of arachidonic acid (AA) for prostaglandin (PG) synthesis in rabbit kidney medulla. AA-CoA was preincubated with or without the 105,000 g supernatant (cytosol) fraction from the kidney medulla for 5 min at 37 degrees C followed by the incubation with the microsomal fraction (0.5 mg protein) (a rich source of PG synthesizing enzymes) in the presence of reduced glutathione and hydroquinone for 5 min at 37 degrees C, and the formed PGE2, F2 alpha and D2 were measured by high-pressure liquid chromatography using 9-anthryldiazomethane for derivatization. The addition of AA-CoA (20 nmol) alone changed the total PG formation (the sum of PGE2, F2 alpha and D2) from 0.14 to 1.55 ng. When the cytosolic fraction (10-100 microliters) was added together with 20 nmol-AA-CoA in the preincubation mixture, total PG formation was further increased 2- to 3-fold compared to AA-CoA alone. Experiments utilizing AA, instead of AA-CoA and boiled cytosolic fraction revealed that the stimulatory action of the cytosolic fraction on the AA-CoA-induced PG synthesis may not be due to the effect on cyclooxygenase activity and due to long-chain acyl CoA hydrolase. These results show that long-chain acyl CoA hydrolase which hydrolyzes AA-CoA to AA is present in the cytosol of rabbit kidney medulla and suggest that this enzyme activity is a potential mediator of supply of AA for PG synthesis in this region.

Topics: Acyl Coenzyme A; Animals; Arachidonic Acid; Chromatography, High Pressure Liquid; Cytosol; Dinoprost; Dinoprostone; Glutathione; Hydroquinones; Kidney Medulla; Male; Microsomes; Prostaglandin D2; Prostaglandins; Rabbits

Experiments were designed to study the interaction of rat peritoneal neutrophils with the vascular smooth muscle of the rat aorta. Rings of aorta, suspended in 10-ml organ chambers containing a physiologic salt solution, were precontracted with phenylephrine. Neutrophils (1 X 10(5) -4 X 10(7) cells/organ chamber) caused a cell number-dependent relaxation of the rat aorta that was augmented by superoxide dismutase (100 U/ml) or changing the oxygen content from 95 to 21%. The neutrophil-induced smooth muscle relaxation occurred in rings with and without endothelium and in rings precontracted with increasing concentrations of phenylephrine, prostaglandin F2 alpha or KCI. Catalase (1000 U/ml) and mannitol (1 X 10(-3) M) did not block the neutrophil-induced relaxation, whereas phenazine methosulfate (1 X 10(-5) M), hydroquinone (3 X 10(-5) M) and methylene blue (1 X 10(-5) M) reversed the neutrophil-induced relaxation. Pre-exposure of endothelium-rubbed rings to neutrophils (2 X 10(7) cells/organ chamber; 15 min) depressed the subsequent concentration-response curve to phenylephrine but augmented the relaxation induced by the phosphodiesterase inhibitor zaprinast (1 X 10(-5) M). The effluent from a column restraining the neutrophils induced a relaxation of endothelium-rubbed aortic rings that was prevented by methylene blue (1 X 10(-5) M). These results demonstrate that rat neutrophils release a factor that has a pharmacologic profile similar to that previously reported for the relaxing factor released from the vascular endothelium.

Topics: Animals; Biological Products; Catalase; Culture Techniques; Dinoprost; Endothelium, Vascular; Hydroquinones; Male; Mannitol; Methylene Blue; Methylphenazonium Methosulfate; Muscle, Smooth, Vascular; Neutrophils; Nitric Oxide; Phenylephrine; Potassium Chloride; Prostaglandins F; Rats; Rats, Inbred Lew; Superoxide Dismutase; Vasodilator Agents

We studied the prostaglandin (PG) synthetic capacity of microsomes of a relatively pure population of rabbit enterocytes and determined ideal conditions for product synthesis. The epithelial cells were freed from the basement membrane by a combination of calcium chelation and mechanical vibration, and 100,000 X g microsomes were prepared. These microsomes were found to synthesize PG from exogenously added arachidonic acid. The ideal conditions for the reaction were a microsomal protein concentration of 1.0 mg/ml, an arachidonic acid concentration of 33 uM, a reaction mixture pH of 8.0-9.5 and with epinephrine 1.5 mM added as a cofactor. The product yields increased linearly with time up to 30 min. of incubation and were inhibited by 100 uM indomethacin. Under the above ideal conditions enterocyte microsomes yielded the following products expressed as pmole/mg protein/20 min. incubation: PGF2 alpha 98 +/- 7, PGE2 48 +/- 9, PGD2 28 +/- 7, TxB2 40 +/- 5, 6 Keto PGF1 alpha 15 +/- 6.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Dinoprost; Epinephrine; Glutathione; Hydrogen-Ion Concentration; Hydroquinones; In Vitro Techniques; Indomethacin; Intestinal Mucosa; Intestine, Small; Male; Microsomes; Prostaglandins; Prostaglandins F; Rabbits