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| Background-In previous studies, the protection of reduced nicotinamide adenine dinucleotide phosphate (NADPH) on neurons against ischemia/reperfusion-induced injury was determined and its inhibition on platelet aggregation was found by accident. Here, the function of NADPH on platelet is explored deeply.
Methods and Results-In vitro studies, the effects of different concentrations of NADPH on platelet aggregation induced by ADP (10 μM), thrombin (0.05 U/mL) or AA (0.5 mM) were determined and we found that NADPH could concentration-dependently inhibit platelet aggregation induced by ADP or thrombin. When the inhibitory effects of NAD+, NADH, NADP+ and NADPH on platelet aggregation were compared, NADPH showed the best effect. In vivo studies, the effects between NADPH and aspirin on tail bleeding time, clotting time and ferric chloride-induced thrombosis model were compared in mice or rats. NADPH could prolong the tail bleeding times in mice, especially at 30 min after the injection of NADPH (7.5 mg/kg), while bleeding times in mice given aspirin (15 mg/kg) were significantly longer at any time point in 6 h. As we detected the influence of NADPH or aspirin on clotting times in rats, we found that both of them had no effect. Using a FeCl3-induced abdominal aorta injury thrombosis model, we found that the injection of NADPH provoked a significant time delay of vessel occlusion, while aspirin almost completely prevented the vessel occlusion. After we observed the injured vessel sections under the microscope, we discovered that the thrombi in injured vessel sections of rats injected NADPH were much looser than rats injected normal saline and the thrombi in injured vessel sections of rats given aspirin were fewest.
Conclusions-The current results suggest that NADPH can inhibit platelet aggregation and prevent hemostasis and thrombosis. To our knowledge, this is the first study on the effect of NADPH on platelet function. |
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| Keywords:Pharmacology; NADPH; platelet; thrombosis |
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