Nicotinic acid and pyridoxine modulate arachidonic acid metabolism in vitro and ex vivo in man

The in vitro effects of nicotinic acid (10-1000 mu M), pyridoxine (0.1-500 mu M) and pyridoxal-5'-phosphate (0.1500 mu M) and the ex vivo effects of n icotinic acid (2500 mg orally during 12 h) and pyridoxine (600 mg orally da ily for seven days) on arachidonic acid metabolism were investigated in cal cium ionophore A23187 (calcimycin)-stimulated human whole blood. In vitro n icotinic acid stimulated prostaglandin E-2 thromboxane B-2 and leukotriene E-4 synthesis. Pyridoxine at all concentrations and pyridoxal-5'-phosphate at the highest concentration stimulated prostaglandin E-2 and thromboxane B -2 production, but had no effect on leukotriene E-4 synthesis. Nicotinic ac id treatment increased ex vivo prostaglandin E-2, thromboxane B-2 and leuko triene E-4 synthesis to 185%, 165% and 175% of the initial values, respecti vely. In the pyridoxine-treated subjects, ex vivo prostaglandin E-2, thromb oxane B-2 and leukotriene E-4 synthesis was decreased after seven days to 7 5%, 65% and 45% of the initial values, respectively. In the present study t he effects of nicotinic acid on the 5-lipoxygenase pathway in arachidonic a cid metabolism were studied for the first time and the drug was found to st imulate this pathway in vitro and ex vivo. In vitro pyridoxine and pyridoxa l-5'-phosphate had no effect on the 5-lipoxygenase pathway. The inhibition of leukotriene synthesis by pyridoxine ex vivo might be of therapeutic impo rtance.