Investigation of Antioxidative Ability of Nicotinic acid-related Cpmpounds

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Novel physiological and pharmaceutical functions of nicotinic acid-related compounds are antioxidative ability. Then this ability of these compounds was searched. At first hydroxy radical scavenging ability was investigated by spin trapping method with electron spin resonance (ESR). As the results, its strong ability was found in isonicotinic acid, isonicotinamide, nicotinic acid hydrazide, isonicotinic acid hydrazide, 6-aminonicotinic acid, 6-aminonicotinamide, pyridine, etc. Secondly, antioxidative ability of these compounds in cell system was investigated. Namely, HL-60 cells were treated with these compounds, then oxidative stress was given with hydrogen peroxide or tert-butylhydroperoxide (tBHP), and oxidative state in the cells was measured with flow cytometry using dichlorofluorescein diacetate (DCFH-DA) as a probe for oxidative stress. As the results, oxidative stress was effectively reduced by nicotinic acid hydrazide after hydrogen peroxide treatment. And isonicotinic acid hydrazide was also effective at 10 mM and 1 mM.Therefore, it can be said that nicotinic acid hydrazide and isonicotinic acid hydrazide were effective as antioxidants in cells in addition to in vitro. From above results different effect were expected among both compounds in apoptosis induced by oxidative stress with hydrogen peroxide or tBHP.Accordingly the effect of nicotinic acid hydrazide and isonicotinic acid hydrazide on the apoptosis induced by oxidative stress was investigated. As the results, the apoptosis induced by hydrogen peroxide was suppressed by these compounds. However, these compounds were not effective for the apoptosis induced by tBHP.