Investigation of Antioxidative Ability of Nicotinic acid-related Cpmpounds

烟酸相关化合物抗氧化能力的研究

• 批准号: 11660087
• 负责人: TAGUCHI Hiroshi
• 金额: $ 0.83万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11660087/
• 关键词: nicotinic acid-related compounds; niacin-related compounds; isonicotinic acid hydrazide; apoptosis induction; picolinic acid; cultured cells; antioxidative ability; cancer cells; ナイアシン関連化合物; がん細胞; 活性酸素; フローサイトメーター; ラジカル; ESR; HL-60; グルコース

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.

烟酸类化合物的新的生理和药学功能是抗氧化能力。并对这些化合物的抗氧化能力进行了研究。首先采用自旋捕集法结合电子自旋共振（ESR）研究了其清除羟自由基的能力。结果表明，异烟酸、异烟酰胺、烟酰肼、异烟酰肼、6-氨基烟酸、6-氨基烟酰胺、吡啶等化合物具有较强的抗氧化能力。即，用这些化合物处理HL-60细胞，然后用过氧化氢或叔丁基过氧化氢（tBHP）给予氧化应激，并使用二氯荧光素二乙酸酯（DCFH-DA）作为氧化应激的探针，通过流式细胞术测量细胞中的氧化状态。其结果是，过氧化氢处理后，烟酸酰肼有效地降低了氧化应激。另外，异烟酸酰肼在10 mM、1 mM时也有效，因此，可以说，烟酸酰肼和异烟酸酰肼作为抗氧化剂，除了在体外以外，在细胞内也有效。以上结果表明，烟酸酰肼和异烟酸酰肼对过氧化氢和tBHP诱导的细胞凋亡有不同的抑制作用，因此本文研究了烟酸酰肼和异烟酸酰肼对氧化应激诱导的细胞凋亡的影响。结果表明，这些化合物可抑制过氧化氢诱导的细胞凋亡。然而，这些化合物对tBHP诱导的细胞凋亡无效。