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Endogenous induction of nitrosamines

内源性诱导亚硝胺

基本信息

批准号：
05454611
负责人：
KOSAKA Hiroaki
金额：
$ 3.84万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454611/
关键词：
nitrosamine nitric oxide (NO)electron spin resonance oxygen saturation hemoglobin nitric oxide synthase ischemic-gamma perfusion allograft rejection 酸素飽和度 NO サイトカイン腫瘍壊死因子

项目摘要

To know whcther environmentally existing amins are involved in in vivo nitrosation during inflammation, we studied the effect of interleukin 1 (IL-1) tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) on NO production inrats by detecting NO-hemoglobin (HbNO) in their blood using ESR,since the extent of nitrosation paralleled with NO production. Either IL-1 or TNF alone, but not IFN-gamma alone stimulated NO-hemoglobin (HbNO) generation, demonstrating synorglstic character of both stimuli on NO production. Further, LPS and TNF in combination were more potent stimulator of HbNO production in rats than each alone. Addition of IFN-gamma to the LPS-treated rats increased the TNF release markedly. These suggest that the increase of TNF release by IFN-gamma plays a key role in LPS-trated rats with respect to NO generation. During these experiments, distinct three-line hyperfune structure of HbNO was present in venous blood but not in arterial blood. We cleared that the three-line hyperfine structure intensified lineally with the decrease of oxygen sturation of hemoglobin, but desappeared upon reoxygenation of hemoglobin. We also found that plasma nitrate increases and HbNO appears during rat focal cerebral inschemia and reperfusion. Furthere, we proved using stable isotope of nitrogen that NO generates from nitrovasodilator as a result of metabolism. If nitrosatable amins exist in the environment and if someone is lacking ascorbic acid he may be exposed to the threat of nitrosamine formation by the endogenous NO especially in the case of inflammation.

为了了解环境中存在的胺是否参与炎症过程中的体内亚硝化，我们通过使用ESR检测血液中的NO-血红蛋白（HbNO），研究了白介素1（IL-1）肿瘤坏死因子（TNF）和干扰素γ（IFN-γ）对大鼠NO产生的影响，因为亚硝化程度与NO产生平行。单独的IL-1或TNF，但单独的IFN-γ不能刺激NO-血红蛋白（HbNO）的产生，证明两种刺激对NO产生的协同特征。此外，LPS 和 TNF 联合使用比单独使用更能有效刺激大鼠 HbNO 的产生。向 LPS 处理的大鼠中添加 IFN-γ 显着增加了 TNF 的释放。这些表明，IFN-γ 增加的 TNF 释放在 LPS 治疗的大鼠中对于 NO 的产生起着关键作用。在这些实验中，HbNO 的独特三线超函数结构存在于静脉血中，但不存在于动脉血中。我们发现，三线超精细结构随着血红蛋白氧饱和度的降低而线性增强，但在血红蛋白复氧时消失。我们还发现在大鼠局灶性脑缺血和再灌注期间血浆硝酸盐增加并且出现HbNO。此外，我们使用稳定的氮同位素证明了硝基血管舒张剂因新陈代谢而产生一氧化氮。如果环境中存在亚硝胺，并且某人缺乏抗坏血酸，他可能会受到内源性一氧化氮形成亚硝胺的威胁，尤其是在炎症情况下。