Katz-Brull Rachel
Department of Radiology, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel.
The Wohl Institute for Translational Medicine, Hadassah Medical Organization, Jerusalem 9112001, Israel.
Biology (Basel). 2022 May 23;11(5):794. doi: 10.3390/biology11050794.
Nitrate, the inorganic anion NO, is found in many foods and is an endogenous mammalian metabolite, which is supplied mostly through the diet. Although much is known about the safety of sodium nitrate when given , methodological safety data on intravenous bolus injection of sodium nitrate to rodents are lacking. Recently, we have proposed a new use for nitrate, as a contrast agent for magnetic resonance imaging that will be metal free and leave no traces in the body and the environment further to the imaging examination. It was shown that a stable isotope-labelled analog of this ion (NO), in a sodium nitrate solution form and hyperpolarized state, produces a high magnetic resonance signal with prolonged visibility. Therefore, sodium nitrate was targeted for further preclinical development in this context. In the absence of methodological safety data on the potential effects of a high concentration sodium nitrate bolus intravenous injection into rodents, we carried out such an investigation in mice and rats ( = 12 of each, 6 males and 6 females in each group, altogether 24 animals). We show here that an intravenous bolus administration of sodium nitrate at a concentration of 150 mM and a dose of 51 mg/Kg does not lead to adverse effects in mice and rats. This is the first investigation of the tolerance of rodents to an intravenous injection of sodium nitrate.
硝酸盐，即无机阴离子NO，存在于许多食物中，是哺乳动物的内源性代谢产物，主要通过饮食摄入。尽管对于给予硝酸钠时的安全性已有很多了解，但缺乏关于向啮齿动物静脉推注硝酸钠的方法学安全性数据。最近，我们提出了硝酸盐的一种新用途，即作为磁共振成像的造影剂，这种造影剂将不含金属，在成像检查后不会在体内和环境中留下任何痕迹。结果表明，这种离子（NO）的稳定同位素标记类似物，以硝酸钠溶液形式且处于超极化状态时，会产生具有延长可见性的高磁共振信号。因此，在此背景下，硝酸钠被作为进一步临床前开发的目标。由于缺乏关于向啮齿动物静脉推注高浓度硝酸钠潜在影响的方法学安全性数据，我们在小鼠和大鼠中进行了此类研究（每组各12只，每组6只雄性和6只雌性，共24只动物）。我们在此表明，以150 mM的浓度和每千克51毫克的剂量静脉推注硝酸钠，不会对小鼠和大鼠产生不良影响。这是首次对啮齿动物对静脉注射硝酸钠的耐受性进行的研究。
