生物自旋捕集。II. 硝酮自旋捕集剂的毒性：大鼠剂量范围研究。

Biological spin trapping. II. Toxicity of nitrone spin traps: dose-ranging in the rat.

作者信息

Janzen E G, Poyer J L, Schaefer C F, Downs P E, DuBose C M

机构信息

National Biomedical Center for Spin Trapping and Free Radicals, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.

出版信息

J Biochem Biophys Methods. 1995 Nov;30(4):239-47. doi: 10.1016/0165-022x(95)00012-1.

DOI:10.1016/0165-022x(95)00012-1

PMID:8621883

Abstract

To obtain the strongest possible free radical spin adduct signal using the electron paramagnetic resonance spectroscopy-spin trapping technique, it is desirable to load an animal with the highest dose of spin trap possible. One hundred and twenty six male Sprague-Dawley rats were used to establish the toxic dose range for PBN (alpha-phenyl N-tert butyl nitrone) and 18 other similar spin traps. The lethal dose of PBN was found to be approximately 100 mg/100 g BW (0.564 mmol/100 g. The 18 other compounds were then tested, and their toxicities were gauged in terms of molar equivalents to PBN. Of these spin traps, DMPO (5,5-dimethyl-1-pyrroline-N-oxide) was found to be the least toxic (no toxic signs at twice the lethal dose for PBN) while 2,6-difluoro-PBN and M4PO (3,3,5,5-tetramethyl-1-pyrroline-N-oxide) were the most toxic, both causing death at one eighth the PBN-equivalent lethal dose. Nine of the 18 nitrones appeared non-toxic at the 0.25 PBN-equivalent lethal dose level.

摘要

为了使用电子顺磁共振光谱 - 自旋捕获技术获得最强的自由基自旋加合物信号，最好给动物注射尽可能高剂量的自旋捕获剂。126只雄性斯普拉格 - 道利大鼠用于确定PBN（α-苯基 -N-叔丁基硝酮）和其他18种类似自旋捕获剂的毒性剂量范围。发现PBN的致死剂量约为100mg / 100g体重（0.564mmol / 100g）。然后对其他18种化合物进行测试，并根据与PBN的摩尔当量来衡量它们的毒性。在这些自旋捕获剂中，DMPO（5,5 - 二甲基 -1-吡咯啉 -N-氧化物）被发现毒性最小（在PBN致死剂量的两倍时无毒性迹象），而2,6 - 二氟 -PBN和M4PO（3,3,5,5 - 四甲基 -1-吡咯啉 -N-氧化物）毒性最大，两者在相当于PBN致死剂量的八分之一时均导致死亡。18种硝酮中的9种在相当于PBN致死剂量0.25倍的水平时似乎无毒。