Synthesis, radioprotective activity and pharmacokinetics characteristic of a new stable nitronyl nitroxyl radical-NIT2011
Synthesis, radioprotective activity and pharmacokinetics characteristic of a new stable nitronyl nitroxyl radical-NIT2011
复制标题
新型稳定硝酰基硝酰自由基-NIT2011的合成、辐射防护活性和药代动力学特征。
DOI：
10.1016/j.biochi.2013.04.011
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发表时间：
2013-08-01
期刊：
影响因子：
3.9
通讯作者：
Sun, Xiaoli
中科院分区：
文献类型：
--
作者：
Wang, Haibo;Jia, Yujing;Sun, Xiaoli
合成了一种新的稳定的硝基氮氧自由基NIT2011，并对其进行了表征。研究了NIT2011的辐射防护作用和药代动力学特征。结果表明，当照射剂量为6.5Gy伽玛照射时，单纯照射组第30天的存活率为20%。用0.25、0.5和1.0 mmol/kgNIT2011处理小鼠，第30天的存活率分别为70%、80%和90%。经NIT2011预处理后，小鼠的脾细胞集落数、骨髓细胞数和骨髓细胞蛋白质水平均增加。照射前预先给予NIT2011可提高血浆超氧化物歧化酶(SOD)活性。照射后24 h，单纯照射组小鼠血浆丙二醛水平为14.8+/-2.8nmol/m L，NIT2011(1 mm o l/kg)组小鼠血浆丙二醛水平为9.8+/-2.0nm o l/m L。照射后3d，单纯照射组小鼠的微核率为40.2+/-3.6，NIT2011(1 mmol/kg)组小鼠的微核率为11.7+/-1.2。NIT2011经口给药后易在小鼠体内吸收。与腹腔注射相比，NIT2011在小鼠体内的相对生物利用度为27.5%。NIT2011的LD_(50)为1510 mg/L
A new stable nitronyl nitroxyl radical NIT2011 was synthesized and characterized. The radioprotective effect and pharmacokinetics profiles of NIT2011 were investigated. The results showed that when irradiation exposure dose was 6.5 Gy gama radiation, the survival rate in the irradiation-only group was 20% on 30th day. The survival rate was 70%, 80%, and 90% on 30th day when mice were pretreated with 0.25, 0.5 and 1.0 mmol/kg NIT2011, respectively. The pretreatment of NIT2011 increased number of spleen colonies, the numbers of bone marrow cells and protein level in bone marrow cells. Pretreatment with NIT2011 prior to radiation exposure increased the plasma SOD (superoxide dismutase) activity. 24 h after irradiation exposure, level of plasma MDA (malondialdehyde) in irradiation-only mice was 14.8 +/- 2.8 nmol/mL, level of plasma MDA in NIT2011 (1 mmol/kg) pretreated mice was 9.8 +/- 2.0 nmol/mL. Three days after irradiation exposure, the micronucleus ratio in irradiation-only mice is 40.2 +/- 3.6, the micronucleus ratio in NIT2011 (1 mmol/kg) pretreated mice was 11.7 +/- 1.2. NIT2011 was easily absorbed in mice after it was oral administrated. Compared with the intraperitoneal injection, the relative oral bioavailability of the NIT2011 was 27.5% in mice. The LD50 of NIT2011 was 1510 mg/l