Inhibitory effect of chlormethiazole on the toxicokinetics of diethylnitrosamine in normal and hepatofibrotic rats
Inhibitory effect of chlormethiazole on the toxicokinetics of diethylnitrosamine in normal and hepatofibrotic rats
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氯甲噻唑对正常和肝纤维化大鼠二乙基亚硝胺毒代动力学的抑制作用
DOI：
10.1080/01480545.2018.1455204
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发表时间：
2019-11
期刊：
影响因子：
--
通讯作者：
Qiao Hai-Ling
中科院分区：
文献类型：
--
作者：
Wang Gao-Ju;Xiao Kang;Gao Jie;Jiang Shan;Wang Shang;Weng Shi-Jia;Xu Chen;Wang Tong;Qiao Hai-Ling
观察了氯甲唑(CMZ)单剂量和多剂量给药对正常大鼠和DEN肝纤维化大鼠体内二乙基亚硝胺(DEN)毒代动力学的影响。12只大鼠单次腹腔注射DEN(50 mg/kg)和单次注射CMZ(10、50、100 mg/kg)。注射。在多次给药实验中，6只大鼠连续给药7 (50 /kg)，第1、7天加入DEN(50 mg/kg)。12只大鼠腹腔注射DEN(50 mg/kg)。每周注射2次，连续4周，然后每周注射，连续注射8周，建立肝纤维化模型。诱导后12只大鼠同时给予环丙沙星(50 mg/kg)和DEN(50 mg/kg)，观察环丙沙星对肝纤维化大鼠DEN代谢的抑制作用。还收集了一系列血液样本，并用经过验证的高效液相色谱(HPLC)方法进行了分析。与未接受CMZ治疗的大鼠相比，单剂量CMZ治疗降低了正常和肝纤维化大鼠的DEN清除(CL)，延长了DEN的1/2，并增加了DEN的曲线下面积(AUC)。卡马西平治疗7 d后，DEN的潜伏期1/2进一步延长，但CL和AUC值与单药相比无明显变化。这些结果表明，CMZ对正常和肝纤维化大鼠的DEN代谢有明显的抑制作用。
The effect of chlormethiazole (CMZ) at single and multiple doses on the toxicokinetics of diethylnitrosamine (DEN) was investigated in normal rats and those with DEN-induced liver fibrosis. Twelve rats were treated with DEN (50 mg/kg) alone and in combination with a single dose of CMZ (10, 50, or 100 mg/kg) by intraperitoneal (i.p.) injection. In a multiple dose test, six rats were treated with CMZ (50 mg/kg) for 7 d with addition of DEN (50 mg/kg) on days 1 and 7. Lastly, 12 rats were treated with DEN (50 mg/kg) by i.p. injection twice a week for 4 consecutive weeks, followed by weekly injections for another 8 weeks to build the model of liver fibrosis. Following this induction, the 12 rats were given CMZ (50 mg/kg) combined with DEN (50 mg/kg) to study the inhibitory effect of CMZ on DEN metabolism in hepatofibrotic rats. Serial blood samples were also collected and analyzed by a validated high-performance liquid chromatography (HPLC) method. A single-dose CMZ treatment decreased DEN clearance (CL), prolonged thet1/2, and increased the ‘area under the curve’ (AUC) for DEN in normal and hepatofibrotic rats relative to rats that did not receive CMZ. Treatment with CMZ for 7 d further prolonged thet1/2for DEN but did not alter the CL and AUC relative to a single CMZ treatment. These results suggest that CMZ significantly inhibits the metabolism of DEN in normal and hepatofibrotic rats.
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影响因子：
--
作者：
Seitz, Helmut K;Wang, Xiang-Dong
通讯作者：
Wang, Xiang-Dong
影响因子：
9.7
作者：
K. Imaida;T. Shirai;M. Tatematsu;T. Takano;N. Ito
通讯作者：
K. Imaida;T. Shirai;M. Tatematsu;T. Takano;N. Ito
影响因子：
13.5
作者：
Lu, Yongke;Zhuge, Jian;Cederbaum, Arthur I.
通讯作者：
Cederbaum, Arthur I.
影响因子：
2.3
作者：
Dinis-Oliveira, Ricardo J.
通讯作者：
Dinis-Oliveira, Ricardo J.
影响因子：
5
作者：
Chang, Wei;He, Wei;Wei, Wei
通讯作者：
Wei, Wei