Spin trapping of free radical metabolites of carbon tetrachloride in vitro and in vivo: effect of acute ethanol administration.
Spin trapping of free radical metabolites of carbon tetrachloride in vitro and in vivo: effect of acute ethanol administration.
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四氯化碳自由基代谢物的体外和体内自旋捕获：急性乙醇给药的影响。
DOI：
10.1016/0041-008x(92)90274-v
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发表时间：
1992
影响因子：
3.8
通讯作者：
Janzen,EG
中科院分区：
文献类型：
--
作者：
Reinke,LA;Towner,RA;Janzen,EG
在CCl 4之前18小时给予单剂量乙醇，可增强卤烃的肝毒性。在这些研究中，自旋捕获和电子自旋共振（ESR）光谱方法被用来确定是否一个单一的乙醇剂量增加代谢的四氯化碳自由基中间体。当乙醇处理或对照大鼠肝微粒体与CCl_4和自旋捕获剂α-苯基-N-叔丁基硝酮（PBN）孵育时，PBN的三氯甲基自由基加合物的ESR信号在两组中强度相似。乙醇剂量也未能诱导对硝基苯酚羟化酶活性。当PBN和CCl 4给药到大鼠，肝提取物中含有ESR信号主要来自PBN的三氯甲基自由基加合物，信号强度在两个实验组相似。较高浓度的二氧化碳阴离子自由基加合物的PBN检测乙醇处理大鼠的血浆样品。然而，当乙醇处理和对照大鼠的肝细胞与PBN和四氯化碳孵育时，二氧化碳加合物的ESR信号具有相似的强度。这些数据表明，较高浓度的二氧化碳加合物在血液中的乙醇处理的大鼠可以解释早期四氯化碳诱导的肝细胞膜损伤，而不是增加的形成率。本报告中的数据不支持单剂量乙醇刺激肝脏代谢CCl 4为三氯甲基自由基的假设。另外，乙醇可能通过影响三氯甲基自由基形成后的某些关键代谢步骤而增强四氯化碳的毒性。
A single dose of ethanol, when administered 18 hr prior to CCl4, potentiates the hepatotoxicity of the halocarbon. In these studies, spin trapping and electron spin resonance (ESR) spectroscopy methods were utilized to determine whether a single ethanol dose increased the metabolism of CCl4to free radical intermediates. When hepatic microsomes from ethanol-treated or control rats were incubated with CCl4and the spin trapping agent α-phenyl-N-tert-butylnitrone (PBN), the ESR signal of the trichloromethyl radical adduct of PBN was of similar intensity in both groups. The ethanol dose also failed to induce p-nitrophenol hydroxylase activity. When PBN and CCl4were administered to rats, liver extracts contained ESR signals resulting primarily from the trichloromethyl radical adduct of PBN, and the signals were of similar intensity in both experimental groups. Higher concentrations of the carbon dioxide anion radical adduct of PBN were detected in plasma samples from ethanol-treated rats. However, when hepatocytes from ethanol-treated and control rats were incubated with PBN and CCl4, ESR signals of the carbon dioxide adduct were of similar intensity. These data suggest that the higher concentrations of the carbon dioxide adduct in the blood of ethanol-treated rats may be explained by early CCl4-induced damage to liver cell membranes, rather than increased rates of formation. The data in this report fail to support the hypothesis that a single dose of ethanol stimulates the hepatic metabolism of CCl4to the trichloromethyl radical. Alternatively, ethanol may potentiate CCl4toxicity by affecting some critical metabolic step subsequent to trichloromethyl radical formation.
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通过体内质子磁共振成像（MRI）和电子显微镜（EM）检测苯基叔丁基硝酮（PBN）对CCl4诱导的大鼠肝损伤的影响。
DOI：
10.3109/10715769009145691
发表时间：
1990
期刊：
Free radical research communications
影响因子：
--
作者：
E. Janzen;R. Towner;S. Yamashiro
通讯作者：
S. Yamashiro
DOI：
10.1016/s0021-9258(17)38535-6
发表时间：
1986-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
H. Connor;R. Thurman;M. Galizi;R. Mason
通讯作者：
H. Connor;R. Thurman;M. Galizi;R. Mason
完整肝细胞中药物代谢的调节因素。
影响因子：
21.1
作者：
R. Thurman;F. Kauffman
通讯作者：
F. Kauffman
影响因子：
3.8
作者：
O. Strubelt
通讯作者：
O. Strubelt
卤烃引起的肝损伤的体内质子核磁共振成像和光谱学研究
影响因子：
3.3
作者：
M. Brauer;R. Towner;Ian Renaud;E. Janzen;D. Foxall
通讯作者：
D. Foxall