Mahéo K, Morel F, Antras-Ferry J, Langoüet S, Desmots F, Corcos L, Guillouzo A
INSERM Unité 456, Détoxication et Réparation Tissulaire, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I, Rennes, France.
Hepatology. 1998 Dec;28(6):1655-62. doi: 10.1002/hep.510280627.
The effect of Escherichia coli lipopolysaccharide (LPS), a classic inducer of the acute-phase response, has been analyzed on both constitutive and oltipraz (a chemoprotective agent)-inducible messenger RNAs (mRNAs) and enzyme activities of major cytochromes P450 (CYPs) and glutathione transferases (rGSTs) in rat liver. At the dose administered (1 mg/kg) and the time studied (6 and 24 hours), endotoxin had no effect on the expression of either CYPs and GSTs with the exception of CYP1A2, which was reduced at both mRNA and activity levels. A strong increase of rGSTA1/2, rGSTM1, rGSTP1, CYP1A2, CYP2B1/2, and CYP2E1 was observed after 3 days of treatment with oltipraz (0.075%, wt/wt). Oltipraz induction of these enzymes (with the exception of CYP2E1) was found to be suppressed at both mRNA, protein, and activity levels during the acute-phase response to endotoxin. Moreover, it is shown that oltipraz induction of CYP1A2 and CYP2B1/2 and its suppression by E. coli LPS occurred at a transcriptional level. These data support the idea that the chemoprotective effect of oltipraz is altered in the course of inflammation and that adaptation in chemoprotective strategies should be considered in certain physiopathologic situations.
已在大鼠肝脏中分析了急性期反应的经典诱导剂大肠杆菌脂多糖（LPS）对主要细胞色素P450（CYPs）和谷胱甘肽转移酶（rGSTs）的组成型及oltipraz（一种化学保护剂）诱导型信使核糖核酸（mRNAs）和酶活性的影响。在所给予的剂量（1 mg/kg）和所研究的时间（6小时和24小时）下，内毒素对CYPs和GSTs的表达没有影响，但CYP1A2除外，其mRNA和活性水平均降低。在用oltipraz（0.075%，重量/重量）处理3天后，观察到rGSTA1/2、rGSTM1、rGSTP1、CYP1A2、CYP2B1/2和CYP2E1有强烈增加。发现在对内毒素的急性期反应期间，这些酶（CYP2E1除外）的oltipraz诱导在mRNA、蛋白质和活性水平均受到抑制。此外，研究表明，oltipraz对CYP1A2和CYP2B1/2的诱导及其被大肠杆菌LPS的抑制发生在转录水平。这些数据支持这样一种观点，即oltipraz的化学保护作用在炎症过程中会发生改变，并且在某些生理病理情况下应考虑化学保护策略的适应性。
