Leonarduzzi G, Parola M, Muzio G, Garramone A, Maggiora M, Robino G, Poli G, Dianzani M U, Canuto R A
Dip. Medicina ed Oncologia Sper., Università degli Studi di Torino, Italy.
Biochem Biophys Res Commun. 1995 Sep 14;214(2):669-75. doi: 10.1006/bbrc.1995.2338.
4-Hydroxy-2,3-nonenal is a major aldehydic end-product of lipid peroxidation known to exert several biological and cytotoxic effects and to be produced during conditions of chronic cholestasis. Here we report that viable hepatocytes isolated from cholestatic livers of bile duct-ligated rats (BDL hepatocytes) show a significantly lower rate of HNE metabolism than control cells. This feature is likely to be the consequence of a significant inhibition in the activity of HNE-metabolizing cytosolic glutathione-S-transferase and alcohol dehydrogenase in BDL hepatocytes. Particulate NADP-dependent aldehyde dehydrogenase was also inhibited. No significant change was found for aldehyde reductase activity. A decreased hepatocellular metabolism of HNE can expose liver parenchymal and non-parenchymal cells to cytotoxic as well as pro-inflammatory and pro-fibrogenic effects of HNE, contributing to the development of chronic cholestatic liver damage.
4-羟基-2,3-壬烯醛是脂质过氧化的主要醛类终产物，已知其具有多种生物学和细胞毒性作用，并在慢性胆汁淤积的情况下产生。在此我们报告，从胆管结扎大鼠的胆汁淤积肝脏中分离出的有活力的肝细胞（BDL肝细胞）显示出比对照细胞显著更低的HNE代谢率。这一特征可能是BDL肝细胞中HNE代谢胞质谷胱甘肽-S-转移酶和乙醇脱氢酶活性受到显著抑制的结果。微粒体NADP依赖性醛脱氢酶也受到抑制。醛还原酶活性未发现显著变化。HNE肝细胞代谢的降低会使肝实质细胞和非实质细胞暴露于HNE的细胞毒性以及促炎和促纤维化作用之下，从而导致慢性胆汁淤积性肝损伤的发展。
