Department of Biochemistry, Faculty of Science, Annamalai University, Annamalainagar608 002, India.
Toxicol Mech Methods. 2006;16(5):267-74. doi: 10.1080/15376520500194734.
Liver fibrosis is the result of imbalance between extracellular matrix (ECM) synthesis and breakdown. Ethanol-induced increase in redox state is a sign of major change in hepatic metabolism and this inhibits tricarboxylic acid cycle activity and, fatty acid oxidation and increases fatty acid uptake, thus predisposing fatty liver. Fibrotic changes induced by alcohol are provoked by diets rich in PUFA. Heating of oils rich in PUFA produces toxic volatile and nonvolatile compounds, which aggravate liver damage. Hepatotoxicity was induced in male Wistar rats by administering alcohol (20%) and thermally oxidized sunflower oil (Delta PUFA) (15%). When N-acetyl cyteine (NAC) (150 mg/kg body weight), an ROS scavenger, was administered, there was a reversal of liver damage, which was demonstrated biochemically. Matrix metalloproteinases (MMPs), being potential biochemical indicators of fibroproliferation, were estimated in the present study, which were found to be altered in alcohol, Delta PUFA, and alcohol + Delta PUFA. The altered activities of MMPs in these groups were effectively modulated by treatment with NAC. Thus, in this study, NAC was found to modulate the effect of alcohol and Delta PUFA-induced liver damage.
肝纤维化是细胞外基质（ECM）合成与分解失衡的结果。乙醇诱导的氧化还原状态增加是肝代谢重大变化的标志，这会抑制三羧酸循环活性、脂肪酸氧化并增加脂肪酸摄取，从而导致脂肪肝。酒精引起的纤维化变化是由富含多不饱和脂肪酸（PUFA）的饮食引发的。富含多不饱和脂肪酸的油加热会产生有毒的挥发性和非挥发性化合物，从而加重肝损伤。通过给雄性 Wistar 大鼠灌胃酒精（20%）和热氧化葵花籽油（Delta PUFA）（15%）诱导肝毒性。当给予 ROS 清除剂 N-乙酰半胱氨酸（NAC）（150mg/kg 体重）时，肝损伤得到逆转，这在生化上得到了证实。基质金属蛋白酶（MMPs）是纤维增生的潜在生化指标，本研究对其进行了评估，结果表明在酒精、Delta PUFA 和酒精+Delta PUFA 组中发生了改变。NAC 治疗有效调节了这些组中 MMPs 的活性。因此，在这项研究中，NAC 被发现可以调节酒精和 Delta PUFA 诱导的肝损伤的作用。
