Department of Pharmacology, El-Minia University, El-Minia, Egypt.
J Physiol Biochem. 2012 Mar;68(1):29-35. doi: 10.1007/s13105-011-0116-0. Epub 2011 Oct 11.
Liver fibrosis is a major health problem that can lead to the development of liver cirrhosis and hepatocellular carcinoma. On the other hand, several antioxidants have been shown to possess protective effect against liver fibrosis. Therefore, in the present work, the effectiveness of curcumin, α-lipoic acid, and N-acetylcysteine in protecting against carbon tetrachloride (CCl(4))-induced liver fibrosis as well as the mechanism(s) implicated in this protective effect was studied. The antioxidants used in this study resulted in hepatoprotective effect as evident by substantial decreases in collagen deposition in histopathological examinations in addition to significant decrease in serum levels of alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, bilirubin, and transforming growth factor-alpha (TGF-α) as well as hepatic malondialdehyde concentration, with a concurrent increase in serum matrix metalloproteinase-13 (MMP-13) and hepatic reduced glutathione (GSH) levels as compared to CCl(4) fibrotic group. In conclusion, curcumin, α-lipoic acid, and N-acetylcysteine protect rats against CCl(4)-induced liver fibrosis most possibly through their antioxidant activities and their capacities to induce MMP-13 and to inhibit TGF-α levels.
肝纤维化是一个主要的健康问题,可能导致肝硬化和肝癌的发展。另一方面,一些抗氧化剂已被证明对肝纤维化具有保护作用。因此,在本工作中,研究了姜黄素、α-硫辛酸和 N-乙酰半胱氨酸对四氯化碳(CCl4)诱导的肝纤维化的保护作用及其机制。本研究中使用的抗氧化剂具有肝保护作用,这一点在组织病理学检查中胶原沉积的大量减少中得到了证明,此外,丙氨酸氨基转移酶、天冬氨酸氨基转移酶、γ-谷氨酰转肽酶、胆红素和转化生长因子-α(TGF-α)的血清水平以及肝丙二醛浓度显著降低,同时血清基质金属蛋白酶-13(MMP-13)和肝还原型谷胱甘肽(GSH)水平升高,与 CCl4 纤维化组相比。总之,姜黄素、α-硫辛酸和 N-乙酰半胱氨酸通过其抗氧化活性及其诱导 MMP-13 和抑制 TGF-α水平的能力,可能对 CCl4 诱导的肝纤维化大鼠具有保护作用。