Kaviarasan S, Anuradha C V
Department of Biochemistry, Annamalai University, Annamalai Nagar, Tamil Nadu, India.
Pharmazie. 2007 Apr;62(4):299-304.
The present study investigates the hepatoprotective effect of fenugreek seed polyphenolic extract (FPEt) against ethanol-induced hepatic injury and apoptosis in rats. Chronic ethanol administration (6 g/kg/day x 60 days) caused liver damage that was manifested by the elevation of markers of liver dysfunction--aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin and gamma-glutamyl transferase (GGT) in plasma and reduction in liver glycogen. The effects on alcohol metabolizing enzymes such as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were studied and found to be altered in the alcohol-treated group. Ethanol administration resulted in adaptive induction of the activities of cytochrome p450 (cyt-p-450) and cytochrome-b5 (cyt-b5) and reduction in cytochrome-c-reductase (cyt-c-red) and glutathione-S-tranferase (GST), a phase II enzyme. Further, ethanol reduced the viability of isolated hepatocytes (ex vivo) as assessed by the trypan blue exclusion test and increased hepatocyte apoptosis as assessed by propidium iodide staining (PI). Treatment with FPEt restored the levels of markers of liver injury and mitigated the alterations in alcohol metabolizing and detoxification enzymes and the electron transport component cytochrome-c reductase. Increased hepatocyte viability and reduced apoptotic nuclei were observed in FPEt-treated rats. These findings demonstrate that FPEt acts as a protective agent against ethanol-induced abnormalities in the liver. The effects of FPEt are comparable with those of a known hepatoprotective agent, silymarin.
本研究调查了胡芦巴种子多酚提取物(FPEt)对乙醇诱导的大鼠肝损伤和细胞凋亡的肝保护作用。长期给予乙醇(6 g/kg/天×60天)导致肝脏损伤,表现为血浆中肝功能标志物——天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)、胆红素和γ-谷氨酰转移酶(GGT)升高,肝糖原减少。研究了对乙醇代谢酶如乙醇脱氢酶(ADH)和乙醛脱氢酶(ALDH)的影响,发现乙醇处理组这些酶发生了改变。给予乙醇导致细胞色素p450(cyt-p-450)和细胞色素b5(cyt-b5)活性适应性诱导,细胞色素c还原酶(cyt-c-red)和II相酶谷胱甘肽S-转移酶(GST)活性降低。此外,乙醇降低了分离的肝细胞(体外)的活力,这通过台盼蓝排斥试验评估,并且增加了肝细胞凋亡,这通过碘化丙啶染色(PI)评估。用FPEt治疗可恢复肝损伤标志物水平,减轻乙醇代谢和解毒酶以及电子传递成分细胞色素c还原酶的改变。在FPEt治疗的大鼠中观察到肝细胞活力增加和凋亡细胞核减少。这些发现表明FPEt可作为一种保护剂,对抗乙醇诱导的肝脏异常。FPEt的作用与已知的肝保护剂水飞蓟宾相当。