Al-Basher Gadah I
Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Saudi J Biol Sci. 2019 Mar;26(3):531-540. doi: 10.1016/j.sjbs.2017.08.007. Epub 2017 Aug 18.
Iron overload toxicity was shown to associate with chronic liver diseases which lead to hepatic fibrosis and subsequently the progression to cancer through oxidative stress and apoptotic pathways. Green tea potential activity as chelating, anti-oxidative, or anti-apoptotic mechanisms against metal toxicity was poorly clarified. Here, we are trying to evaluate the anti-oxidant and anti-apoptotic properties of green tea in the regulation of serum hepcidin levels, reduction in iron overloads, and improve of liver fibrosis in iron overloaded experimental rats. Three groups of male adult rats were randomly classified into three groups and treated as follows: control rats, iron treated rats for two months in drinking water followed by either vehicle or green tea extract (AGTE; 100 mg/kg) treatment for 2 more months. Thereafter, we studied the effects of AGTE on iron overload-induced lipid peroxidation, anti-oxidant depletion, liver cell injury and apoptosis. Treatment of iron-overloaded rats with AGTE resulted in marked decreases in iron accumulation within liver, depletion in serum ferritin, and hepcidin levels. Iron-overloaded rats had significant increase in malonyldialdehyde (MDA), a marker of lipid peroxidation and nitric oxide (NO) in liver when compared to control group. Also, significant change in cytochrome c and DNA content as apoptotic markers were reported in iron treated rats. The effects of iron overload on lipid peroxidation, NO levels, cytochrome c and DNA content were significantly reduced by the intervention treatment with AGTE (P < 0.001). Furthermore, the endogenous anti-oxidant capacities/levels (TAC) in liver were also significantly decreased in chronic iron overload and administration of AGTE restored the decrease in the hepatic antioxidant activities/levels. Also, hepatic hepcidin was shown to be significantly correlated with oxidative and apoptotic relating biomarkers as well as an improvement in liver fibrosis of iron treated rats following AGTE treatment. In-vitro analysis showed that, the improvement in iron toxicity of the liver depend mainly on antioxidant and protective ability of green tea polyphenolic compounds especiallyepigallocatechin-3-gallate (EGCG). Our study showed that green tea extract (GTE) ameliorates iron overload induced hepatotoxicity, apoptosis and oxidative stress in rat liver via inhibition of hepatic iron accumulation; improve of liver antioxidant capacity, and down regulation of serum hepcidin as well as reduction in the release of apoptotic relating proteins.
铁过载毒性与慢性肝病相关，慢性肝病会导致肝纤维化，随后通过氧化应激和凋亡途径发展为癌症。绿茶作为螯合剂、抗氧化剂或抗凋亡剂对抗金属毒性的潜在活性尚未得到充分阐明。在此，我们试图评估绿茶在调节血清铁调素水平、降低铁过载以及改善铁过载实验大鼠肝纤维化方面的抗氧化和抗凋亡特性。将三组成年雄性大鼠随机分为三组并进行如下处理：对照组大鼠；铁处理大鼠，在饮用水中给予铁剂两个月，之后分别给予赋形剂或绿茶提取物（AGTE；100mg/kg）再处理两个月。此后，我们研究了AGTE对铁过载诱导的脂质过氧化、抗氧化剂消耗、肝细胞损伤和凋亡的影响。用AGTE处理铁过载大鼠导致肝脏中铁积累显著减少、血清铁蛋白和铁调素水平降低。与对照组相比，铁过载大鼠肝脏中脂质过氧化标志物丙二醛（MDA）和一氧化氮（NO）显著增加。此外，铁处理大鼠中细胞色素c和DNA含量作为凋亡标志物也有显著变化。AGTE干预处理显著降低了铁过载对脂质过氧化、NO水平、细胞色素c和DNA含量的影响（P<0.001）。此外，慢性铁过载时肝脏内源性抗氧化能力/水平（TAC）也显著降低，给予AGTE可恢复肝脏抗氧化活性/水平的下降。此外，肝脏铁调素与氧化和凋亡相关生物标志物显著相关，并且AGTE处理后铁处理大鼠的肝纤维化有所改善。体外分析表明，肝脏铁毒性的改善主要取决于绿茶多酚化合物尤其是表没食子儿茶素-3-没食子酸酯（EGCG）的抗氧化和保护能力。我们的研究表明，绿茶提取物（GTE）通过抑制肝脏铁积累、提高肝脏抗氧化能力、下调血清铁调素以及减少凋亡相关蛋白的释放，改善铁过载诱导的大鼠肝脏毒性、凋亡和氧化应激。
