Department of Biology, Pamukkale University, Kinikli Campus, 20070 Denizli, Turkey.
Biomed Res Int. 2013;2013:358945. doi: 10.1155/2013/358945. Epub 2013 Jul 18.
The present study was designed to evaluate different doses of ellagic acid (EA) in vivo in rats for its potential to modulate hepatic phases I, II, and antioxidant enzymes. EA (10 or 30 mg/kg/day, intragastrically) was administered for 14 consecutive days, and activity, protein, and mRNA levels were determined. Although the cytochrome P450 (CYP) 2B and CYP2E enzyme activities were decreased significantly, the activities of all other enzymes were unchanged with the 10 mg/kg/day EA. In addition, western-blot and qRT-PCR results clearly corroborated the above enzyme expressions. On the other hand, while the NAD(P)H:quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activities were increased significantly, CYP1A, 2B, 2C, 2E, and 19 enzyme activities were reduced significantly with 30 mg/kg/day EA. In addition, CYP2B, 2C6, 2E1, and 19 protein and mRNA levels were substantially decreased by the 30 mg/kg/day dose of EA, but the CYP1A protein, and mRNA levels were not changed. CYP3A enzyme activity, protein and mRNA levels were not altered by neither 10 nor 30 mg/kg/day ellagic acid. These results indicate that EA exerts a dose-dependent impact on the metabolism of chemical carcinogens and drugs by affecting the enzymes involved in xenobiotics activation/detoxification and antioxidant pathways.
本研究旨在评估不同剂量的鞣花酸（EA）在体内对大鼠肝相 I、II 期和抗氧化酶的潜在调节作用。EA（10 或 30mg/kg/天，灌胃）连续给药 14 天，测定其活性、蛋白和 mRNA 水平。虽然细胞色素 P450（CYP）2B 和 CYP2E 酶活性显著降低，但 10mg/kg/天 EA 组的所有其他酶活性均无变化。此外，western-blot 和 qRT-PCR 结果清楚地证实了上述酶的表达。另一方面，虽然 NAD(P)H：醌氧化还原酶 1（NQO1）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPX）和谷胱甘肽 S-转移酶（GST）活性显著增加，但 30mg/kg/天 EA 使 CYP1A、2B、2C、2E 和 19 酶活性显著降低。此外，30mg/kg/天 EA 使 CYP2B、2C6、2E1 和 19 的蛋白和 mRNA 水平显著降低，但 CYP1A 蛋白和 mRNA 水平未发生变化。CYP3A 酶活性、蛋白和 mRNA 水平不受 10 或 30mg/kg/天 EA 的影响。这些结果表明，EA 通过影响参与外源化学物激活/解毒和抗氧化途径的酶，对化学致癌物和药物的代谢产生剂量依赖性影响。
