Prasad Lakshmi, Khan Tajdar Husain, Jahangir Tamanna, Sultana Sarwat
Section of Chemoprevention and Nutrition Toxicology, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
Hum Exp Toxicol. 2006 Sep;25(9):523-9. doi: 10.1191/0960327106het652oa.
The present study is an effort to identify a potent chemopreventive agent against various diseases (including cancer) in which oxidative stress and cell proliferation plays an important causative role. This study was designed to investigate the effect of gallic acid against ferric nitrilotriacetic acid (Fe-NTA)-induced carcinogen/ drug metabolizing phase I and phase II enzymes, antioxidative parameters, kidney markers, tumour promotion markers and lipid peroxidation (LPO) in kidney of male Wistar rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) caused significant depletion in the detoxification and antioxidant enzyme armoury with concomitant elevation in renal LPO, serum creatinine, blood urea nitrogen, hydrogen peroxide generation, ornithine decarboxylase activity and [3H]thymidine incorporation into renal DNA. However, pretreatment of animals with gallic acid (10 and 20 mg/kg body weight) resulted in a significant decrease in the levels of the parameters measured (P <0.001). Renal glutathione content (P <0.001), glutathione metabolizing enzyme (P <0.001) and antioxidant enzyme levels were also recovered to a significant level (P <0.001). The enhanced reduced glutathione level and enzyme activities involved in xenobiotic metabolism and maintaining antioxidant status of cells are suggestive of a chemopreventive efficacy of gallic acid against Fe-NTA-mediated oxidative stress, toxicity and cell proliferative response in Wistar rats.
本研究旨在确定一种有效的化学预防剂,用于对抗各种疾病(包括癌症),其中氧化应激和细胞增殖起着重要的致病作用。本研究旨在调查没食子酸对三乙胺铁(Fe-NTA)诱导的雄性Wistar大鼠肾脏中致癌物质/药物代谢I相和II相酶、抗氧化参数、肾脏标志物、肿瘤促进标志物和脂质过氧化(LPO)的影响。Fe-NTA(9毫克铁/千克体重,腹腔注射)导致解毒和抗氧化酶储备显著减少,同时肾LPO、血清肌酐、血尿素氮、过氧化氢生成、鸟氨酸脱羧酶活性以及[3H]胸苷掺入肾DNA增加。然而,用没食子酸(10和20毫克/千克体重)预处理动物后,所测参数水平显著降低(P<0.001)。肾谷胱甘肽含量(P<0.001)、谷胱甘肽代谢酶(P<0.001)和抗氧化酶水平也显著恢复(P<0.001)。还原型谷胱甘肽水平的提高以及参与异生物质代谢和维持细胞抗氧化状态的酶活性表明,没食子酸对Wistar大鼠中Fe-NTA介导的氧化应激、毒性和细胞增殖反应具有化学预防功效。