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.
Mol Cell Biochem. 2006 Oct;291(1-2):175-85. doi: 10.1007/s11010-006-9213-8. Epub 2006 Jun 10.
Ferric nitrilotriacetate (Fe-NTA) is a well-established renal carcinogen. Here, we have shown that Pluchea lanceolata (PL) belonging to the family Asteraceae. PL attenuates Fe-NTA induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. It promoted DEN (N-diethyl nitrosamine) initiated renal carcinogenesis by increasing the percentage incidence of tumors and induces early tumor markers viz. ornithine decarboxylase (ODC) and renal DNA synthesis. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) also enhances renal lipid peroxidation (LPO), xanthine oxidase (XO) and hydrogen peroxide (H(2)O(2)) generation with reduction in renal glutathione content (GSH), antioxidant enzymes, viz., glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), glucose-6-phosphate dehydrogenase and phase-II metabolizing enzymes such as glutathione-S-transferase and quinone reductase (QR). It also enhances blood urea nitrogen (BUN) and serum creatinine. Oral treatment of rats with PL extract (100 and 200 mg/kg body weight) resulted in significant decrease in lipid peroxidation (LPO), xanthine oxidase (XO), H(2)O(2) generation, blood urea nitrogen (BUN), serum creatinine, renal ODC activity, DNA synthesis (p < 0.001) and incidence of tumors. Renal glutathione content (p < 0.01), its metabolizing enzymes (p < 0.001) and antioxidant enzymes were also recovered to significant level (p < 0.001). Thus, present study supports PL as a potent chemopreventive agent and suppresses Fe-NTA-induced renal carcinogenesis and oxidative damage response in Wistar rat.
次氮基三乙酸铁（Fe-NTA）是一种公认的肾致癌物。在此，我们已经表明，属于菊科的单叶臭灵丹（PL）可减轻Fe-NTA诱导的大鼠肾脏氧化应激、过度增殖反应和肾脏致癌作用。它通过增加肿瘤发生率促进二乙基亚硝胺（DEN）引发的肾脏致癌作用，并诱导早期肿瘤标志物，即鸟氨酸脱羧酶（ODC）和肾脏DNA合成。Fe-NTA（9毫克铁/千克体重，腹腔注射）还会增强肾脏脂质过氧化（LPO）、黄嘌呤氧化酶（XO）和过氧化氢（H₂O₂）的生成，同时降低肾脏谷胱甘肽含量（GSH）、抗氧化酶，即谷胱甘肽过氧化物酶（GPx）、谷胱甘肽还原酶（GR）、过氧化氢酶（CAT）、葡萄糖-6-磷酸脱氢酶以及II相代谢酶，如谷胱甘肽-S-转移酶和醌还原酶（QR）。它还会提高血尿素氮（BUN）和血清肌酐水平。用PL提取物（100和200毫克/千克体重）对大鼠进行口服治疗，可使脂质过氧化（LPO）、黄嘌呤氧化酶（XO）、H₂O₂生成、血尿素氮（BUN）、血清肌酐、肾脏ODC活性、DNA合成（p < 0.001）以及肿瘤发生率显著降低。肾脏谷胱甘肽含量（p < 0. .01）、其代谢酶（p < 0.001）和抗氧化酶也恢复到显著水平（p < 0.001）。因此，本研究支持PL作为一种有效的化学预防剂，并抑制Wistar大鼠中Fe-NTA诱导的肾脏致癌作用和氧化损伤反应。
