Iqbal M, Rezazadeh H, Ansar S, Athar M
Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.
Hum Exp Toxicol. 1998 Mar;17(3):163-71. doi: 10.1177/096032719801700307.
Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxic agent. In this communication, we show the modulatory effect of DL-alpha-tocopherol (Vitamin-E) on ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, toxicity and hyperproliferative response in rats. Fe-NTA-treatment enhances the susceptibility of renal microsomal membrane for iron-ascorbate-induced lipid peroxidation and hydrogen peroxide generation which are accompanied by a decrease in the activities of renal antioxidant enzymes, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and depletion in the level of renal glutathione. Parallel to these changes, a sharp increase in blood urea nitrogen and serum creatinine has been observed. In addition, Fe-NTA-treatment also enhances renal ornithine decarboxylase activity (ODC) and increases [3H]thymidine incorporation in renal DNA. Prophylactic treatment of animals with Vit.E daily for 1 week prior to the administration of Fe-NTA resulted in the diminution of Fe-NTA-mediated damage. Enhanced susceptibility of renal microsomal membrane for lipid peroxidation induced by iron-ascorbate and hydrogen peroxide generation were significantly reduced (P < 0.05). In addition, the depleted level of glutathione and inhibited activities of antioxidant enzymes recovered to significant levels (P < 0.05). Similarly, the enhanced blood urea nitrogen and serum creatinine levels which are indicative of renal injury showed a reduction of about 50% at a higher dose of Vit.E. The pretreatment of rats with Vit.E reduced the Fe-NTA-mediated induction in ODC activity and enhancement in [3H]thymidine incorporation in DNA. The protective effect of Vit.E was dose dependent. In summary, our data suggest that Vit.E is an effective chemopreventive agent in kidney and may suppress Fe-NTA-induced renal toxicity.
次氮基三乙酸铁（Fe-NTA）是一种强效肾毒性剂。在本报告中，我们展示了DL-α-生育酚（维生素E）对次氮基三乙酸铁（Fe-NTA）诱导的大鼠肾脏氧化应激、毒性和过度增殖反应的调节作用。Fe-NTA处理增强了肾微粒体膜对铁-抗坏血酸诱导的脂质过氧化和过氧化氢生成的敏感性，同时伴有肾脏抗氧化酶（过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶和谷胱甘肽-S-转移酶）活性降低以及肾脏谷胱甘肽水平耗竭。与这些变化同时发生的是，观察到血尿素氮和血清肌酐急剧增加。此外，Fe-NTA处理还增强了肾脏鸟氨酸脱羧酶活性（ODC），并增加了[3H]胸腺嘧啶核苷掺入肾脏DNA的量。在给予Fe-NTA之前，每天给动物预防性服用维生素E 1周，可减轻Fe-NTA介导的损伤。铁-抗坏血酸诱导的肾微粒体膜脂质过氧化增强敏感性和过氧化氢生成均显著降低（P < 0.05）。此外，耗竭的谷胱甘肽水平和受抑制的抗氧化酶活性恢复到显著水平（P < 0.05）。同样，表明肾脏损伤的血尿素氮和血清肌酐水平升高在较高剂量维生素E时降低了约50%。用维生素E预处理大鼠可降低Fe-NTA介导的ODC活性诱导和[3H]胸腺嘧啶核苷掺入DNA的增强。维生素E的保护作用呈剂量依赖性。总之，我们的数据表明维生素E是一种有效的肾脏化学预防剂，可能抑制Fe-NTA诱导的肾脏毒性。
