Okazaki Yasumasa, Iqbal Mohammad, Okada Shigeru
Department of Pathological Research, Faculty of Medicine, Okayama University Graduate School of Medicine and Dentistry, Japan.
Biochim Biophys Acta. 2005 Jun 10;1740(3):357-66. doi: 10.1016/j.bbadis.2004.09.006. Epub 2004 Sep 25.
Curcumin, a natural, biologically active compound extracted from rhizomes of Curcuma species, has been shown to act as a biological response modifier in various disorders. We have reported previously that the dietary supplementation of curcumin enhances the activities of antioxidant and phase II metabolizing enzymes in mice (M. Iqbal, S.D. Sharma, Y. Okazaki, M. Fujisawa, S. Okada, Dietary supplementation of curcumin enhances antioxidant and phase II metabolizing enzymes in ddY mice: possible role in protection against chemical carcinogenesis and toxicity, Pharmacol and Toxicol. 92 (2003) 33_38.) and inhibits ferric nitrilotriacetate (Fe-NTA) induced oxidative injury of lipids and DNA in vitro (M. Iqbal, Y. Okazaki, S. Okada, In vitro curcumin modulates Ferric Nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H(2)O(2))-induced peroxidation of microsomal membrane lipids and DNA damage, Teratogenesis Carcinogenesis and Mutagenesis Supplement 23 (2003) 151-160.). In our present study, Fe-NTA, a known complete renal carcinogen, which generate ROS in vivo, was given intraperitoneally to mice and curcumin was tested for its ability to inhibits oxidative stress and the activity of ornithine decarboxylase (ODC) as well as histopathological changes in the kidney. Substantial changes in glutathione, antioxidant enzymes as well as changes in phase II metabolizing enzymes were observed in the kidney at 12 h after treatment with Fe-NTA (9.0 mg Fe/kg body weight). Effect of oxidative stress induced by Fe-NTA were also demonstrated by the increase in lipid peroxidation as monitored by formation of thiobarbituric acid-reactive substances and 4-hydroxy-2-nonenal (HNE)-modified proteins in kidney. Likewise, the level of protein carbonyl contents, an indicator of protein oxidation was also increased after Fe-NTA administration. However, the changes in these parameters were restored to normal in curcumin-pretreated mice. The ODC activity in the kidney was significantly increased by Fe-NTA, while the increased ODC activity induced by Fe-NTA was normalized in curcumin-pretreated mice. In addition, curcumin pretreatment almost completely prevented kidney biomolecules from oxidative damage and protected the tissue against observed histopathological alterations.
姜黄素是从姜黄属植物根茎中提取的一种天然生物活性化合物，已被证明在多种疾病中可作为生物反应调节剂。我们之前报道过，在小鼠饮食中补充姜黄素可增强抗氧化酶和Ⅱ相代谢酶的活性（M. 伊克巴尔、S.D. 夏尔马、Y. 冈崎、M. 藤泽、S. 冈田，《饮食中补充姜黄素可增强ddY小鼠的抗氧化酶和Ⅱ相代谢酶：对预防化学致癌和毒性的可能作用》，《药理学与毒理学》，92卷（2003年），第33 - 38页），并且在体外可抑制次氮基三乙酸铁（Fe-NTA）诱导的脂质和DNA氧化损伤（M. 伊克巴尔、Y. 冈崎、S. 冈田，《体外实验中姜黄素调节次氮基三乙酸铁（Fe-NTA）和过氧化氢（H₂O₂）诱导的微粒体膜脂质过氧化和DNA损伤》，《致畸、致癌和诱变补充材料》，23卷（2003年），第151 - 160页）。在我们目前的研究中，给小鼠腹腔注射已知的完全性肾致癌物Fe-NTA（其在体内产生活性氧），并测试姜黄素抑制氧化应激、鸟氨酸脱羧酶（ODC）活性以及肾脏组织病理学变化的能力。在用Fe-NTA（9.0毫克铁/千克体重）处理12小时后，观察到肾脏中谷胱甘肽、抗氧化酶以及Ⅱ相代谢酶有显著变化。通过测定硫代巴比妥酸反应性物质的形成以及肾脏中4-羟基-2-壬烯醛（HNE）修饰蛋白来监测脂质过氧化增加，这也证明了Fe-NTA诱导的氧化应激作用。同样，蛋白质羰基含量（蛋白质氧化的一个指标）在给予Fe-NTA后也有所增加。然而，在预先用姜黄素处理的小鼠中，这些参数的变化恢复到了正常水平。Fe-NTA使肾脏中的ODC活性显著增加，而在预先用姜黄素处理的小鼠中，Fe-NTA诱导的ODC活性增加恢复到了正常水平。此外，姜黄素预处理几乎完全防止了肾脏生物分子的氧化损伤，并保护组织免受观察到的组织病理学改变。
