Chadha Vijayta Dani, Vaiphei K, Dhawan D K
Department of Biophysics, Panjab University, Chandigarh 160014, India.
Mol Cell Biochem. 2007 Oct;304(1-2):101-8. doi: 10.1007/s11010-007-9490-x. Epub 2007 May 26.
The present study evaluated the inhibitory effects of zinc on colonic antioxidant defense system and histoarchitecture during 1,2 dimethylhydrazine (DMH) induced colon carcinogenesis in male Spraque Dawley rats. The rats were segregated into four groups viz., normal control, DMH treated, zinc treated, DMH + zinc treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 weeks. Zinc (in the form of zinc sulphate) was supplemented to rats at a dose level of 227 mg/l in drinking water, ad libitum for the entire duration of the study. Increased lipid peroxidation was accompanied by a decrease in reduced glutathione (GSH), glutathione reductase (GR), glutathione-s-transferase (GST), superoxide dismutase (SOD), and catalase. Administration of zinc to DMH treated rats significantly decreased the lipid peroxidation levels with simultaneous enhancement of GSH, GR, GST, SOD, and Catalase. Histopathological studies from DMH treated rats revealed disorganization of colonic histoarchitecture. However, zinc treatment to DMH treated rats greatly restored normalcy in the colonic histoarchitecture, with no apparent signs of abnormality. Energy Dispersive X-Ray Fluorescence (EDXRF) studies revealed a significant decrease in tissue concentrations of zinc in the colon following DMH treatment, which upon zinc supplementation were recovered to near normal levels. In conclusion, the results of this study suggest that zinc has a beneficial effect during the initiation of key events leading to the development of experimentally induced carcinogenesis.
本研究评估了锌对1,2 - 二甲基肼（DMH）诱导的雄性Sprague Dawley大鼠结肠癌发生过程中结肠抗氧化防御系统和组织结构的抑制作用。将大鼠分为四组，即正常对照组、DMH处理组、锌处理组、DMH + 锌处理组。通过每周皮下注射DMH（30 mg/kg体重），持续8周诱导结肠癌发生。在整个研究期间，以227 mg/l的剂量水平在饮用水中随意补充硫酸锌形式的锌给大鼠。脂质过氧化增加伴随着还原型谷胱甘肽（GSH）、谷胱甘肽还原酶（GR）、谷胱甘肽 - S - 转移酶（GST）、超氧化物歧化酶（SOD）和过氧化氢酶的减少。给DMH处理的大鼠施用锌显著降低了脂质过氧化水平，同时增强了GSH、GR、GST、SOD和过氧化氢酶。DMH处理大鼠的组织病理学研究显示结肠组织结构紊乱。然而，对DMH处理的大鼠进行锌处理极大地恢复了结肠组织结构的正常状态，没有明显的异常迹象。能量色散X射线荧光（EDXRF）研究显示，DMH处理后结肠组织中锌的浓度显著降低，补充锌后恢复到接近正常水平。总之，本研究结果表明，在导致实验性诱导致癌作用发生的关键事件起始阶段，锌具有有益作用。
