Guo Hongrui, Wu Bangyuan, Cui Hengmin, Peng Xi, Fang Jing, Zuo Zhicai, Deng Junliang, Wang Xun, Deng Jie, Yin Shuang, Li Jian, Tang Kun
Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Yaan, China.
Biol Trace Elem Res. 2014 Dec;162(1-3):288-95. doi: 10.1007/s12011-014-0132-3. Epub 2014 Sep 25.
The kidney serves as a major organ of nickel (Ni) excretion and is a target organ for acute Ni toxicity due to Ni accumulation. There are no studies on the Ni or Ni compound-regulated antioxidant enzyme mRNA expression in animals and human beings at present. This study was conducted to investigate the pathway of nickel chloride (NiCl2)-caused renal oxidative damage by the methods of biochemistry, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. Two hundred and eighty one-day-old broilers were randomly divided into four groups and fed on a control diet and three experimental diets supplemented with 300, 600, and 900 mg/kg of NiCl2 for 42 days. Dietary NiCl2 elevated the malondialdehyde (MDA), nitric oxide (NO), 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents, and reduced the ability to inhibit hydroxy radical in the NiCl2-treated groups. Also, the renal inducible nitric oxide synthase (iNOS) activity and mRNA expression levels were increased. The total antioxidant (T-AOC) and activities of antioxidant enzymes including copper zinc superoxide dismutase (CuZn-SOD), manganese superoxide dismutase (Mn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and glutathione-s-transferase (GST) were decreased, and the glutathione (GSH) contents as well were decreased in the kidney. Concurrently, the renal CuZn-SOD, Mn-SOD, CAT, GSH-Px, GST, and GR mRNA expression levels were decreased. The above-mentioned results showed that dietary NiCl2 in excess of 300 mg/kg caused renal oxidative damage by reducing mRNA expression levels and activities of antioxidant enzymes, and then enhancing free radicals generation, lipid peroxidation, and DNA oxidation.
肾脏是镍（Ni）排泄的主要器官，由于镍的蓄积，它也是急性镍中毒的靶器官。目前尚无关于镍或镍化合物对动物和人类抗氧化酶mRNA表达调控的研究。本研究采用生物化学、定量实时聚合酶链反应和酶联免疫吸附测定等方法，探讨氯化镍（NiCl2）所致肾脏氧化损伤的途径。将280只1日龄肉鸡随机分为4组，分别饲喂基础日粮和添加300、600和900 mg/kg NiCl2的三种试验日粮，为期42天。日粮中添加NiCl2使NiCl2处理组的丙二醛（MDA）、一氧化氮（NO）、8-羟基-2'-脱氧鸟苷（8-OHdG）含量升高，抑制羟自由基的能力降低。此外，肾脏诱导型一氧化氮合酶（iNOS）活性和mRNA表达水平增加。总抗氧化能力（T-AOC）以及包括铜锌超氧化物歧化酶（CuZn-SOD）、锰超氧化物歧化酶（Mn-SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）、谷胱甘肽还原酶（GR）和谷胱甘肽-S-转移酶（GST）在内的抗氧化酶活性降低，肾脏中的谷胱甘肽（GSH）含量也降低。同时，肾脏中CuZn-SOD、Mn-SOD、CAT、GSH-Px、GST和GR的mRNA表达水平降低。上述结果表明，日粮中NiCl2超过300 mg/kg可通过降低抗氧化酶的mRNA表达水平和活性，进而增强自由基生成、脂质过氧化和DNA氧化，导致肾脏氧化损伤。
