Sidhu Pardeep, Garg M L, Dhawan D K
Department of Biophysics, Panjab University, Chandigarh 160014, India.
Chem Biol Interact. 2004 Nov 20;150(2):199-209. doi: 10.1016/j.cbi.2004.09.012.
This study was planned to determine the protective role of zinc, if any, in attenuating the toxicity induced by nickel sulfate in rat liver. Female Sprague Dawley (SD) rats received either nickel alone in the dose of 800 mg/l in drinking water, zinc alone in the dose of 227 mg/l in drinking water, and nickel plus zinc or drinking water alone for a total duration of eight weeks. The effects of different treatments were studied on various parameters in rat liver which include antioxidant enzymes, levels of nickel and zinc and histoarchitecture at the light microscopic level. Further, the activities of hepatic marker enzymes AST and ALT were also studied in rat serum. Nickel treatment to the normal control animals, resulted in a significant increase in lipid peroxidation and enzyme activities of catalase and glutathione-S-transferase. On the contrary, nickel treatment to normal rats caused a significant inhibition in the levels of reduced glutathione. Superoxide dismutase activity was found to be decreased which however was not significant. Interestingly, when Zn was supplemented to nickel treated rats, the activities of catalase, and glutathione-S-transferase and the levels of GSH and lipid peroxidation came back to within normal limits. Activities of serum AST and ALT were increased significantly following nickel treatment to normal rats. Simultaneous zinc administration to nickel treated rats tended to restore the altered levels of AST and ALT. Normal control and zinc treated animals revealed normal histology of liver. On the other hand, nickel treated animals showed alterations in normal hepatic histoarchitecture which comprise of vacuolization of the hepatocytes and dilatation of sinusoids as well as increase in the number of bi-nucleated cells. Administration of zinc to nickel treated rats resulted in marked improvement in the structure of hepatocytes, thus emphasizing the protective potential of zinc in restoring the altered hepatic histoarchitecture. The nickel administration to normal rats indicated increased concentrations of nickel and decreased concentrations of zinc. However, zinc effectively brought the altered levels of nickel and zinc to within normal range. The study concludes that zinc has the potential in alleviating the toxic effects of nickel in rat liver because of its property to induce metallothionein (S-rich protein) as a free radical scavenger, or its indirect action in reducing the levels of oxygen reactive species.
本研究旨在确定锌在减轻硫酸镍对大鼠肝脏所致毒性方面是否具有保护作用。雌性斯普拉格-道利（SD）大鼠分别接受以下处理：饮用水中单独含800 mg/l镍、饮用水中单独含227 mg/l锌、镍加锌，或仅饮用普通水，为期8周。研究了不同处理对大鼠肝脏各种参数的影响，这些参数包括抗氧化酶、镍和锌的水平以及光镜下的组织架构。此外，还研究了大鼠血清中肝脏标志物酶AST和ALT的活性。对正常对照动物给予镍处理后，脂质过氧化以及过氧化氢酶和谷胱甘肽-S-转移酶的酶活性显著增加。相反，对正常大鼠给予镍处理导致还原型谷胱甘肽水平显著降低。超氧化物歧化酶活性降低，但不显著。有趣的是，当给经镍处理的大鼠补充锌时，过氧化氢酶和谷胱甘肽-S-转移酶的活性以及谷胱甘肽和脂质过氧化水平恢复到正常范围内。对正常大鼠给予镍处理后，血清AST和ALT活性显著增加。对经镍处理的大鼠同时给予锌倾向于使AST和ALT的改变水平恢复正常。正常对照和经锌处理的动物肝脏组织学正常。另一方面，经镍处理的动物肝脏正常组织架构出现改变，包括肝细胞空泡化、窦状隙扩张以及双核细胞数量增加。给经镍处理的大鼠给予锌导致肝细胞结构明显改善，从而强调了锌在恢复改变的肝脏组织架构方面的保护潜力。对正常大鼠给予镍表明镍浓度增加而锌浓度降低。然而，锌有效地使镍和锌的改变水平恢复到正常范围。该研究得出结论，锌具有减轻镍对大鼠肝脏毒性作用的潜力，这是因为其具有诱导金属硫蛋白（富含硫的蛋白质）作为自由基清除剂的特性，或者其在降低活性氧水平方面的间接作用。
