Bando Inmaculada, Reus María Isabel Sánchez, Andrés David, Cascales María
Instituto de Bioquímica (CSIC-UCM), Facultad de Farmacia, Universidad Complutense, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain.
J Biochem Mol Toxicol. 2005;19(3):154-61. doi: 10.1002/jbt.20067.
Mercury is a highly toxic metal which induces oxidative stress. Superoxide dismutases, catalase, and glutathion peroxidase are proteins involved in the endogenous antioxidant defence system. In the present study rats were administered orally, by gavage, a single daily dose of HgCl2 for three consecutive days. In order to find a relation between the proteins involved in the antioxidant defence and mercury intoxication, parameters of liver injury, redox state of the cells, as well as intracellular protein levels and enzyme activities of Mn-dependent superoxide dismutase (MnSOD), Cu-Zn-dependent superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase (GPx) were assayed both in blood and in liver homogenates. HgCl2 at the doses of 0.1 mg/kg produced liver damage which that was detected by a slight increase in serum alanine aminotransferase and gamma glutamyl transferase. Hepatic GSH/GSSG ratio was assayed as a parameter of oxidative stress and a significant decrease was detected, as well as significant increases in enzyme activities and protein levels of hepatic antioxidant defence systems. Changes in both MnSOD and CuZnSOD were parallel to those of liver injury and oxidative stress, while the changes detected in catalase and GPx activities were progressively increased along with the mercury intoxication. Other enzyme activities related to the glutathione redox cycle, such as glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH), also increased progressively. We conclude that against low doses of mercury that produce a slight oxidative stress and liver injury, the response of the liver was to induce the synthesis and activity of the enzymes involved in the endogenous antioxidant system. The activities of all the enzymes assayed showed a rapidly induced coordinated response.
汞是一种剧毒金属，可引发氧化应激。超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶是参与内源性抗氧化防御系统的蛋白质。在本研究中，大鼠连续三天每天经口灌胃给予单次剂量的HgCl₂。为了找出参与抗氧化防御的蛋白质与汞中毒之间的关系，对血液和肝脏匀浆中的肝损伤参数、细胞氧化还原状态以及锰依赖性超氧化物歧化酶（MnSOD）、铜锌依赖性超氧化物歧化酶（CuZnSOD）、过氧化氢酶和谷胱甘肽过氧化物酶（GPx）的细胞内蛋白质水平和酶活性进行了测定。0.1mg/kg剂量的HgCl₂造成了肝损伤，血清丙氨酸氨基转移酶和γ-谷氨酰转移酶略有升高即可检测到。测定肝GSH/GSSG比值作为氧化应激参数，检测到显著下降，以及肝抗氧化防御系统的酶活性和蛋白质水平显著升高。MnSOD和CuZnSOD的变化与肝损伤和氧化应激的变化平行，而过氧化氢酶和GPx活性的变化则随着汞中毒程度逐渐增加。与谷胱甘肽氧化还原循环相关的其他酶活性，如谷胱甘肽还原酶（GR）和葡萄糖-6-磷酸脱氢酶（G6PDH）也逐渐增加。我们得出结论，对于产生轻微氧化应激和肝损伤的低剂量汞，肝脏的反应是诱导内源性抗氧化系统中相关酶的合成和活性。所有测定酶的活性均显示出快速诱导的协同反应。
