亚砷酸钠对大鼠肝线粒体和微粒体酶的影响

研究了亚砷酸钠在体内、体外对大鼠肝线粒体丙酮酸脱氢酶（ＰＤＨ）、琥珀酸脱氢酶（ＳＤＨ）和微粒体酶细胞色素Ｐ－４５０、ｂ５、ＮＡＤ（Ｐ）Ｈ－细胞色素Ｃ还原酶、谷胱甘肽硫转移酶（ＧＳＴ）的影响；并通过观测亚砷酸钠与亚硒酸钠的作用及其对肝谷胱甘肽过氧化物酶、谷胱甘肽含量和线粒体脂质过氧化的影响，探讨亚砷酸钠的作用机理。结果表明：连续７天腹腔注射２０ｍｇ／ｋｇ的亚砷酸钠，线粒体ＰＤＨ、ＳＤＨ被抑制，分别相当于对照组的５１％和５８％。而亚硒酸钠可有效拮抗砷对ＰＤＨ、ＳＤＨ的抑制作用。亚砷酸钠显著降低肝ＧＳＨ的含量，并增强线粒体膜脂质过氧化作用（Ｐ＜０．０５）。在体内试验中，亚砷酸钠对谷胱甘肽过氧化物酶和肝微粒体酶无明显影响。亚砷酸钠在体外实验中，浓度在１０－７～１０－３ｍｏｌ／Ｌ的范围内，抑制ＳＤＨ的活力，提高ＧＳＨ的含量，且呈剂量－效应关系。结果提示，亚砷酸钠对机体的作用与其对ＬＰＯ和体内巯基的影响有关

Effects of arsenite on rat hepatic mitochondrial and microsomal enzymes

The effects of arsenite on the activities of several liver enzymes including mitochondrial pyruvate dehydrogenase (PDH) and succinate dehydrogenase(SDH), microsomal cytochrome P 450 and b5, NAD(P)H cytochrome C reductase and glutathione S transferase, were studied. Also, the effects of arsenite on the mitochondrial membrane lipid peroxidation(LPO), the content of hepatic cytosol reduced glutathione and the activity of glutathione peroxidase were investigated in rats. The results indicated: the activities of mitochondrial PDH and SDH were 51% and 58% of the control activities respectively after arsenite was administered by intraperitoneal injection(i.p.) daily for 7 consecutive days at a dose of 20mg/kg. However, sodium selenite played a significant antagonistic role with arsenite on the activities of mitochondrial PDH and SDH. Administration of arsenite led to a potential decrease of GSH content. The increase in lipid peroxidation of liver mitochondrial membrane prepared from rats treated with arsenite was also observed (P<0.05 ). Arsenite did not affect the liver cytosolic glutathione peroxidase and microsomal enzyme activities in vivo. In vitro test, liver mitochondria and cytosol treated with arsenite(final concentration was 10 -7 ～10 -3 mol/L) led to a decreased levels of SDH activity and GSH content and an increased levels of mitochondrial LPO with a dose dependence manner which is similar to the results attained by experiments in vivo. The results suggested that the toxic effects of arsenite on rat were associated with the levels of LPO and SH group.