硒缺乏和酶诱导剂对大鼠肝硒和非硒谷胱甘肽过氧化物酶的影响

谷胱甘肽过氧化物酶(GSHPx)是体内一种重要的抗氧化剂酶,此酶有含硒和不含硒两种。含硒GSHPx可以过氧化氢和有机氢过氧化物为底物,而非硒GSHPx仅以有机氢过氧化物为底物。本文报告以过氧化羟基异丙苯(CHP)作底物,测定大鼠肝总GSHPx活性的条件及硒缺乏和酶诱导剂对硒和非硒GSHPx活性的影响。     

硒对老龄雄性大鼠全血、心、肝、肾谷胱甘肽过氧化物酶的活性及LPO含量的影响

采用老龄(20～21月龄)雄性 VVi—star 大鼠,观察给予老龄雄性大鼠机体补充 Se后对全血、心、肝、肾的硒谷胱甘肽过氧化物酶(SeGSH—Px)活性和脂质过氧化物(LPO)含量的影响。结果表明、机体补充硒后可使老龄大鼠全血和上述脏器组织 SeGSH—Px 活性升高,LPO 含量降低,从而起到延缓衰老的作用。     

云芝多糖对小鼠心、肝、脾、肾和红细胞抗氧化能力的影响

通过测定小鼠心、肝、脾、肾组织和红细胞脂质过氧化物含量和硒谷胱甘肽过氧化物酶活性，观察了云芝多糖对机体各组织及红细胞抗氧化能力的影响。结果表明，云芝多糖能提高机体各组织的硒谷胱甘肽过氧化物酶活性及降低脂质过氧化物含量，提示云芝多糖能有效地提高机体抗氧化能力，为防止或减轻脂质过氧化损伤提供了实验依据。     

云硒冲剂(SeY)对小鼠GSH-Px活力和LPO含量影响的研究

目的：研究云硒冲剂（SeY)对正常鼠及CCl4损伤肝鼠的肝脏保护及抗氧化作用。方法：以常用的硒制剂Na2SeO3为对照来研究云硒冲剂（SeY)对正常鼠及CCl4损伤肝鼠血、肝GSH－Px活力和正常鼠血LPO含量影响,以DTNB直接法测定GSH－Px活力,硫代巴比妥酸荧光法测定LPO分量。结果：云硒冲剂能显著提高正常鼠血、肝GSH－Px活力（P＜0．001）,及CCl4损伤肝鼠肝GSH－Px活力,并可显著降低正常鼠血LPO含量。结论：云硒冲剂（SeY)具有一定的抗氧化和抗肝损伤的作用。     

四氯化碳体外与大鼠肝微粒体膜作用的研究

向大鼠肝微粒体膜悬液中加入CCl_4(0.05～1μl/ml),可致膜脂过氧化和膜脂流动性降低。二巯基苏糖醇(DTT)和普鲁卡因能拮抗上述效应。CCl_4与微粒体膜作用后,ANS荧光强度降低并出现红移。结果提示,CCl_4诱发的膜脂过氧化可致微粒体膜的物理状态发生改变。     

氟乐灵对大鼠肝和肾微粒体酶的影响

氟乐灵对大鼠肝和肾微粒体酶的影响杜柳涛邬惠琼柴莲花（同济医科大学环境毒理学研究室，武汉４３００３０）氟乐灵是一种高效低毒的除草剂，化学名为４－三氟甲基－２，６－二硝基－Ｎ，Ｎ－二正丁基苯胺，主要用于防治大多数禾本科杂草和许多一年生阔叶杂草，在许多国家...     

亚硝基谷胱甘肽对大鼠肝微粒体谷胱甘肽转移酶的激活及机制

目的　探索一氧化氮供体亚硝基谷胱甘肽(GSNO)能否在体外通过S 亚硝酰化机制激活大鼠肝微粒体谷胱甘肽转移酶 (mGST)。方法　微粒体粗提物与GSNO体外共孵育 ,测定mGST催化动力学改变 ,结合N 乙基马来酰亚胺 (NEM )再激活实验和二巯基苏醇 (DTT)逆转实验 ,以及酶蛋白游离巯基和酶S 亚硝酰化蛋白的改变 ,研究酶的激活机制。结果　GSNO在 0 .12 5～ 2mmol·L- 1浓度范围内呈浓度和时间 (3～ 15min)依赖性地激活mGST ,NEM对酶的再激活效应消失 ,DTT可以逆转上述激活作用 ,同时酶蛋白游离巯基浓度依赖性减少 ,而S 亚硝酰化蛋白浓度依赖性增多。结论　GSNO体外可激活大鼠肝mGST ,激活机制可能与mGST第 4 9位半胱氨酸 (Cys4 9)的巯基被亚硝酰化形成S 亚硝基硫醇结构有关。     

草甘膦对大鼠肝微粒体酶活力的影响及其机理初探

运用体内试验和体外试验的方法，研究了草甘膦对大鼠肝微粒体酶活力的影响，并对其作用机理进行了初步探讨。结果表明，体内试验中，草甘膦能明显增加细胞色素Ｐ４５０含量，诱导氨基比林Ｎ－脱甲基酶（ＡＰＮＤ）和乙基吗啡Ｎ－脱甲基酶（ＥＭＮＤ）的活力；体外试验中，在３．３×１０－８～３．３×１０－４ｍｏｌ／Ｌ浓度范围内，未见草甘膦对Ｐ４５０含量有明显增加，而在２×１０－６ｍｏｌ／Ｌ和２．５×１０－５～２×１０－４ｍｏｌ／Ｌ浓度范围内可分别对ＡＰＮＤ和ＥＭＮＤ呈现诱导作用，在２×１０－８～２×１０－４ｍｏｌ／Ｌ浓度范围内，随草甘膦浓度增高，ＡＰＮＤ和ＥＭＮＤ活力均有上升趋势。初步观察结果，草甘膦在体内对肝微粒体酶诱导作用机理与其促进蛋白质合成作用有关。     

Effects of cadmium treatment on selenium-dependent and selenium independent glutathione peroxidase activities and lipid peroxidation in the kidney and liver of rats maintained on various levels of dietary selenium

Rats fed a basal, low-selenium diet, or this diet supplemented with 0.1 ppm and 1.0 ppm selenium and treated with cadmium, showed significant reductions in the activity of the selenoenzyme glutathione peroxidase in kidney and liver. Cadmium treatment resulted in a significant increase in the activity of selenium-independent glutathione peroxidase activity in the liver of selenium-supplemented rats. Selenium-independent glutathion peroxidase activity was significantly reduced in the kidney of rats fed the basal low-selenium diet. There was no significant increase in lipid peroxidation in any of the groups studied. Cadmium concentrations in the kidney and liver of these animals ranged from about 250 to 700 g Cd/g tissue, dry weight.Supported by NIEHS Center Grant ES-00159 and a Grant from the Selenium-Tellurium Development Association     

外源性一氧化氮对大鼠肝脏抗氧化物酶和药物代谢酶活性的影响

用亚硝基铁氰化钠(SNP)作为NO生成前体,以 0, 1, 2, 4 和 8 mg·kg^-1 ip 给予大鼠,每日一次,连续 5 d,来研究外源性NO对大鼠肝脏细胞色素 P450, 苯胺羟化酶(AH), 谷胱甘肽S-转移酶(GST)等药物代谢酶和过氧化氢酶(Cat), 谷胱甘肽过氧化物酶(GSH-Px), 超氧化物歧化酶(SOD)等抗氧化物酶活性以及脂质过氧化的体内影响情况. 结果表明外源性NO能明显降低大鼠肝脏SOD, Cat, AH 的活性和细胞色素P450的含量(P<0.05),并且高剂量组还能明显促进脂质过氧化发生(P<0.05), 但对GSH-Px和GST的活性则无明显影响.     

外源性一氧化氮对大鼠肝脏抗氧化物酶和药物代谢酶活性的影响

用亚硝基铁氰化钠（ＳＮＰ）作为ＮＯ生成前体,以０,１,２,４和８ｍｇ·ｋｇ－１ｉｐ给予大鼠,每日一次,连续５ｄ,来研究外源性ＮＯ对大鼠肝脏细胞色素Ｐ４５０,苯胺羟化酶（ＡＨ）,谷胱甘肽Ｓ－转移酶（ＧＳＴ）等药物代谢酶和过氧化氢酶（Ｃａｔ）,谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）,超氧化物歧化酶（ＳＯＤ）等抗氧化物酶活性以及脂质过氧化的体内影响情况．结果表明外源性ＮＯ能明显降低大鼠肝脏ＳＯＤ,Ｃａｔ,ＡＨ的活性和细胞色素Ｐ４５０的含量（Ｐ＜０．０５）,并且高剂量组还能明显促进脂质过氧化发生（Ｐ＜０．０５）,但对ＧＳＨ－Ｐｘ和ＧＳＴ的活性则无明显影响     

Drug-induced lipid peroxidation in mice—I Modulation by monooxegenase activity,glutathione and selenium status

Feeding male mice for 2 days with sucrose leads to a decrease of total liver glutathione by more than 50 per cent when compared to controls. Such animals were intoxicated with 300 mg/kg paracetamol and upon administration of inducers of the drug-metabolizing system, in vivo and vitro lipid peroxidation in these animals was largely increased as well as the susceptibility to the drug. Pretreatment of the mice with methylcholanthrene led to a 28-fold, with benzo(α)pyrene to a 22-fold, and with phenobarbital to a tenfold increase in ethane exhalation. In vivo administration of various monooxygenase inhibitors showed that all agents effectively inhibit paracetamol-induced lipid peroxidation. It is concluded that phase I metabolism of paracetamol is a prerequisite for the manifestation of drug-induced lipid peroxidation.Selenium deficiency in mice neither affected hepatic levels of glutathione nor its decrease following sucrose feeding, nor glutathione transferase, superoxide dismutase, catalase and glutathione reductase activity. Selenium-dependent glutathione peroxidase activity of selenium-deficient mice, reactive with H₂O₂ as well as with t-butylhydroperoxide, decreased to 5 per cent of the supplemented controls. A glutathione peroxidase activity, which utilized cumenehydroperoxide as a substrate but insensitive to selenium deficiency, was found. Selenium-deficient diethylmaleate-pretreated animals were much more susceptible to paracetamol-induced lipid peroxidation than controls. Supplemented diethylmaleate-pretreated animals showed no signs of lipid peroxidation if treated with 100 mg/kg aminopyrine or ethylmorphine. However, deficient animals exhibited high ethane exhalation rates, drastically increased serum transaminases, loss of hepatic glutathione and mortality upon administration of these drugs. Qualitatively similar results with lower ethane exhalation rates were observed when 125 mg/kg furosemide was administered to diethylmaleate-pretreated selenium-deficient or -adequate mice. Even administration of 200 mg/kg ethoxycoumarin in combination with diethylmaleate lead to significant lipid peroxidation in phenobarbital-induced mice.The results demonstrate that in vivo selenium-dependent glutathione peroxidase plays a predominant role within the glutathione redox couple system. The enzyme protects the liver from peroxidative damage evoked by phase I metabolism of various drug types, as long as sufficient glutathione is available. It is suggested that activated oxygen released from the microsomal monooxygenase is the species responsible for the observed lipid peroxidation accompanied by severe acute liver lesions.     

Effects of dietary selenium supplementation on serum and liver selenium,serum malondialdehyde and liver glutathione peroxidase activity in rats consuming thermally oxidized sunflower oil

The present study compared the effects of four isocaloric diets containing (1) fresh sunflower oil not supplemented with selenium (Fresh), (2) oxidized sunflower oil not supplemented with selenium (Oxidized), (3) fresh sunflower oil supplemented with 1 ppm selenium as sodium selenite (Fresh + Se), (4) oxidized sunflower oil supplemented with 1 ppm selenium as sodium selenite (Oxidized + Se) on serum MDA concentrations, liver GPx activity and serum and liver selenium contents in growing male Sprague Dawley rats during a period of 43 days. The oxidized oil used was prepared by heating fresh sunflower oil at 180 °C for 48 h. Serum and liver selenium contents and liver GPx activity were significantly higher in the selenium supplemented groups compared to the non-selenium supplemented groups, but these parameters did not differ significantly between the oxidized oil fed groups and the fresh oil fed groups. Serum MDA concentrations increased significantly in the Oxidized group compared to the Fresh group. This suggests that the ingestion of oxidized oil resulted in, in vivo lipid peroxidation. Serum MDA concentrations remained significantly higher even in comparison of the Oxidized + Se group with the Oxidized group. Our results emphasize that the consumption of oxidized oil increases in vivo lipid peroxidation and thus can be deleterious to health. However, we did not observe a significant beneficial effect of selenium supplementation upon the ingestion of thermally oxidized oil on lipid peroxidation.     

Effect of dietary co-administration of sodium selenite on sodium arsenite-induced ovarian and uterine disorders in mature albino rats.

The subchronic treatment of mature female Wistar-strain albino rats in diestrous phase with sodium arsenite at a dose of 0.4 ppm/100 g body weight/rat/day via drinking water for period of 28 days (seven estrous cycles) caused a significant reduction in the plasma levels of leutinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol along with a significant decrease in ovarian activities of delta five, 3 beta-hydroxysteroid dehydrogenase (Delta5,3beta-HSD), and 17 beta-hydroxysteroid dehydrogenase (17beta-HSD) followed by a reduction in ovarian and uterine peroxidase activities. A significant weight loss of the ovary and uterus was also observed after this treatment, along with a prolonged diestrous phase and a high accumulation of arsenic in the plasma and these organs. Moreover, sodium arsenite was also responsible for ovarian follicular and uterine cell degeneration characterized by a high number of regressing follicles and a reduction in the uterine luminal diameter, respectively, in comparison with the controls. A dietary supplementation of sodium selenite at the dose of 0.6 mg/100 g body weight/rat/day for a period of 28 days along with arsenic treatment minimized the gonadal weight loss significantly and increased the activities of the ovarian steroidogenic enzymes as well as the ovarian and uterine peroxidase at the control level. Selenium was also able to increase the plasma levels of LH, FSH, and estradiol toward the control level. Vaginal smears showed normal estrous cyclicity in sodium selenite-supplemented arsenic-treated rats along with lower arsenic levels in the plasma and gonadal tissue in comparison with arsenic-only-treated rats. Histological sections of ovary and uterine tissues in the control and experimental groups confirmed that sodium selenite supplementation was able to prevent arsenic-induced histopathological changes in the ovary and uterus. Plasma levels of norepinephrine and dopamine in the midbrain and diencephalon decreased significantly, whereas the serotonin level was increased significantly after 28 days of sodium arsenite treatment. All of these parameters were, in most cases, unchanged from the control level when sodium selenite was co-administered with sodium arsenite. Arsenic intoxication was also associated with increased liver weight and elevation in the activities of hepatic and renal acid phosphatase, alkaline phosphatase, and transaminases, but selenium co-administration was not able to change these toxic effects of arsenic. The results of our experiments indicate the significant protective action of sodium selenite on arsenic-induced toxicity in the female reproductive system, while there was no significant protective effect of selenium on arsenic-induced toxicity in other organs.     

Genotoxicity of sodium arsenite and DNA fragmentation in ovarian cells of rat

Present study examined the genotoxic effects of arsenite in ovarian tissue of rat at 56 days of age. Immature (28 days old) female rats were exposed to different doses (50, 100, and 200 ppm) of sodium arsenite in drinking water for 28 days. DNA damage in ovarian tissue was measured by comet assay. All doses induced significant decrease in ovarian weight in a dose-dependent manner compared to control, more prominently at (P < 0.001) 100 and 200 ppm. All the comet assay parameters showed significant difference with arsenite treatment compared to control group. In treatment groups, mean number of cells with intact DNA decreased while, mean comet number increased (P < 0.001) in a dose-dependent manner compared to control. Significant decrease (P < 0.05) was observed in mean comet length, height, comet head diameter and %DNA in comet head of high dose groups compared to control group. Dose dependent increase was found in mean comet tail length, %DNA in tail, tail moment and olive tail moment in high dose groups compared to control group. The study indicates that arsenic caused DNA damage to ovarian cells particularly at high doses and ensure comet assay as an effective method to detect DNA damage in tissue caused by metals.     

Effects of methiocarb on lipid peroxidation and glutathione level in rat tissues

Methiocarb is an N-methylcarbamate insecticide used worldwide in agriculture and health programs. The aim of this study was to investigate the possible effects of methiocarb to induce lipid peroxidation (LPO) in tissues of male Wistar rats following single and repeated oral exposures. Animals were divided into six different groups, and methiocarb was administered by orally at doses 25, 10, and 2?mg/kg body weight for 1, 5, and 28 days, respectively. Liver, kidney, brain, and testis tissues were taken from the rats for the biochemical examinations. LPO and reduced glutathione (GSH) levels were determined in the tissues. LPO was significantly increased in liver, kidney, brain, and testis after 1-, 5-, and 28-day treatments of methiocarb. GSH levels were significantly increased in the 1-day period and significantly decreased in the 5- and 28-day periods in all tissues after methiocarb administration. It is concluded that methiocarb may induce LPO and produce disturbances on the GSH levels in liver, kidney, testis, and brain of rats. This suggests that methiocarb-induced toxicity may be associated with oxidative stress to cellular membranes. Further studies are required to better understand the role of oxidative stress on methiocarb-induced toxicity.     

红雪茶粗多糖对高脂性脂肪肝大鼠防治作用的研究

<正>红雪茶(Lethariella cladonioides)又名鹿心茶、金丝茶等,属梅花衣科金丝属地衣类,目前已发现红雪茶具有抗炎、抗疲劳及抗辐射等作用[1],并分离出了如雪茶素、瑞藏酸等化学成分[2]。本实验室首次从中提取出红雪茶粗多糖(LCP),通过高糖高脂饲料建立高脂性脂肪肝大鼠模型并同时灌服