云芝多糖对小鼠肝脏超氧化物歧化酶活力和脂质过氧化的影响

云芝多糖对小鼠肝脏超氧化物歧化酶活力和脂质过氧化的影响魏文树１谭建权陈海生２（第二军医大学药理学教研室，上海２００４３３）云芝多糖（Ｃｏｒｉｏｌｕｓｖｅｒｓｉｃｏｌｏｒｐｏｌｙｓａｃｃｈａｒｉｄｅｓ，ＣＶＰ）系从长白山野生云芝中提取，含６７．５３％β...     

Effects of cadmium on glutathione peroxidase, superoxide dismutase, and lipid peroxidation in the rat heart: a possible mechanism of cadmium cardiotoxicity

Cadmium treatment of rats maintained on a low-selenium diet produced a significant increase in specific heart weight together with histopathological changes. This increase was accompanied by a decrease in the activities of the selenoenzyme, glutathione peroxidase, and the copper-containing enzyme superoxide dismutase, together with a rise in thiobarbiturate-reactive substances in the heart. Increased dietary selenium prevented the lowering of glutathione peroxidase activity but did not influence the effect of cadmium on superoxide dismutase. The effect of cadmium on thiobarbiturate-reactive materials was markedly reduced in the rats fed high dietary selenium.     

Effects of cadmium on lipid peroxides and superoxide dismutase in hepatic, renal and testicular tissue of rats

Daily i.p. administration of 0.5 mg cadmium (Cd)/kg body weight to rats for 3 mo enhanced lipid peroxidation and inhibited superoxide dismutase (SOD) activity in liver, kidney and testes. Accumulation of Cd and SOD inhibition was maximum in liver followed by kidney and testes, indicating a direct effect of Cd on SOD activity. This suggests a role of free radicals in causing cellular damage with long-term exposure to cadmium.     

石杉碱甲对老年大鼠异常的脂质过氧化和超氧化物歧化酶的改善作用(英文)

目的:研究石杉碱甲对老年大鼠海马、皮层和血清的脂质过氧化和超氧化物歧化酶的作用。方法:硫代巴比妥酸法测定组织中MDA水平;黄嘌呤氧化酶法测定组织中超氧化物歧化酶的活性。结果:雄性老年大鼠海马、皮层和血清中MDA水平和Mn-SOD活性明显高于成年大鼠。石杉碱甲明显降低雄性老年大鼠海马、皮层和血清中MDA水平和SOD活性,而对成年大鼠的这两项指标无明显影响。结论:石杉碱甲能明显改善衰老导致的自由基系统的异常变化,这种神经保护作用可能有益于AD的治疗。     

石杉碱甲对老年大鼠异常的脂质过氧化和超氧化物歧经酶的改善作用

AIM: To study the effects of huperzine A on lipid peroxidation and superoxide dismutase (SOD) in hippocampus, cerebral cortex, and serum of aged rats. METHODS: The level of lipid peroxidation was determined by thiobarbituric acid reactive substance method and represented as the concentration of malondialdehyde (MDA) in wet tissue. The activity of SOD was determined by xanthine-xanthine oxidase method and represented as the nitrite unit per gram protein in wet tissue. RESULTS: The levels of MDA and the manganese-SOD (Mn-SOD) activities in hippocampus, cerebral cortex, and serum of aged male rats were 2.3-2.8 times and 1.8-2.8 times, respectively, higher than those of adult male rats. Huperzine A (0.05 mg/kg, ig) lowered markedly the levels of MDA and the activities of Mn-SOD in aged male rats following 7-14 d consecutive administrations. The MDA levels in hippocampus, cerebral cortex, and serum decreased 44.7-52.8% (7 d) and 52.6-54.7% (14 d). The Mn-SOD activities in hippocampus, cerebral cortex, and serum lowered 25.0 -57.6% (7 d) and 56.0-74.2% (14 d). In adult rats, no marked change was found after 7-14 d consecutive administrations of huperzine A at a dose of 0.05 mg/kg. CONCLUSION: Huperzine A improved the abnormal free radicals in aged rats.     

老年小鼠肝脏组织胶原与SOD、LPO之间的关系

衰老是一个复杂的生理过程,为了探讨肝脏组织胶原与 SOD、LPO 之间的关系,说明老化过程中胶原随龄变化的机理,本实验采用健康昆明小鼠,观察肝脏组织胶原及 SOD、LPO 的随龄变化。结果表明老年小鼠肝脏组织胶原明显降低,且与 SOD 呈正相关(P<0.05),与 LPO 呈负相关(P<0.01),提示胶原的变化与 SOD、LPO 有着极其密切的联系。     

Antioxidant enzymes activity and lipid peroxidation in liver and kidney of rats exposed to cadmium and ethanol.

The oxidative status of liver and kidney of rats co-exposed to cadmium (50 mg Cd/l in drinking water) and ethanol (5 g EtOH/kg body weight/24 h, intragastrically) for 12 weeks was studied. The activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) as well as the concentration of malondialdehyde (MDA), as an indicator of lipid peroxidation, were measured in homogenates of the liver and kidney. Concentrations of zinc (Zn), copper (Cu), iron (Fe) and Cd in the serum or blood, and their content in the liver and kidney as well as EtOH concentration in the whole blood were assayed. Daily Cd intake in the Cd and Cd+EtOH groups was similar and ranged from 2.39 to 4.88 mg/kg body weight/24 h and from 2.64 to 4.14 mg/kg body weight/24 h, respectively. After the administration of EtOH alone, the activity of SOD increased in the kidney and decreased in the liver, whereas the activity of CAT decreased in both these organs, and MDA concentration increased in the liver and was unchanged in the kidney. The exposure to 50 mg Cd/l led to a decrease in the activities of SOD in the liver and CAT in the liver and kidney, and an increase in the kidney activity of SOD and MDA concentration in both these organs. In the rats co-exposed to Cd and EtOH, the kidney activity of SOD and the liver concentration of MDA were lower, whereas the kidney activity of CAT was higher compared to the Cd group. The concentration of Fe in the serum and its content in the liver of rats treated with EtOH increased, whereas the concentrations of Zn and Cu in the serum and the content of Zn, Cu and Fe in the kidney and that of Zn and Cu in the liver were unchanged. In the liver and kidney of rats treated with Cd alone, the content of Fe was decreased and that of Zn and Cu was enhanced. After EtOH administration to Cd-exposed rats, a decrease in Cu serum concentration and its liver content and an increase in Fe concentration in the serum and its content in the liver and kidney, compared to the group exposed to Cd alone, were noted. Moreover, EtOH decreased the blood Cd concentration and its accumulation in the liver and kidney of these animals. EtOH alone decreased Cd content in the liver and increased in the kidney, however the whole content of Cd in these organs was unchanged compared with control. The results of this study indicate that despite the ability of Cd and EtOH to induce the oxidative stress the effect in the liver and kidney is not intensified at simultaneous exposure to both substances. The changes in the studied indicators of oxidative stress (SOD, CAT and MDA) observed in the kidney and especially in the liver of the rats co-exposed to Cd and EtOH may result from an independent effect of Cd and/or EtOH and also from their interaction. The interactive effect may involve, among others, changes in Cd accumulation and content of Zn, Cu and Fe in these organs and their concentration in serum. Since the rats treated with Cd and Cd+EtOH had reduced drinking fluids intake that might result in dehydratation, the effect of the both xenobiotics on the oxidative status of the body may be not solely due to Cd and/or EtOH, but also the modyfing influence of accompanying alterations such as reduced water intake and dehydratation. The results of the study allow us to hypothesize that Cd-exposed alcohol misusers are not at enhanced risk of liver and kidney damage due to lipid peroxidation.     

姜黄素对鼠体内SOD活性和MDA含量的影响

目的：观察姜黄素对成年小鼠及老年大鼠体内超氧化物歧化酶（ＳＯＤ）和丙二醛（ＭＤＡ）含量的影响。方法：选用成年ＮＩＨ小鼠，每日腹腔注射姜黄素共７ｄ，观察血浆、脑及肝脏组织的ＳＯＤ活性及ＭＤＡ含量。选用雄性ＳＤ老年大鼠（＞２８月龄），用０．０２％姜黄素水溶液作为饮水，连续给药９ｗｋ，动态观察给药前及给药后９ｗｋ内血浆中ＳＯＤ和ＭＤＡ的含量。结果：姜黄素给药小鼠血浆及脑组织的ＭＤＡ含量下降，血浆、脑及肝脏组织的ＳＯＤ活性均明显提高，呈现一定的剂量依赖关系。老年大鼠给药后血浆中的ＭＤＡ含量明显降低，血浆ＳＯＤ的活性在给药后３ｗｋ呈现一过性升高。结论：姜黄素有抑制成年小鼠和老年大鼠体内脂质过氧化过程的作用，该作用除了与其本身的抗自由基效应有关外，还与其提高机体的ＳＯＤ活性作用有一定关系。     

N-乙酰半胱氨酸对实验性肝硬化大鼠肝纤维化与脂质过氧化的影响

目的:探讨N-乙酰半胱氨酸(NAC)对肝硬化大鼠的作用及其影响肝纤维化与脂质过氧化损伤的机制。方法:雄性Wistar大鼠36只,随机分成正常组(7只)、模型组(14只)、NAC组(15只)。以10μL·kg~(-1)剂量二甲基亚硝胺(DMN)腹腔注射,每周连续3d,每日1次,共4 wk,诱导大鼠肝硬化模型。成模后,NAC组以NAC 0．1 g·kg~(-1)灌胃,每日1次,共4 wk;模型组给予等量生理盐水灌胃。HE染色与天狼猩红染色观察肝组织炎症与胶原沉积;水解法测定肝组织羟脯氨酸含量;生化法检查血清肝功能指标[丙氨酸转氧酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBil)、清蛋白(Alh)等],肝组织超氧化物歧化酶(SOD)活性与丙二醛(MDA)含量;Western印迹法检测肝组织α-平滑肌肌动蛋白(α- SMA)与热休克蛋白47(HSP47)表达。结果:治疗4 wk后,模型组大鼠死亡7只,NAC组死亡3只, NAC明显提高肝纤维化大鼠的生存率(P＜0．01)。与正常组相比,模型大鼠肝脏肝细胞变性、坏死明显,炎性细胞浸润,胶原沉积并形成假小叶;血清ALT、AST和TBil升高,AIb下降;肝组织羟脯氨酸与MDA含量升高,SOD活性下降(P＜0．01)。而NAC可显著减轻肝脏炎症、肝细胞坏死与肝组织胶原沉积,改善模型大鼠异常的肝功能指标,降低肝组织羟脯氧酸与MDA含量,提高SOD活性(P＜0．05,P＜0．01),抑制模型大鼠肝组织HSP47与α-SMA蛋白的表达(P＜0．01)。结论:N-乙酰半胱氨酸有良好的治疗肝硬化作用,其作用机制与促进肝纤维化逆转及抗肝脏脂质过氧化有关。     

Gentamicin-induced kidney damage and lipid peroxidation in rats

Although it has been reported that injections of gentamicin induces lipid peroxidation in rat renal cortex (Ramsammy et al. (1985) Biochem. Phannacol. 34, 3895–3900), our results showed no modification of thiobarbituric-reagent substances (TBARS) or in analysis of the polyunsaturated fatty acid profile. Moreover, endogenous vitamin E and glutathione were not consumed. In in vitro systems, gentamicin incubated with microsomes, homogenates and kidney slices from the normal rat failed to induce lipid peroxidation. We show that the increase in TBARS in vivo detected by Ramsammy et al. was wrongly attributed to the oxidant power of gentamicin. As this antibiotic does react positively to thiobarbituric acid in the presence of a system generating free radicals, it is possible that these authors accidentally introduced such a system into their experiments.     

Changes in lipid peroxidation and activities of xanthine oxidase, superoxide dismutase and catalase in kidneys of cephaloridine-administered rats

To elucidate the toxic and protective mechanisms responsible for cephaloridine (CER)-induced nephrotoxicity, changes in renal formation of malondialdehyde and renal activities of xanthine oxidase, superoxide dismutase and catalase were mainly investigated for 15 days in rats that received single intravenous injections of CER in doses of 100 and 1,000 mg/kg body weight. In the 100 mg/kg group, the above items determined remained within the control levels. In the 1,000 mg/kg group, renal formation of malondialdehyde was observed to be accelerated with the following two stages: highly in the early stage (the 3rd hour to the 2nd day, especially at the 3rd hour) and more highly in the late stage (the 2nd to the 7th day). Concerning the other items determined, significantly different changes were hardly observed in the 1,000 mg/kg group within the 12th hour of the early stage, while the rises in renal activities of xanthine oxidase and falls in renal activities of superoxide dismutase and catalase were observed in the late stage. These results suggested that the increment in malondialdehyde formation in the late stage might be explained enzymatically by both the rises in the activities of xanthine oxidase and the declines in the activities of superoxide dismutase and catalase and that those in the early stage did not relate directly to the above renal enzymatic systems.     

Effects of antioxidants on oxygen toxicity in vivo and lipid peroxidation in vitro.

Convulsions and pulmonary damage result when animals are exposed to hyperbaric oxygen at pressures above about 300 kPa. Several hydroxyl radical scavengers (namely dimethylsulphoxide, dimethylthiourea and mannitol), the iron chelator desferrioxamine and the lipid antioxidant butylated hydroxytoluene were tested for possible protection against such hyperbaric oxygen toxicity. Dimethylthiourea and dimethylsulphoxide prolonged the latency to the first convulsion, but, surprisingly, dimethylthiourea very significantly increased pulmonary damage at both pressures used (515 and 585 kPa). Desferrioxamine also slightly increased lung damage at 585 kPa. Other antioxidants did not alter neurotoxicity or pulmonary toxicity induced by hyperbaric oxygen at 515 or 585 kPa. The antioxidants were also tested for their ability to inhibit lipid peroxidation (TBARS formation) in vitro. Desferrioxamine (5 and 50 microM), and butylated hydroxytoluene (0.1 mM and 1 mM) greatly inhibited TBARS formation in brain and lung homogenates incubated at 37 degrees. None of the hydroxyl radical scavengers affected TBARS levels in homogenates. There was no correlation between in vitro inhibition of lipid peroxidation and in vivo protection against oxygen toxicity.     

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     

镉所致肾损害与脂质过氧化的实验

每天以２ｍｇ／ｋｇ氯化镉生理盐水溶液给大鼠腹腔注射１５天，结果显示：氯化镉可引起肾功能的改变和脂质过氧化指标ＭＤＡ的升高及ＳＯＤ的下降，说明镉可诱发肾脏的脂质过氧化。亚细胞组分分析表明镉诱导的脂质过氧化主要发生在线粒体及微粒体中。比较脂质过氧化与肾损害出现的时间，可见染镉动物肾皮质及亚细胞组分ＭＤＡ的升高及ＳＯＤ的下降的时间均晚于肾功能异常。可以认为肾脏脂质过氧化并非镉引起肾损害的直接原因     

Curcumin ameliorates aflatoxin-induced lipid peroxidation in liver, kidney and testis of mice--an in vitro study

The present investigation was an attempt to evaluate the possible ameliorative effect of curcumin on aflatoxin-induced lipid peroxidation in liver, kidney and testis of mice in vitro. Tissues were collected from healthy Swiss strain male albino mice Mus musculus weighing 30-35 g. The homogenates were treated with aflatoxin (2-10 mg/mL) with and without curcumin (25-200 mg/mL). The results revealed that addition of aflatoxin (2-10 mg/mL) to homogenates caused significant increase in lipid-peroxidation which was maximal at 6 mg/mL aflatoxin concentration. However, concurrent addition of aflatoxin (6 mg/mL) and curcumin ((25-200 mg/mL) caused concentration-dependent amelioration in aflatoxin-induced lipid peroxidation.     

Effects of lipid peroxidation on activities of drug-metabolizing enzymes in liver microsomes of rats

A relationship was found between the formation of lipid peroxides and the activities of drug-metabolizing enzymes in liver microsomes of rats. Induction of lipid peroxidation by incubation with ferrous ion led to a sharp decline in the ability of the microsomal enzyme system to demethylate ethylmorphine. Inhibition of lipid peroxidation by EDTA increased the enzyme activity about two-fold. Addition of EDTA (0.1 mM) to the incubation mixture produced marked changes in the Michaelis constants of drug-metabolizing enzymes and in inhibition constants of SKF 525-A for drug-metabolizing enzymes.     

Isolated perfused lung histamine release, lipid peroxidation, and tissue superoxide dismutase from rats exposed to normobaric hyperoxia

Female Sprague-Dawley inbred rats were exposed to either 1 atm of 100% O2 for 24 h, or 65% O2 for 5 days, with or without pretreatment with disulfiram, an inhibitor of lung CuZn-SOD. After O2 exposure, the rats were killed, the lungs removed, and isolated perfused lungs (IPLs) prepared. The IPLs were perfused with modified Krebs-Henseleit buffer, and perfusate histamine, malondialdehyde (MDA), and lung tissue CuZn-SOD activity examined. Disulfiram administration decreased the LT50 of O2-exposed rats from 65 to 36 h. Histamine and MDA in the perfusate from the IPL prepared from rats exposed to 100% O2 for 24 h were markedly increased. When rats were pretreated with disulfiram and exposed to 100% O2 for 24 h, histamine and MDA were increased an additional 77% and 45%, respectively. In separate experiments, 100% O2 exposure significantly decreased lung CuZn-SOD activity by 40% while IPL histamine and MDA were significantly increased. However, exposure of rats to 65% O2 for 5 days decreased lung CuZn-SOD by 69% but did not affect IPL histamine release or perfusate MDA. These studies suggest that IPL histamine release and/or MDA may be an early biochemical marker for pulmonary O2 toxicity, that lung CuZn-SOD activity may not be the only determinant in O2 toxicity, and other defense mechanisms may play a vital protective role during sublethal O2 exposures.     

Effects of phenolcarboxylic acids on superoxide anion and lipid peroxidation induced by superoxide anion.

The effects of phenolcarboxylic acids, caffeic acid, p-coumaric acid, and ferulic acid on the generation of superoxide anion and the production of lipid peroxide induced by superoxide anion were studied. Only ferulic acid anion among the phenolcarboxylic acids scavenged superoxide. Caffeic acid and ferulic acid inhibited lipid peroxidation induced by superoxide anion. These effects were comparable to those of superoxide dismutase or DL-alpha-tocopherol.     

Role of superoxide dismutase in in vivo and in vitro nitrate tolerance.

We assessed whether pharmacological inhibition of CuZn-superoxide dismutase (SOD) mimics the molecular mechanism of either in vitro or in vivo nitrovasodilator tolerance. In endothelium-intact aortic rings from in vivo tolerant rabbits the GTN- and acetylcholine (ACh)-induced maximal relaxation was attenuated by 36 and 23%, respectively. In vitro treatment of control rings with GTN (1 h 10 microM) similarly attenuated the vasorelaxant response to GTN, but not to ACh. Formation of superoxide radicals (*O2-) in endothelium-intact rings (lucigenin-chemiluminescence) increased 2.5 fold in in vivo tolerance, but significantly decreased in in vitro tolerance. The membrane associated NADH oxidase activity was increased 2.5 fold in homogenates of in vivo tolerant aortae, but was not changed in in vitro tolerant aorta. Conversely, SOD activity and protein expression was halved in in vivo tolerance, but SOD activity was not altered by in vitro tolerance. The *O2- scavenger tiron (10 mM) effectively restored the vasorelaxant response to GTN in in vivo tolerant aortic rings, but not the reduced response to GTN in in vitro tolerant rings. Pretreatment (1 h) of vessels with diethyldithiocarbamate (DETC; 10 mM) attenuated vasorelaxant responses to GTN and ACh, increased vascular *O2- production, and inhibited SOD activity in vessel homogenates to a similar degree as observed in in vivo tolerance. DETC-treatment of in vivo-tolerant vessels induced an additional increase in *O2- production. Increased *O2- production in in vivo nitrate tolerant aorta is associated with activation of vascular NADH oxidase and inactivation of CuZnSOD. Therefore, in vivo tolerance can be mimicked by in vitro inhibition of CuZnSOD, but not by in vitro exposure to GTN, which does not affect vascular *O2- production, NADH oxidase and CuZnSOD.     

内南五味子木脂素戈米辛J对肝线粒体膜脂质过氧化和超氧阴？…

目的　研究来自内南五味子的戈米辛J对脂质过氧化的影响和清除超氧阴离子自由基 (O·2 )的能力。方法　采用离体大鼠肝线粒体膜的脂质过氧化模型和黄嘌呤氧化酶 鲁米诺化学发光法。结果　戈米辛J象VitE一样能剂量依赖性抑制Fe2 VitC和ADP/NADPH所致的脂质过氧化 ;戈米辛J的IC50 分别为 5 75 ( 95 %可信限 :5 42～ 6 11)和0 95 ( 0 14～ 6 5 4) μmol·L-1。VitE的IC50 分别为 74 8( 30 2～ 185 3)和 6 5 1( 0 13～ 319) μmol·L-1。戈米辛J抑制Fe2 VitC和ADP/NADPH所致的脂质过氧化的作用比VitE的作用分别强 13倍和 6 8倍。戈米辛J也剂量依赖地抑制黄嘌呤 黄嘌呤氧化酶 鲁米诺化学发光 ,其抑制发光强度 5 0 %的浓度 (IC50 )为 2 18 2 2 μmol·L-1。结论　戈米辛J具有抑制OH·诱导的脂质过氧化和清除O·2 的作用