Free Radical Formation in Livers of Rats Treated Acutely and Chronically with Alcohol

The spin trapping method was used to assess formation of free radical intermediates in vivo before and after acute alcohol administration to rats. Ascorbyi radicals and spin adducts of dietary alcohol or endogenous compounds, such as lipids, were detected with higher frequency in bile from alcohol-fed rats than in corresponding samples from rats fed control diets. When alcohol was given acutely to these animals, the 1-hydroxyethyl radical metabolite of ethanol was also formed at higher rates in livers of rats that had been fed ethanol chronically. Furthermore, formation of lipid radicals was enhanced after acute alcohol administration. These data support the hypothesis that chronic alcohol administration causes development of oxi-dative conditions in the liver, which subsequently lead to formation of differing types of radicals. Liver microsomes from alcohol-fed rats also metabolized ethanol to the 1-hydroxyethyl radical at higher rates than controls.     

过氧化与胎儿宫内生长迟缓关系的研究

目的　探讨过氧化脂质 (LPO)及超氧化物歧化酶 (SOD)与胎儿宫内生长迟缓 (IUGR)的关系。方法　采用硫代巴比妥酸法及放射免疫法 ,测定 4 0例正常孕妇及 32例合并IUGR孕妇血和脐血中LPO及SOD水平。结果　与对照组相比 ,IUGR组孕妇血及脐血中LPO水平显著升高 ,SOD水平显著下降 (P <0 .0 1)。血LPO水平与新生儿体重呈负相关 (P <0 .0 1)。结论　孕妇血及脐血LPO的升高 ,即机体脂质过氧化与IUGR的发生、发展密切相关。     

巨噬细胞与动脉粥样硬化斑块稳定性

为探讨抗氧化剂维生素Ｅ和元素硒对脂质过氧化诱导内此细胞表达细胞粘附分子及单核细胞粘附的影响产胺诱发培养内皮细胞脂质过氧化,检测维生素Ｅ和元素硒对单核细胞会的影响,用免疫组化及共焦显微镜观察维生素Ｅ和元素硒对内此表达血管细胞粘附分子－１及内此细胞白细胞粘附分子－１的影响。结果显示抗氧化剂维生素Ｅ和元素硒可抑制内此脂质过氧化,抑制血管细胞粘附分子－１及内此占附分子－１表达,减少单核细胞粘附。提示抗氧化     

脂质过氧化诱导培养的内皮细胞表达巨噬细胞炎性蛋白1α和血管细胞粘附分子1

为了解脂质过氧化损伤能否诱导内皮细胞表达巨噬细胞炎性蛋白１α和血管细胞粘附分子１ｍＲＮＡ,将培养的内皮细胞随机分为实验组（在培养液中分别加入１μｍｏｌ／Ｌ、５μｍｏｌ／Ｌ及１０μｍｏｌ／Ｌ联胺）和对照组（不加联胺）。用地高辛随机引物标记的人巨噬细胞炎性蛋白１α和血管细胞粘附分子１ｃＤＮＡ探针与各组内皮细胞进行核酸原位杂交。用异硫氰酸胍法提取各组细胞的总ＲＮＡ,与上述探针进行斑点杂交。原位杂交显示,     

铁和乙醇对大鼠肝脏组织脂质过氧化反应的影响

在饲料中添加羰基铁喂养大鼠,形成肝脏内铁含量没的铁过载动物模型,体外研究肝组织内不同的铁含量对乙醇诱导肝组织气体操作折影响,探讨乙醇和铁在诱导肝组织损伤过程中的交互作用。结果显示：饲料中添加铁中明显啬铁在肝脏内的蓄积,肝脏内铁含量随喂养时间而增加,与对照组比较差异有非常显著意义（Ｐ〈０．０１）。肝脏内不同的铁含量均可明显增加乙醇诱导的肝组织脂南过氧化反应。分别与单纯乙醇和相应原单纯铁过载组比较,铁     

体外循环后再灌注氧化及全身炎性反应与肺上皮损伤关系的探讨

[目的]通过建立大鼠开胸停跳体外循环(CPB)模型,并在此基础上通过检测过氧化相关酶及炎性介质,探讨CPB对肺上皮屏障功能损伤的机制。[方法]大鼠CPB的建立Wistar大鼠56只随机分为假手术对照组(Sham-operated group,SH)、体外循环组(cardiopulmonary bypass group,CPB)提取肺组织及血液中炎性介质,进行对比及相关性分析。[结果]CPB组各时相点EVLW均明显升高,与SH组比较差异有统计学意义(P﹤0.05),且以CPB后2h时最高(P﹤0.05),而SH组无明显变化(P﹥0.05)。CPB组肺组织MDA、MPO浓度明显升高,SOD浓度明显降低,与SH组相比较,差异具有统计学意义(P﹤0.05);CPB组血浆TNF-α、IL-6浓度明显升高,IL-10浓度明显降低,与SH组相比较,差异具有统计学意义(P﹤0.05)。[结论]再灌注氧化及全身炎性反应的确与肺上皮损伤存在直接关系。     

Hypertonic saline and reduced peroxynitrite formation in experimental pancreatitis

OBJECTIVES:

In this study, we tested the hypothesis that hypertonic saline exerts anti-inflammatory effects by modulating hepatic oxidative stress in pancreatitis.

INTRODUCTION:

The incidence of hepatic injury is related to severe pancreatitis, and hypertonic saline reduces pancreatic injury and mortality in pancreatitis.

METHODS:

Wistar rats were divided into four groups: control (not subjected to treatment), untreated pancreatitis (NT, pancreatitis induced by a retrograde transduodenal infusion of 2.5% sodium taurocholate into the pancreatic duct with no further treatment administered), pancreatitis with normal saline (NS, pancreatitis induced as described above and followed by resuscitation with 0.9% NaCl), and pancreatitis with hypertonic saline (HS, pancreatitis induced as described above and followed by resuscitation with 7.5% NaCl). At 4, 12, and 24 h after pancreatitis induction, liver levels of inducible nitric oxide synthase (iNOS), heat-shock protein 70, nitrotyrosine (formation of peroxynitrite), nitrite/nitrate production, lipid peroxidation, and alanine aminotransferase (ALT) release were determined.

RESULTS:

Twelve hours after pancreatitis induction, animals in the HS group presented significantly lower iNOS expression (P<0.01 vs. NS), nitrite/nitrate levels (P<0.01 vs. NS), lipid peroxidation (P<0.05 vs. NT), and ALT release (P<0.01 vs. NS). Twenty-four hours after pancreatitis induction, nitrotyrosine expression was significantly lower in the HS group than in the NS group (P<0.05).

DISCUSSION:

The protective effect of hypertonic saline was related to the establishment of a superoxide-NO balance that was unfavorable to nitrotyrosine formation.

CONCLUSIONS:

Hypertonic saline decreases hepatic oxidative stress and thereby minimizes liver damage in pancreatitis.     

Mitochondrial targeting of electron scavenging antioxidants: Regulation of selective oxidation vs random chain reactions

Effective regulation of highly compartmentalized production of reactive oxygen species and peroxidation reactions in mitochondria requires targeting of small molecule antioxidants and antioxidant enzymes into the organelles. This review describes recently developed approaches to mitochondrial targeting of small biologically active molecules based on: (i) preferential accumulation in mitochondria because of their hydrophobicity and positive charge (hydrophobic cations), (ii) binding with high affinity to an intra-mitochondrial constituent, and (iii) metabolic conversions by specific mitochondrial enzymes to reveal an active entity. In addition, targeted delivery of antioxidant enzymes via expression of leader sequences directing the proteins into mitochondria is considered. Examples of successful antioxidant and anti-apoptotic protection based on the ability of targeted cargoes to inhibit cytochrome c-catalyzed peroxidation of a mitochondria-specific phospholipid cardiolipin, in vitro and in vivo are presented. Particular emphasis is placed on the employment of triphenylphosphonium- and hemi-gramicidin S-moieties as two effective vehicles for mitochondrial delivery of antioxidants.     

白细胞过滤减轻心肌过氧化反应及心肌组织损伤

目的探讨低白细胞血灌注对心肌缺血-再灌注过氧化反应及心肌组织损伤的影响。方法成年家猪12只,分成对照组(n=6)和白细胞过滤组(n=6)。两组动物采用相同的体外循环(ECC)及心肌保护液灌注装置。白细胞过滤组在ECC动脉及心肌保护液灌注管路上安装Pall LG-6白细胞滤器,白细胞滤器使用时间为心脏复灌前10 min至ECC结束;心肌保护液灌注均经白细胞滤器。心肌血流阻断60 min后开放升主动脉阻断钳,后并行辅助循环25 min后撤离ECC。结果白细胞过滤显著降低了循环血及心肌保护液中中性粒细胞计数。低白细胞血心肌保护液灌注和缺血后心脏复灌:①显著减少了复灌早期肌酸激酶同工酶及心肌钙蛋白I血浆泄漏;②显著降低了缺血期和复灌早期血浆及心肌组织丙二醛浓度;③对血浆和心肌组织超氧化物歧化酶活力分别有明显和一定程度的抑制作用。结论低白细胞血心肌保护液灌注和缺血后心脏复灌,通过抑制心肌组织过氧化反应显著减轻了心肌组织缺血-再灌注损伤,并对氧自由基清除机制有一定保护作用。     

Chlorpromazine-sensitized photooxidation of squalene

Summary In connection with chlorpromazine-induced skin photosensitivity, chlorpromazine-sensitized photooxidation of squalene was studied in vitro. When squalene (in ethanolic solution or in an aqueous suspension) was irradiated with UV-A light in the presence of chlorpromazine, the yield of peroxidation products was greatly increased. Lines of evidence for the peroxidation were obtained by the iodometric determination and the thiobarbituric-acid method. Gas chromatography indicated that squalene was decomposed by the photosensitized reaction and the remaining amount was decreased exponentially with increasing fluence. The quenching effects of NaN₃ and 2,5-dimethylfuran and the enhancing effect of D₂O showed participation of singlet oxygen in the photosensitized reaction.