黄芩甙对重症急性胰腺炎大鼠胰腺氧化应激的保护作用

目的探讨黄芩甙对大鼠重症急性胰腺炎（SAP）氧化应激的保护作用。方法45只大鼠随机分为假手术组、模型组和黄芩甙干预组,每组15只。假手术组进腹后仅翻动胰腺和十二指肠后关腹,不给予任何干预,模型组、黄芩甙干预组采用3.5%牛磺胆酸钠逆行胰胆管注射制造SAP大鼠模型。黄芩甙干预组在造模成功后给予黄芩甙治疗,其余两组给予等量生理盐水。术后3h、6 h及12 h,测定各组大鼠血清淀粉酶的水平及胰腺组织MDA、SOD及MPO的含量,免疫组化法检测胰腺组织聚腺苷二磷酸核糖（PAR）及硝基酪氨酸的表达。结果术后3 h、6 h及12 h,模型组血清淀粉酶较假手术组显著增高（P〈0.01）,黄芩甙干预组血清淀粉酶显著降低于模型组（P〈0.01）;术后各时间点,黄芩甙干预组胰腺组织MDA、MPO含量显著低于模型组（P〈0.01）;SOD水平显著高于模型组（P〈0.01）;术后各时间点,假手术组胰腺组织均无PAR及硝基酪氨酸表达,模型组PAR及硝基酪氨酸表达阳性,且随时间延长表达增多,黄芩甙干预组PAR及硝基酪氨酸表达均低于模型组,且随时间延长显著减少。结论黄芩甙可能通过降低胰腺炎的氧化应激水平,减轻胰腺炎症程度而发挥对胰腺炎的保护作用。     

Cytoprotective effects of amifostine,ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

AIM:To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine(NAC),amifostine(AMF)and ascorbic acid(ASC)in methotrexate(MTX)-induced hepatotoxicity.METHODS:An MTX-induced hepatotoxicity model was established in 44 male Sprague Dawley rats by administration of a single intraperitoneal injection of20 mg/kg MTX.Eleven of the rats were left untreated(Model group;n=11),and the remaining rats were treated with a 7-d course of 50 mg/kg per day NAC (MTX+NAC group;n=11),50 mg/kg per single dose AMF(MTX+AMF group;n=11),or 10 mg/kg per day ASC(MTX+ASC group;n=11).Eleven rats that received no MTX and no treatments served as the negative control group.Structural and functional changes related to MTX-and the various treatments were assessed by histopathological analysis of liver tissues and biochemical assays of malondialdehyde(MDA),superoxide dismutase(SOD),catalase,glutathione(GSH)and xanthine oxidase activities and of serum levels of aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase and total bilirubin.RESULTS:Exposure to MTX caused structural and functional hepatotoxicity,as evidenced by significantly worse histopathological scores[median(range)injury score:control group:1(0-3)vs 7(6-9),P=0.001]and significantly higher MDA activity[409(352-466)nmol/g vs 455.5(419-516)nmol/g,P<0.05].The extent of MTX-induced perturbation of both parameters was reduced by all three cytoprotective agents,but only the reduction in hepatotoxicity scores reached statistical significance[4(3-6)for NAC,4.5(3-5)for AMF and 6(5-6)for ASC;P=0.001,P=0.001 and P<0.005vs model group respectively].Exposure to MTX also caused a significant reduction in the activities of GSH and SOD antioxidants in liver tissues[control group:3.02(2.85-3.43)μmol/g and 71.78(61.88-97.81)U/g vs model group:2.52(2.07-3.34)μmol/g and 61.46(58.27-67.75)U/g,P<0.05];however,only the NAC treatment provided significant increases in these antioxidant enzyme activities[3.22(2.54-3.62)μmol/g and 69.22(61.13-100.88)U/g,P<0.05 and P<0.01vs model group respectively].CONCLUSION:MTX-induced structural and functional damage to hepatic tissues in rats may involve oxidative stress,and cytoprotective agents(NAC>AMF>ASC)may alleviate MTX hepatotoxicity.     

脉络宁抑制氧化应激保护缺血性脑损伤

目的 探讨脉络宁对氧化应激和缺血性脑损伤的影响.方法 健康雄性昆明小鼠126只,分为假手术组(n=18)、生理盐水对照组(n=54)和脉络宁组(n=54).建立大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型,脉络宁组和生理盐水对照组MCAO 2 h后分别经尾静脉给予脉络宁注射液和同体积生理盐水,然后每隔24 h重复1次.在MCAO 12、24和72 h分别进行神经功能评分、脑水含量、梗死体积、膜电位以及蛋白质氧化应激代谢产物3-硝基酪氨酸(3-nitrotyrosine,3-NT)、脂质氧化应激代谢产物4-羟基壬烯醛(4-hydroxy-2-nonenal,HNE)和核酸氧化应激代谢产物8-羟基脱氧鸟苷(8-hydroxy-2'-deoxyguanosine,8-OHdG)检测.结果 在脑缺血后不同时间点,脉络宁注射液均可显著改善脑缺血小鼠的神经功能、减轻脑水肿和缩小梗死体积,其中以72 h最为显著;脉络宁注射液可逆转脑皮质和内囊区的线粒体膜电位降低,显著下调缺血后皮质、内囊和血清3-NT、HEN 和8-OHdG的升高,其中以降低HNE效果最为显著.结论 脉络宁注射液能有效保护小鼠缺血性脑损伤,其机制与抑制氧化应激,尤其是抗脂质氧化有关.     

氟中毒与氧化应激

复习了氟中毒与氧化应激关系的有关文献。从近年来多数研究资料来看,氟中毒的一定阶段确可发生自由基增高和氧化应激反应,但要确定氧化应激与氟化物所致各种损害之间的因果联系,则还有许多工作要做。     

微生物源性抗氧化剂对diquat诱导的小鼠肝脏氧化应激、内质网应激和功能的影响

目的以diquat诱导的小鼠氧化应激为模型,研究微生物源性抗氧化剂(MA)对小鼠肝脏氧化应激、内质网应激、细胞凋亡和功能的影响。方法选择体质量16~18 g的C57BL/6雌性小鼠18只,随机分为3组,每组6只。抗氧化剂组小鼠灌胃MA,对照组和模型组小鼠灌胃等量等渗盐水,饲养22 d后,模型组和抗氧化剂组腹腔注射diquat溶液,对照组小鼠注射等量等渗盐水,处理3h后处死小鼠采集肝组织。肝脏组织制成10%匀浆后,依据试剂盒说明书检测自由基含量、丙二醛(MDA)含量、抗氧化酶活性、天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)活性,用qRT-PCR检测内质网应激和细胞凋亡相关基因表达情况。肝脏组织制成10%匀浆后,依据试剂盒说明书检测自由基含量、丙二醛(MDA)含量、抗氧化酶活性、天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)活性,用qRT-PCR检测内质网应激和细胞凋亡相关基因表达情况。多组间数据比较采用单因素方差分析。结果过氧化氢在对照组、模型组、抗氧化剂组分别为(8.74±1.38)、(11.44±1.01)、(9.81±0.98)mmol/g,组间比较差异有统计学意义(F=7.640,P<0.05)。对照组、模型组和抗氧化剂组MDA的含量分别为(0.65±0.07)、(0.86±0.18)、(0.70±0.05)nmol/mg,组间比较差异有统计学意义(F=5.406,P<0.05)。模型组AST活性为(146.68±4.29)U/g,显著高于对照组的(125.64±15.69)U/g与抗氧化剂组的(126.57±1.82)U/g,F=6.192,P<0.05。实时定量PCR结果显示,与对照组相比,模型组蛋白激酶R样内质网激酶(PERK)和活化转录因子6(ATF6)基因相对表达量显著升高,分别为1.880±0.442和1.800±0.380(F值分别为7.702、10.815,P值均<0.05);与模型组相比,抗氧化剂组PERK和ATF6基因相对表达量显著降低,分别为1.310±0.333、1.180±0.204(P值均<0.05)。细胞凋亡相关基因表达结果显示,抗氧化剂组caspase3和caspase8基因相对表达量分别为1.136±0.381、1.593±0.407,与模型组的1.572±0.127和2.843±0.973相比,显著降低(F值分别为12.800、7.657,P值均<0.05)。结论微生物源性抗氧化剂减弱diquat诱导的小鼠肝脏氧化应激、内质网应激和肝细胞凋亡,改善肝脏功能。     

Changing face of hepatic encephalopathy: Role of inflammation and oxidative stress

The face of hepatic encephalopathy(HE) is changing.This review explores how this neurocognitive disorder,which is associated with both acute and chronic liver injury,has grown to become a dynamic syndrome that spans a spectrum of neuropsychological impairment,from normal performance to coma.The central role of ammonia in the pathogenesis of HE remains incontrovertible.However,over the past 10 years,the HE community has begun to characterise the key roles of inflammation,infection,and oxidative/nitrosative s...     

Phosalone-induced inflammation and oxidative stress in the colon: evaluation and treatment

AIM: To investigate the side effects of phosalone on intestinal cells and to evaluate benefits of ellagic acid(EA) as a remedy.METHODS: In order to conduct an in vivo study, a rat model was used. The rats were divided into ten groups based on the materials used in the experiment and their dosage. The first group was fed normally. The second group was administered EA through gavage. Next Four groups were given(1/3, 1/5, 1/10, 1/20) LD50 phosalone; an organophosphorus compound. The last four groups received(1/3, 1/5, 1/10, 1/20) LD50 phosalone and of EA. After one month, the rats were sacrificed and their colon cells were examined to evaluate the level of inflammation, proteins and oxidative stress markers.RESULTS: The results of this research show that phosalone elevates oxidative stress and changes the level of tumor necrosis factor-a(TNF-α), interlukin-6β(IL-6β) and nuclear factor(NF)-κB proteins. EA administration reduced phosalone toxicity and changed oxidative stress and inflammatory markers for all phosalone doses. Overall changes in reduction of TNF-α(230.47 ± 16.55 pg/mg protein vs 546.43 ± 45.24 pg/mg protein, P 0.001), IL-6β(15.85 ± 1.03 pg/mg protein vs 21.55 ± 1.3 pg/mg protein, P 0.05), and NF-κB(32.47 ± 4.85 pg/mg protein vs 51.41 ± 0.71 pg/mg protein, P 0.05) manifest that the efficacy of EA is more viable for 1/3 LD50 dose of phosalone. Furthermore, EA is effective to counteract the negative outcomes of oxidative stress. When EA was used to treat 1/3 LD50 of phosalone's side effects, it improved the level of ACh E activity(48.5% ± 6% vs 25% ± 7%, P 0.05), TTM(0.391 ± 0.008 mmol/L vs 0.249 ± 0.032 mmol/L, P 0.05), FRAP(46.04 ± 5.005 μmol/L vs 18.22 ± 1.9 μmol/L, P 0.01) and MPO(0.222 ± 0.019 U/mg protein vs 0.387 ± 0.04 U/mg protein, P 0.05). CONCLUSION: This research highlights that EA is effective to alleviate the side effects of phosalone by reducing the level of oxidative stress and inflammatory proteins.     

Mechanisms of oxidative stress and myocardial protection during open-heart surgery

Cold heart protection via cardioplegia administration, limits the amount of oxygen demand. Systemic normothermia with warm cardioplegia was introduced due to the abundance of detrimental effects of hypothermia. A temperature of 32–33°C in combination with tepid blood cardioplegia of the same temperature appears to be protective enough for both; heart and brain. Reduction of nitric oxide (NO) concentration is in part responsible for myocardial injury after the cardioplegic cardiac arrest. Restoration of NO balance with exogenous NO supplementation has been shown useful to prevent inflammation and apoptosis. In this article, we discuss the “deleterious” effects of the oxidative stress of the extracorporeal circulation and the up-to-date theories of “ideal” myocardial protection.     

A novel mechanism of action for statins against diabetes-induced oxidative stress

Aims/hypothesis Atorvastatin exerts beneficial vascular effects in diabetes, but the underlying mechanisms are yet to be elucidated. The aim of the present study was to determine whether Rac-1 is involved in the effect of atorvastatin on oxidative stress and vascular dysfunction. Materials and methods Using human aortic endothelial cells (HAECs) we evaluated the effect of high glucose levels on peroxide production by dihydrodichlorofluorescein and on Rac-1 activity using immunocytochemistry to detect Rac-1 translocation to the membrane. We evaluated vascular function, peroxide production by dihydroethidium and NADPH oxidase activity in vessels from atorvastatin-treated mice. Rac-1 activity was also assessed, both by immunoprecipitation of the Rac–p21-activated kinase complex and by analysis of Rac-1 translocation to the membrane. These experiments were also conducted in vessels infected with an adenoviral vector carrying a constitutively active mutant of Rac-1. Results In HAECs exposed to high glucose levels, atorvastatin prevented oxidative stress, and this protection was associated with impaired Rac-1 activation. This effect was also observed in a murine model of diabetes mellitus. More importantly, the addition of geranylgeranyl pyrophosphate (GGPP) blocked the effects of atorvastatin in both glucose-exposed HAECs and diabetic vessels. Atorvastatin failed to afford protection against vascular abnormalities in the presence of a constitutively active mutant of Rac-1. Conclusions/interpretation The results of this study demonstrate that the vascular antioxidant effect of atorvastatin in diabetes is mediated through inhibition of Rac-1 via a reduction in GGPP. Thus, selective Rac-1 inhibition should be considered in the design of novel pharmacological strategies to reduce the impact of diabetes mellitus on vascular function.     

瑞舒伐他汀联合普罗布考对大鼠动脉粥样硬化炎症与氧化应激的干预效果

目的观察瑞舒伐他汀联合普罗布考对大鼠动脉粥样硬化炎症及氧化应激相关指标的干预效果。方法雄性Wistar大鼠54只随机分5组,正常组(A组,n=12)、模型组(B组,n=12)、瑞舒伐他汀组(C组,n=10)、普罗布考组(D组,n=10)、瑞舒伐他汀加普罗布考组(E组,n=10)。A组普通饲料喂养,B组及药物干预组高脂饲料喂养同时给予卵清白蛋白(2.5 mg/kg)腹腔注射(5次/周)。从第9周开始,C、D、E组给予药物干预,C组给予瑞舒伐他汀5 mg/kg.d灌胃,D组给予普罗布考500 mg/kg.d灌胃,E组给予瑞舒伐他汀5 mg/kg.d+普罗布考500 mg/kg.d灌胃,A、B组给予生理盐水灌胃作为对照,连续干预8周。第16周末,所有大鼠称重,麻醉,开胸经右心房取血,留取血清。随后用ELISA法检测血清炎症指标血管内皮细胞钙黏蛋白(VE-cadherin)、脂联素(APN)及氧化应激指标8-异前列腺素-F2a(8-iso-PGF2a)、超氧化物歧化酶(SOD)表达水平。同时留取主动脉,进行HE染色,观察主动脉病理组织学变化。结果与正常组比较,模型组和药物干预组血清VE-cadherin、8-iso-PGF2a水平显著升高(P0.01),APN、SOD水平显著降低(P0.01),血管内膜增厚(P0.05),内皮细胞排列紊乱,可见泡沫细胞和单核细胞,且细胞间隙增宽。与B组比较,C、D、E组血清VE-cadherin、8-iso-PGF2a水平明显降低(P0.01),APN、SOD表达升高(P0.05),血管壁内膜厚度变薄(P0.01)。与C组比较,D、E组血清8-iso-PGF2a水平下降(P0.01),SOD水平升高(P0.01);与C组比较,E组血清VE-cadherin降低(P0.01),APN升高(P0.01)。与D组比较,E组血清VE-cadherin降低(P0.05),APN升高(P0.05);与C、D组比较,E组血管内膜变薄(P0.05)。结论瑞舒伐他汀与普罗布考均具有抗炎和抗氧化作用,普罗布考的抗氧化作用优于瑞舒伐他汀,两药联合应用可明显降低血清VE-cadherin的表达,并提高APN的表达,减轻主动脉血管内膜的损伤,改善动脉粥样硬化。     

黄芩苷对体外氧化应激模型中肝型脂肪酸结合蛋白表达的影响及其意义

目的 研究黄芩苷对体外氧化应激模型中肝型脂肪酸结合蛋白(L-FABP)表达的影响及其意义. 方法 用终浓度为400 μ mol/L的过氧化氢(H2O2) 37℃避光孵育细胞20min,建立体外诱导氧化应激模型.应用甲基噻唑基四唑法(MTT)检测不同浓度黄芩苷作用细胞的存活率,确定24h、48 h黄芩苷的半数中毒浓度(TC50).流式细胞技术检测不同浓度黄芩苷(25、50、100μmol/L)作用后活性氧(ROS)的表达、细胞内超氧化物歧化酶(SOD)和谷胱甘肽(GSH)活性变化,实时PCR和Western blot检测肝细胞内L-FABP基因和蛋白表达.数据分析采用单因素方差分析.结果 根据MTT法得出25、50、100 μ mol/L的黄芩苷作用于细胞24h的存活率为83.60％±3.47％,72.36％±2.18％,70.16％±2.04％,F值为386.24,P＞0.05;作用于细胞48h的存活率为84.93％±3.11％,76.16％±2.45％,72.72％±2.31％,F值为475.92,P＞0.05.直线回归法得出黄芩苷持续作用24h和48h的TC50分别为153.2、170.6μmol/L.在此范围内,用25、50、100μmol/L浓度的黄芩苷分别作用Chang肝细胞24、48 h后,ROS含量24 h分别为37.0±3.30,22.90±3.84,29.60±2.52,F值为70.06,P＜0.05 ; 48h分别为35.77±2.35,21.80±3.10,23.87±1.98,F值为110.92,P＜0.05,而400μ mol/L H2O2组ROS含量24h和48h分别为45.50±3.47,48.80±2.70,以50μmol/L的黄芩苷作用48h效果最为显著.用50μmol/L黄芩苷处理48h后细胞内SOD活性为(51.53±1.91)μ g/mg,GSH为(49.85±1.45) U/mg;与对照组SOD为(26.36±1.23)μ g/mg,GSH为(25.11±1.74) U/mg,F值分别为93.81和92.51,P值均＜0.05).尽管50μmol/L黄芩苷处理48 h后细胞内L-FABP在mRNA水平并无明显变化,但50μmol/L黄芩苷处理48 h后细胞内L-FABP蛋白表达与对照组相比增加约80％.结论 黄芩苷能通过增强L-FABP蛋白表达,增加细胞内SOD和GSH的活性发挥抗氧化作用.     

阿托伐他汀对高胆固醇-动脉粥样硬化兔脑组织的抗氧化应激作用研究

目的建立兔高胆固醇-动脉粥样硬化模型，观察阿托伐他汀对脑组织的抗氧化应激保护作用。方法24只健康新西兰白兔随机分为3组：（A组）正常对照组、（B组）高脂饮食组和（C组）高脂饮食加阿托伐他汀组。喂饲8周后，测定兔血清总胆固醇（TC）及低密度脂蛋白（LDL）浓度，取脑组织检测血红素氧合酶（HO-1）水平、超氧化物歧化酶（SOD）活力及丙二醛（MDA）含量的变化。结果ABC三组HO-1平均吸光度值分别为0．418200±0．001874，0．682100±0．001853，0．918800±0．001549；SOD值分别为424．03±14．45、271．79±13．46和402．38±7．35；MDA值分别为16．66±2．55、40．87±2．78和21．57±2．19。与对照组相比，高脂饮食组HO-1表达显著上调，SOD活力下降，MDA含量增加（P〈0．05）；阿托伐他汀组较高脂饮食组HO-1表达进一步上调，SOD活力升高，MDA含量降低（P〈0．05）。结论兔动脉粥样硬化过程中，脑组织处于氧化应激状态，阿托伐他汀可对抗氧化应激损伤，从而减缓动脉粥样硬化的形成。     

急性胰腺炎与氧化应激

氧化应激是在机体内活性氧生成和抗氧化物质失衡状态下,直接或间接通过信号转导通路引起细胞的损伤,是许多疾病的病因,同时又是许多疾病发生、发展的结果.研究表明,氧化应激在急性胰腺炎的发病中发挥重要作用,还与胰腺炎时胰腺外器官,如心、肝、肺、肾、消化道等的损伤有密切联系.氧化应激产生大量的活性氧和活性氮,引起炎症反应及微循环障碍,通过不同途径引起细胞坏死或凋亡,造成胰腺及其他脏器的功能障碍甚至衰竭.抗氧化剂可减少氧自由基的产生或直接清除机体产生的氧自由基,并增强机体的抗氧化能力,对急性胰腺炎具有较好的治疗作用.     

Reduction in oxidative stress and modulation of heart failure subsequent to myocardial infarction in rats

BACKGROUND:

Patients surviving myocardial infarction (MI) are at a heightened risk for the development of congestive heart failure. This clinical syndrome has been associated with an antioxidant deficit and elevated oxidative stress in the myocardium. Effects of dietary vitamin E, a lipid-soluble antioxidant, on myocardial anti-oxidant enzyme activities, oxidative stress and hemodynamic function, were examined separately in the viable left ventricle (LV) and right ventricle (RV) of rats at 16 weeks post-MI.

METHODS AND RESULTS:

Animals were fed either a basal diet or a diet enriched with 1500 U of vitamin E/kg beginning two weeks before MI-inducing surgery and continued 16 weeks post-MI. In the MI animals on the basal diet, LV systolic pressure (LVSP) and RVSP were significantly depressed and LV end-diastolic pressure (LVEDP) and RVEDP were significantly elevated. These hemodynamic alterations were accompanied by clinical signs of heart failure including dyspnea, lethargy and cyanotic limbs. Supplementation of MI animals with dietary vitamin E resulted in complete normalization of RVSP and RVEDP. An increase in LVSP and a decrease in LVEDP was observed in the vitamin E-supplemented MI animals, although mild residual LV dysfunction remained. The myocardial enzymatic antioxidants catalase and glutathione peroxidase declined substantially in each of the ventricles of unsupplemented MI animals. Myocardial levels of vitamin E were reduced by 33% in the LV and no change was observed in the RV of the MI animals. Vitamin E-supplemented control animals and MI animals showed a significant increase in vitamin E levels in both ventricles. Myocardial oxidative stress, as assessed by lipid peroxidation and the ratio of reduced to oxidized glutathione, was significantly increased in each of the respective ventricles of untreated MI animals. Supplementation with dietary vitamin E resulted in a substantial increase in the myocardial activities of catalase and glutathione peroxidase in both the LV and RV. Furthermore, an increase in the ratio of reduced to oxidized glutathione concomitant with significantly less lipid peroxidation was also observed in each of the respective ventricles of MI animals supplemented with vitamin E. No overt clinical signs of heart failure were evident in these vitamin E-supplemented animals.

CONCLUSIONS:

An improved myocardial redox state and endogenous antioxidant reserve with vitamin E therapy, coupled with the modulation of the development of heart failure, lend strong support in favour of a pathophysiological role for increased oxidative stress in the pathogenesis of heart failure, at least in experimental animals. Association between an increase in oxidative stress and cardiac events in patients requires further examination.     

Potential ergogenic effects of L-arginine against oxidative and inflammatory stress induced by acute exercise in aging rats

In this study, we report protective effects of dietary L-arginine (L-Arg) supplementation against oxidative stress and inflammation in aging rats during exhaustive exercise. Thirty 18-month-old male Sprague-Dawley rats were randomly divided into four groups: sedentary control (SC); sedentary control with L-Arg treatment (SC+Arg); exhaustive exercise (E); and exhaustive exercise with L-Arg treatment (E+Arg). Rats in groups SC+Arg and E+Arg received a 2% L-Arg diet. Rats in groups E and E+Arg performed an exhaustive running test on a treadmill. The mean duration of exercise differed significantly between groups E and E+Arg (51+/-6 versus 63+/-3min). Results showed significant increases in xanthine oxidase (XO) and myeloperoxidase (MPO) activities and in lipid peroxidation end-product (malondialdehyde, MDA) levels of myocardial, muscular, hepatic, pulmonary, and renal tissues of exercised rats compared with SC and SC+Arg rats. The increased XO and MPO activities and MDA levels significantly decreased in exercised rats that were fed a diet supplemented with L-Arg. We also found that L-Arg supplementation prevented exhaustive exercise-induced elevations of plasma aminotransferase activity, and lactate and uric acid levels in aging rats. These findings suggest that L-Arg supplementation enhances exercise capacity and protects against oxidative damage and inflammatory responses caused by exhaustive exercise in aging rats.     

Protective effects of luteolin against oxidative stress and mitochondrial dysfunction in endothelial cells

Background and aimsLuteolin is a common flavonoid that is abundantly present in various edible plants, it is known to exhibit beneficial effects on cardiovascular system. However, the mechanisms which underlie the protective effects of luteolin on endothelial cell damage caused by oxidative stress remains unclear. The purpose of this study is to test the hypothesis which states that luteolin protects against H₂O₂-induced oxidative stress via modulating ROS-mediated P38 MAPK/NF-κB and calcium-evoked mitochondrial apoptotic signalling pathways.Methods and resultsHuman umbilical vein endothelial cells (HUVECs) were pretreated with luteolin prior to being stimulated by 600 μM H₂O₂ for another 24 h. The expression of native and phosphorylated-P38, IκB, NF-κB, native eNOS, phosphorylated-eNOS, iNOS and several apoptosis-related proteins were analyzed by Western blot. In addition, intracellular calcium was determined by fura-2 AM and mitochondrial membrane potential was examined by using JC1. Using the data gathered, we found indications that H₂O₂ induced P38 MAPK/NF-κB activation. H₂O₂ downregulated the expression of eNOS and upregulated iNOS, which in turn contribute to an elevated NO generation and protein nitrosylation. However, pretreatment with luteolin markedly reversed all of these alterations dose-dependently. Additionally, an intracellular calcium rise and subsequent mitochondrial membrane potential collapse, P53 phosphorylation, reduced BcL-2/Bax ratio in the mitochondrial membrane, release cytochrome c from mitochondria, leading to the subsequent activation of caspase 3 activation by H₂O₂ were all markedly suppressed in the presence of luteolin.ConclusionResults from this study may provide the possible molecular mechanisms underlying cardiovascular protective effects of luteolin.     

氧化应激对人淋巴细胞端粒长度的影响

目的　探讨人外周血淋巴细胞遭受过氧化氢 (H2O2 )损伤时,端粒长度的变化。　方法　体外培养人外周血淋巴细胞,分为正常对照组、氧化组和抗氧化组,然后应用Southern杂交技术检测不同时间端粒长度的变化。　结果　端粒长度随着时间的变化表现为缩短;且 3组之间均有显著差异(P<0 .05)。　结论　氧化应激在一定程度上可以引起人淋巴细胞端粒长度的缩短;维生素C具有一定的抗氧化作用,它能减低过氧化损伤,从而减缓端粒缩短的速率。     

Diabetes and dyslipidaemia are associated with oxidative stress independently of inflammation in long-term antiretroviral-treated HIV-infected patients

AimAgeing HIV-infected patients controlled by antiretroviral therapy (ART) frequently present age-related comorbidities, such as cardiovascular (CV) events, diabetes, dyslipidaemia, hypertension and chronic kidney disease (CKD). The prevalence of these comorbidities was evaluated in a cohort of long-term-monitored ART-controlled HIV-infected patients, then followed by a search into whether oxidative stress, like inflammation, might be associated with metabolic parameters and/or comorbidities.MethodsIncluded were 352 long-term ART patients who started with protease inhibitors (PIs) in 1997–1999. They were evaluated at their final visit, 11 years later, for previous CV events, prevalence of diabetes, LDL-related and atherogenic (high TG/HDL) dyslipidaemias, hypertension and CKD. Also measured were circulating biomarkers to explore oxidative stress (Lp-PLA2, oxLDL, oxLDL/LDL ratio, paraoxonase and arylesterase activities), inflammation/immune activation (hsCRP, hsIL-6, D dimer, soluble CD14, β2 microglobulin, cystatin C), adipokines and insulin resistance. Levels were compared in patients with and without each comorbidity or condition using non-parametric correlation tests and multivariate adjusted analyses.ResultsAt the final visit, 81.5% of patients were male and were aged (median, IQR) 49 years (45–56); BMI was 23.0 kg/m² (21.1–25.4), CD4+ lymphocytes were 620 cells/mm³ (453–790) and 91.5% had undetectable HIV-1 viral loads. The prevalence of diabetes was 11%, and LDL-related dyslipidaemia 28%, atherogenic dyslipidaemia 9%, hypertension 28%, CKD 9% and previous CV events 9%. Diabetes and atherogenic dyslipidaemia were associated with increased oxidative stress and independently with inflammation. LDL-related dyslipidaemia and impaired fasting glucose were associated with increased oxidative stress. No association of these biomarkers was detected with hypertension, CKD and previous CV events.ConclusionIn long-term-treated HIV-infected patients with frequent comorbid conditions, oxidative stress could be contributing to diabetes and LDL-related and atherogenic dyslipidaemias independently of inflammation.