砷中毒所致氧化应激与肝脏损伤

砷中毒是地球化学性疾病，由于砷广泛存在于自然界中，人类接触砷的机会很多。其中，饮用含砷水及敞烧含砷量高的燃煤是我国引发地方性砷中毒的主要原因。砷可引起皮肤癌、膀胱癌、肺癌等多种癌症。近期的研究表明．砷对于肝脏能构成多种损害．如肝纤维化、肝癌。砷中毒致病机制目前尚无成熟、完善的理论解释，氧自由基损伤可能为其重要机制之一，下面从这一角度进行综述。[第一段]     

MTH2蛋白在快速老化P8小鼠海马中表达的增龄性变化

目的 观察8氧鸟嘌呤脱氧核苷三磷酸酶同源蛋白2(MTH2)在快速老化P8小鼠(SAMP8)海马中的表达,探讨其与SAMP8增龄性变化的关系.方法 该实验选用1、4、8、12月龄的SAMP8及同龄的抗快速老化R1小鼠(SAMRl)作为实验对象,每组8只,用免疫组化和免疫印迹法分别检测海马中MTH2蛋白的表达.结果 免疫组化结果显示,MTH2主要在SAMP8神经元胞浆内表达;海马不同区域均有表达,尤以CA1和CA3区表达最多.定量结果显示,SAMR1海马各区域MTH2的表达随增龄无显著性改变;而在SAMP8MTH2的表达随月龄增加而下降,8月龄海马CAl区的吸光度值(A值)为0.0473、CA3区为0.0510,显著低于4月龄海马CA1区的0.0619、CA3区的0.0680;12月龄海马CA1区的A值为0.0369、CA3区为0.0465,显著低于8月龄;8月和12月龄A值SAMP8分别显著低于同龄的SAMR1(P＜0.05).免疫印迹结果显示,4～12月龄SAMP8海马内MTH2表达的灰度值(grey level)分别为0.529、0.313、0.032,显著低于同龄SAMR1(P＜0.05).结论 MTH2蛋白的表达量在SAMP8随增龄而下降,8月龄和12月龄SAMP8的MTH2蛋白表达量与同龄对照组比较差异有统计学意义,提示MTH2蛋白表达量的减少与SAMP8的快速老化相关.     

快速老化小鼠P8肾脏衰老的病理特点

目的 观察快速老化小鼠P8(SAMP8)肾脏病理结构改变.方法 以9月龄SAMP8为衰老动物模型,同龄抗快速老化小鼠R1(SAMR1)为对照,通过PAS、Masson染色及衰老相关β-半乳糖苷酶 (SA-β-gal) 组织化学染色观察肾脏组织病理的改变,免疫组化方法比较肾小管间质细胞外基质 (ECM)成分--纤维连接蛋白 (FN)、Ⅲ型胶原(Col Ⅲ)的变化.结果 9月龄SAMP8小鼠光镜下肾脏病理表现为小管间质纤维化、局灶节段性肾小球硬化等,以小管间质损害较为显著;SA-β-gal染色阳性细胞显著增加;免疫组化结果显示FN、ColⅢ在肾小管间质过度沉积.上述改变与SAMR1组相比,差异有显著性.结论 SAMP8肾脏的病理改变符合肾脏衰老的特点.     

老年比格犬肝脏组织学与超微结构的变化

目的：研究老年比格犬肝脏的组织学与超微结构变化。方法将15只犬龄1．5～10．6岁的国际标准试验用健康比格犬,按犬龄分为中青年组和老年组。老年组7只,平均犬龄为（8．26±1．52）岁;中青年组8只,平均犬龄为（2．21±0．94）岁。予以静脉麻醉后取肝脏组织,HE 染色后在光学显微镜下观察比较两组肝细胞数目、肝细胞形态及间质情况;在电子显微镜下观察比较两组肝细胞内线粒体数量密度、形态和面积分数,内质网形态和面积分数,微粒体数量密度和形态,肝血窦内皮细胞的厚度和窗孔密度（即单位长度窗孔的数目）和直径,脂褐素的形态和数量密度等。两组间比较采用独立样本的 t 检验。结果光学显微镜下观察,肝细胞围绕中央静脉呈放射状排列,尤以中青年组明显,肝细胞呈圆形或椭圆形,以单核或双核细胞居多,中青年组肝细胞胞质呈致密的淡红色,空泡状脂滴小而少见,细胞边界清楚;老年组肝细胞胞质空泡化明显,可见较大的空泡状脂滴,胞质内散在嗜酸性颗粒,细胞边界模糊,肝细胞数目较中青年组明显减少[（75．80±5．76）／高倍视野比（97．80±6．45）／高倍视野,t＝－2．510,P ＝0．026]。中青年组及老年组比格犬肝组织内均未见明显炎性细胞浸润。老年组较中青年组细胞间隙增大、细胞外间质增多。电子显微镜下观察,正常肝细胞内线粒体呈双膜的椭圆形、圆形或马蹄状,其内可见嵴,主要分布在细胞核周围。与中青年组相比,老年组肝细胞内线粒体形态多变,线粒体数量密度较中青年组明显减少[（0．202±0．021）／μm2比（0．248±0．040）／μm2,t ＝－2．683,P ＝0．020],面积分数较中青年组明显减少（0．136±0．015比0．202±0．019,t＝－6．083,P ＜0．01）;内质网呈网状叠状排列,散在片状分布,细胞核周围较为多见,呈扁平状或堆积状,老年组肝细胞内质网面积分数较中青年组明显减少（0．006±0．001比0．011±0．004,t＝－3．338,P ＝0．005）;肝细胞内脂褐素呈无膜的圆形或不规则结构,其内色素分布不均,老年组脂褐素数量密度显著高于青年组（0．028±0．025比0．001±0．000,t＝2．880,P ＝0．014）;老年组微粒体数目略少于中青年组,差异无统计学意义（P ＝0．603）。老年组肝血窦内皮细胞厚度较中青年组明显增加（0．242±0．047）μm 比（0．114±0．075）μm,t ＝3．881,P ＝0．002）;老年组内皮细胞之间窗孔直径和窗孔密度[（1．895±0．439）μm和（0．260±0．120）／μm]较中青年组[（3．186±0．332）μm 和（0．723±0．184）／μm]明显减少（t＝6．345、－4．511,P 均＜0．01）。结论老年肝脏的质和量都发生了一系列退化,这些退化表现是老年肝脏储备功能降低的结构基础,也是老年人肝脏疾病高发的直接或间接原因。     

柴胡煎剂治疗肝脏缺血性损伤的形态学观察

目的研究大鼠肝脏缺血性损伤后肝组织的病理学改变,以及柴胡煎剂的治疗作用.方法建立大鼠肝门完全阻断的模型,观察肝脏缺血性损伤后柴胡组和普食组在不同的时间阶段光镜和电镜下肝组织的病理学改变.结果电镜观察发现,术后1 d各组肝窦内皮细胞孔隙加大,内皮破坏,内皮之间可见孔道,内皮细胞核内染色质浓聚,核膜仍完整;肝细胞肿胀,线粒体明显肿胀,基质变化,粗面内质网肿胀,脱颗粒,粗面内质网增多,细胞内糖原减少,细胞内溶酶体增多.细胞膜特化部分如桥粒、毛细胆管区微绒毛有轻微破坏.术后4 d普食组肝窦内皮细胞孔隙大,内皮细胞核内染色质浓集于核膜;肝细胞肿胀,线粒体肿胀,基质密度变淡,内嵴结构模糊;粗面内质网排列不规则,脱颗粒,细胞膜破裂,肿胀变性的细胞器游离于胞外.柴胡组肝细胞轻度肿胀,核形态规则,出现吞饮小泡,肝细胞线粒体轻度肿胀,结构模糊,部分粗面内质网轻度扩张,糖原颗粒减少,可见溶酶体及脂滴,内皮膜欠光滑,基底部与肝细胞膜联系欠紧密.术后7 d普食组肝细胞仍见轻度肿胀,线粒体轻度肿胀,结构模糊,基质变化,其内嵴变短,膜结构欠清楚;粗面内质网排列欠规则,糖原颗粒较少,可见少量溶酶体及脂滴.内膜欠完整,基底部与肝细胞联系欠紧密.柴胡组肝细胞未见肿胀,基本恢复到正常形态与结构.光镜下组织形态学的改变与电镜所见一致.结论柴胡煎剂具有促进肝细胞再生,修复损伤的能力,对肝脏缺血性损伤有保护作用,为临床上柴胡在肝脏外科围手术期的应用奠定了病理学基础.     

快速老化小鼠SAMP10的NF-E2 YB-1LRG47基因表达与脑衰老的相关性

目的探讨SAMP10小鼠NF-E2、YB-1、LRG47基因表达与脑衰老的相关性.方法采用快速老化小鼠SAMP10、SAMR1为模型,运用RT-PCR和地高辛标记的非放射性Northernblot技术,观察8月龄SAMR1对照组、SAMP10组前脑、皮质和海马NF-E2、YB-1、LRG47基因表达的变化. 结果SAMP10组在前脑、皮质、海马中NF-E2的表达(0.58±0.16、0.60±0.11、0.61±0.10)、YB-1的表达(0.48±0.13、0.47±0.11、0.46±0.10)、LRG47的表达(0.55±0.08、0.54±0.12、0.56±0.14)与SAMR1对照组在前脑、皮质、海马中NF-E2(0.36±0.09、0.41±0.10、0.38±0.10)、YB-1(0.33±0.09、0.30±0.08、0.31±0.11)、LRG47(0.40±0.10、0.38±0.09、0.37±0.07)的表达比较,均明显下调(P＜0.05).结论SAMP10小鼠脑衰老与转录调节因子NF-E2、YB-1、LRG47基因表达异常有关.     

催老小鼠重要脏器氧化水平和抗氧化能力的变化

目的　研究D 半乳糖催老小鼠心、肝、脑、肺、肾等重要脏器氧化水平和抗氧化能力的改变 ,并对其进行比较。　 方法 　 2 0只 2月龄雄性小鼠随机分为催老组和正常对照组 ;催老组每日皮下注射D 半乳糖 10 0mg·kg-1,正常对照组每日皮下注射等量生理盐水 ,持续 42d。以丙二醛 (MDA)含量反映氧化水平 ,超氧化物歧化酶(SOD)活性反映抗氧化能力。　 结果 　与正常对照组相比 ,D 半乳糖催老组小鼠心、肝、脑、肺、肾等重要脏器MDA含量明显增加 (P <0 0 1) ;肝、脑、肺和肾的SOD活性显著降低 (P <0 0 5 ) ,而心脏SOD活性无明显变化。　 结论　D 半乳糖催老小鼠心、肝、脑、肺、肾等重要器官氧化水平增加 ;肝、脑、肺、肾等器官抗氧化水平下降 ;各器官在改变程度上存在一定差异     

中药虎杖对大鼠肝脏缺血性损伤保护的形态学观察

目的研究中药虎杖煎剂在治疗大鼠肝脏缺血性损伤后肝组织的病理学改变,证实该药对急性肝脏缺血性损伤有治疗作用.方法建立大鼠常温下肝门完全阻断的模型,观察肝脏缺血损伤后虎杖组和普食组在不同的时间段肝组织的病理学改变.结果通过光镜和电镜发现,术后1 d普食组与虎杖组肝细胞肿胀,结构破坏,肝窦内皮细胞孔隙加大,内皮破坏,内皮之间可见孔道.术后4 d普食组肝小叶结构仍破坏,线粒体肿胀,颗粒变性.而虎杖组未见肝细胞坏死改变,细胞膜特化部分如桥粒、毛细胆管区微绒毛有轻微破坏.术后7 d普食组肝细胞变性仍可见,线粒体轻度肿胀,基质变化,膜结构欠清楚,粗面内质网欠规则.而虎杖组肝细胞基本恢复正常形态.结论虎杖煎剂具有改善损伤肝组织的微循环,抑制白细胞、血小板与肝脏内皮细胞的粘附,达到促进肝细胞再生、修复损伤的能力.为临床上肝脏外科围手术期的应用奠定了病理学基础.     

肝苏对CCl4肝纤维化大鼠氧化应激和胶原表达的影响术

前期体外实验发现肝苏具有肝细胞保护、抗氧化、抗肝纤维化作用。目的：探讨肝苏对实验性大鼠肝纤维化的防治作用。方法：以四氯化碳（CCI。）诱导大鼠肝纤维化模型。63只Sprague-Dawley（SD）大鼠随机分为正常对照组（7只）、肝纤维化模型组（14只）、低剂量肝苏干预组（1g／kg,14只）、中剂量肝苏干预组（2g／kg,14只）、高剂量肝苏干预组（4g/kg,14只）。检测各组大鼠血清肝生化指标和透明质酸（HA）水平以及肝组织丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性．HE和Masson染色观察肝组织纤维化程度,免疫组化染色检测肝组织肝星状细胞（HSC）活化标记d．平滑肌肌动蛋白（0I-SMA）以及I型、Ⅲ型胶原含量。结果：大鼠肝纤维化模型建立成功。各剂量肝苏干预组血清AIJT、AST、ALP、HA水平较模型组不同程度地下降;肝组织MDA含量较模型组下降,高、中剂量组差异显著,但SOD活性无明显变化：肝组织纤维化程度较模型组改善．尤以高剂量组为著;肝组织a-SMA、I型、Ⅲ型胶原含量较模型组减少,前两者减少更为明显。结论：肝苏能减轻实验性大鼠肝纤维化的肝细胞损伤,降低肝组织MDA含量,抑制HSC活化和肝内胶原合成,具有抗氧化和抗纤维化作用。     

Reduced antioxidant level and increased oxidative damage in intact liver lobes during ischaemia-reperfusion

AIM:To determine whether increased blood flow of theliver can cause oxidative stress and hepatocyte damage,and to elaborate methods suitable for measuring theantioxidant defence during hepatic surgery on rat model.METHODS:In nembutal narcosis,the left lateral andthe medial lobes of the liver were clipped for 45 minto make the total blood supply flow through the otherlobes.Total antioxidant status,glutathione peroxidaseand superoxide dysmutase activity,as well as theconcentrations of diene conjugates and free sulphydrilgroups,H-donating ability and reducing power of theliver samples were determined.Chemiluminescentintensity of the liver was also measured.Metal ions(Al,Ca,Cu,Fe,Mg,Mn,Zn)and P and S concentrations ofthe liver were determined with an inductively coupledplasma optical emission spectrometer and Se contentwas measured by cathodic stripping voltammetry.RESULTS:Glutathione peroxidase and superoxidedysmutase activities of the liver decreased significantlyin the hyperemia group compared to those observedin the sham operated group.The level of totalantioxidant status was also significantly lower in thehyperemia group.H-donating ability,reducing powerand free sulphydril group concentration showed thesame tendency.A significant correlation(P<0.05)wasfound between the changes in non-specific antioxidantactivities.This pointed to simultaneous activity of the antioxidant defence system.AI,Cu,Mn,Zn,and S werelower in the hyperemia group than in the sham operatedgroup when the levels of Ca,Fe,Mg,Se and P ions werehigher during hyperemia.CONCLUSION:Oxidative stress is one of the mainfactors for the injury of intact liver lobes duringischaemia-reperfusion.     

Sub-lethal oxidative stress triggers the protective effects of ischemic preconditioning in the mouse liver

BACKGROUND/AIMS: While ischemic preconditioning confers significant protection against subsequent prolonged periods of ischemia, the mechanisms triggering protection remain speculative. We hypothesize that a sub-lethal oxidative stress during ischemic preconditioning induces defense mechanisms preventing subsequent lethal injury. METHODS: We used mouse models of partial and total hepatic ischemia for 75 min. Ischemic preconditioning consisted of 10-min ischemia and 15-min reperfusion prior to the prolonged ischemic insult. RESULTS: Tissue levels of peroxides increased about three times after 10 min of ischemia and normalized within 15 min of reperfusion. This limited oxidative stress during ischemic preconditioning prevented the negative effects of subsequent prolonged ischemia as assessed by AST-levels, TUNEL-staining of hepatocytes and animal survival. N-Acetylcysteine inhibited the mild oxidative burst of ischemic preconditioning, and fully reversed the protective effects of preconditioning. The protective role of a sub-lethal oxidative stress was supported by the benefit of delivery of an H2O2-analog through the portal vein prior to a long ischemic insult. This challenge conferred similar protection as ischemic preconditioning. CONCLUSIONS: We conclude that the mild burst of oxidative stress generated during ischemic preconditioning triggers protective mechanisms against subsequent, otherwise lethal, ischemic injury. The pathway possibly includes enhancement of natural anti-oxidative stress mechanisms.     

TX小鼠铜代谢和肝损害的实验研究

目的 明确肝病模型鼠--TX小鼠的生理特点,为以其为模型的研究提供选择适合月龄动物的理论依据和自然生理情况下的对照值.方法 选取7～12个月TX小鼠和同系DL小鼠,每个月龄雌雄各3只,测定肝、脑、肾和血清中的金属铜含量,测定血清铜蓝蛋白及AST等指标,HE染色观察组织病理学改变,电镜下观察超微结构.应用SPSS13.0软件进行统计分析,组间比较采用两组完全随机化设计资料均数的t检验.结果 10、11个月龄时AST含量,TX小鼠的分别为(218.3±21.5)U/L和(197.5±38.3)U/L,DL小鼠分别为(171.5±24.1)U/L和(165.0±25.8)U/L,两组小鼠AST含量比较,t值分别为3.335和1.689,P值均＜0.05,差异有统计学意义.其他月龄小鼠AST含量,两组差异无统计学意义.肝、脑、肾的脏器每千克组织铜含量,TX小鼠平均值分别为(750.0±85.5)mg、(39.7±2.2)mg和(29.8±5.0)mg,DL小鼠平均值分别为(11.6±1.5)mg,(16.8±0.9)mg和(14.2±1.0)mg,TX小鼠肝、脑、肾脏器的铜含量均高于DL小鼠,t值分别为21.16,23.60,7.47,P值均＜0.05,差异有统计学意义.结论 TX小鼠可作为一个理想的肝损害动物模型,针对实验目的 不同应选择相应月龄的TX小鼠,TX小鼠存在自我恢复的趋势,以其为模型的研究应设立生理情况对照组,以便更好地比较出治疗处理的效果.     

补中益气丸对早期糖尿病大鼠肝氧化损害及肝糖原作用的机制

目的:研究补中益气丸对STZ糖尿病大鼠肝脏NO3-、ONOO-、MDA、糖原及肝损害的影响及机制.方法:通过2次腹腔注射链脲佐菌素(STZ)制作大鼠糖尿病模型,第1次腹腔注射STZ55mg/kg,第8天行第2次腹腔注射同等剂量STZ.每周大鼠尾尖采血测空腹血糖值,造模成功的SD大鼠随机分为糖尿病组,常规喂养4wk;补中益气丸组给予补中益气丸水溶液,每只大鼠用量为8g/kg,每天1次,连续28d.采用分光光度法测定鼠肝脏ONOO-、MDA、糖原,通过HE染色病理检查和积分系统估计肝损害程度.结果:糖尿病大鼠出现明显的糖尿病症状,肝病理检测发现肝细胞变小,肝窦变窄,肝细胞核变小浅染,肝小叶结构不清,肝索结构紊乱存在充血和少量炎性细胞浸润,尤其在肝1区肝组织MDA、ONOO-水平显著升高,肝糖原显著降低.补中益气丸组大鼠肝细胞、肝细胞核、肝窦、肝索、肝小叶异常及充血和炎症明显改善,糖尿病症状亦明显改善;肝组织MDA、ONOO-水平显著降低,肝糖原显著升高.相关分析发现,肝糖原与MDA、ONOO-、肝细胞索结构紊乱、充血、炎症呈显著负相关,与肝细胞大小、肝细胞核大小、肝血窦大小呈显著正相关;肝组织MDA、ONOO-水平与肝细胞大小、肝细胞核大小、肝血窦大小呈显著负相关,与肝细胞索结构紊乱、充血、炎症呈显著正相关.结论:补中益气丸可能通过改善STZ糖尿病大鼠肝脏氧化应激,改善胰岛素信号通路、激活磷酸酶脱磷酸化活性,进而升高糖原合成酶活性和肝糖原含量,改善肝氧化代谢和肝的氧化损伤.     

D-半乳糖胺/脂多糖所致小鼠急性肝衰竭模型正交试验优化研究

目的 通过正交试验优化D-氨基半乳糖(D-GalN)和脂多糖(LPS)致急性肝衰竭模型,确定合理造模剂量,以期使造模更加符合研究需要.方法 选取3个可能影响造模成功率的指标为实验因素:D-GalN剂量、LPS剂量、稀释倍数,每个实验因素选取4个水平,利用L16 (45)正交表安排试验,以小鼠24 h病死率为考察指标.观察小鼠血清ALT、肝组织学改变,肝脏细胞凋亡情况以验证造模效果.结果 优化后理想造模给药方案为D-GalN 350 mg/kg联合LPS 30 μg/kg,混合后稀释3倍,腹腔注射.造模后6h可出现典型肝衰竭表现.结论 优化了D-GalN/LPS致小鼠ALF模型,使其更符合科研需要.     

The role of oxidative stress in NASH and fatty liver model.

The aim of this study was to investigate whether oxidative stress is related to the development of liver injury and an iron chelator, deferoxamine (DFO) can prevent lipid peroxidation resulting in reduced liver injury as well as reduce preneoplastic lesions induced by a choline-deficient l-amino acid-defined (CDAA) diet. CDAA diet administration resulted in an increased serum ALT level after one week. Hepatocytes in rat liver fed a CDAA diet showed malondialdehyde (MDA) accumulation. But simultaneous DFO treatment for one week reduced this elevation of ALT as well as MDA accumulation in the liver. Feeding rats a CDAA diet for 14 weeks led to the development of severe liver fibrosis and preneoplastic lesions detected as enzyme-altered lesions. DFO treatment also prevented the expression of activated stellate cells, resulting in the reduction of liver fibrosis as well as reducing the development of preneoplastic lesions. These results indicate that iron chelation can reduce the development of preneoplastic lesions in a CDAA diet model.     

Chronic training increases blood oxidative damage but promotes health in elderly men

The objective of the present study was to investigate a large panel of oxidative stress biomarkers in long-term trained elderly men to analyse the effects of chronic training on an aged population. We collected blood samples from two groups of male volunteers older than 65 years who maintain a measure of functional independence: one group of sedentary subjects without a history of regular physical activity and the other of subjects who have sustained training, starting during middle age (mean training time = 49 ± 8 years). We studied morbidity and polypharmacy, as well as haematological parameters including red cell count, haemoglobin concentration, haematocrit, mean corpuscular volume, red cell distribution width and several oxidative biomarkers including protein carbonyl content and lipid peroxidation in plasma and erythrocytes, red blood cell H₂O₂-induced haemolysis test, plasma total antioxidant activity and the main antioxidant enzymes of erythrocytes: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase. After adjusting for confounding factors, we observed an increase in all oxidative damage biomarkers in the plasma and erythrocytes of the long-term exercise group. However, we reported a decrease in the number of diseases per subject with statistical differences nearly significant (p = 0.061), reduced intake of medications per subject and lower levels of red cell distribution width in the chronic exercise group. These results indicate that chronic exercise from middle age to old age increases oxidative damage; however, chronic exercise appears to be an effective strategy to attenuate the age-related decline in the elderly.     

Dissociation between functional senescence and oxidative stress resistance in Drosophila

Many studies strongly suggest a causal link between oxidative stress and determination of life span. The relationship between oxidative stress and age-related functional declines, however, is less clear. Additionally, the full spectrum of functional declines associated with aging has not been systematically evaluated in the fruit fly, Drosophila melanogaster, one of the leading models for aging research. Toward a more comprehensive assessment of functional senescence in Drosophila, we evaluated a series of behaviors in control flies of increasing ages. Our studies reveal a novel age-dependent functional decline in the olfactory system and confirm previous reports of age-related locomotor defects in flies. Behavioral responses to electric shock and light are maintained in aged flies. Thus, some sensory systems senesce during the first several weeks of life while others do not. Interestingly, the age-dependent functional declines in olfactory and locomotor systems are indistinguishable in control flies and methuselah, a mutant with enhanced resistance to oxidative stress and increased life span. Our results indicate that enhanced resistance to oxidative stress and extension of life span do not necessarily confer protection from age-related functional declines.     

Effect of the antioxidant action of Ginkgo biloba extract (EGb 761) on aging and oxidative stress

Aging is responsible for oxidative damage to DNA, protein, lipid, and other macromolecules linked to tissue alterations. The resultant damage contributes significantly to degenerative diseases, to include those of the brain, sensorial tissues, and cardiovascular system. To protect cellular components from oxyradical attack, especially lipoperoxidation, a substantial interest in the use of antioxidants has evolved. A free radical scavenger, Ginkgo biloba extract (EGb 761) may be effective in fighting the oxidative stress related to aging. Many data support the efficacy of EGb 761 in biological model systems. In aging processes, EGb 761 may ameliorate the mitochondria respiratory chain function by quenching the superoxide anion, and the hydroxyl and peroxyl radicals. It protects the brain by facilitating the uptake of neurotransmitters and by reducing ischemia-reperfusion episodes and level of apoptosis. Moreover, in sensorial tissues, EGb 761 reduces apoptosis in the olfactive bulb and in the retinal pigmented epithelium of the eye, and protects against the lipoperoxidation alteration of the retina that results in a decrease of the electroretinogram response. In the cardiovascular system, by a direct effect on oxidative low density lipoproteins, EGb 761 may decrease atherosclerosis evolution, and is shown to accelerate cardiac mechanical recovery after ischemia-reperfusion. In conclusion, the antioxidant effects of EGb 761 noted in many experimental data, may explain the therapeutic efficacy observed in clinical trials of the elderly. These beneficial properties seem in part to come from the activity of EGb 761 constituents, such as flavonoids and terpens.