Supplementation with l-glutathione improves oxidative status and reduces protein nitration in myenteric neurons in the jejunum in diabetic Rattus norvegicus

Diabetes mellitus is a syndrome with multiple etiologies, characterized by chronic hyperglycemia that increases the production of reactive oxygen species and decreases antioxidant defenses. The present study evaluated oxidative stress parameters and protein nitration in myenteric neurons in the jejunum in diabetic rats supplemented with l-glutathione. Rats (90?days of age) were distributed into four groups (n?=?6/group): normoglycemic (N), normoglycemic supplemented with l-glutathione (NGT), diabetic (D), and diabetic supplemented with l-glutathione (DGT). At 210?days of age, the animals were sacrificed, and the jejunum was collected, washed, and subjected to various procedures: tert-butyl hydroperoxide chemiluminescence (CL), determination of total antioxidant capacity (TAC), determination of catalase activity, quantification of nitric oxide (NO), and double-labeling of HuC/D-immunoreactive myenteric neurons and nitrotyrosine (3-NT). Diabetes increased oxidative stress in the jejunum in the D group, reflected by increases in lipid peroxidation, TAC, catalase activity, and NO. The D group exhibited an increase in the percentage of myenteric neurons that were double-labeled with 3-NT. Supplementation with l-glutathione did not cause differences in the average CL curves between the D and DGT groups, but reductions of TAC and catalase activity were observed. Supplementation with l-glutathione promoted a reduction of neurons that contained 3-NT in the DGT group. Diabetes mellitus promoted oxidative stress in the jejunum, and supplementation with l-glutathione improved oxidative status by preventing protein nitration in myenteric neurons in diabetic animals that received supplementation.     

胆红素预防兔实验性动脉粥样硬化形成的研究

目的通过兔实验性动脉粥样硬化(atherosclerosis,AS)试验探讨体内的强抗氧化剂—血清胆红素防止AS形成的作用及机制。方法在新西兰白兔食饵性AS模型上,观察胆红素治疗性给药对氧化低密度脂蛋白(oxidized low-density lipoprotein,ox-LDL)、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)等水平变化及对主动脉壁粥样硬化斑块形成的影响。血清胆红素采用重氮法测定,ox-LDL采用ELISA法测定,TC、TG采用酶法测定,LDL-C采用Friedward公式计算。结果实验第43天,AS模型组的血清胆红素较正常对照组及胆红素处理组降低(P<0.05,P<0.01),胆红素处理组的ox- LDL较正常对照组增高但低于AS模型组(P<0.05,P<0.01),胆红素处理组与AS模型组的TC、TG、LDL-C等水平无显著差异(P>0.05)。结论胆红素在体内的浓度降低,致使体内抗氧化能力减弱,LDL-C氧化修饰形成ox-LDL增多,使细胞内大量脂质聚集形成泡沫细胞,导致AS形成。适当提高体内胆红素浓度以增加体内抗氧化能力,有利于抑制LDL-C氧化形成ox-LDL,防止泡沫细胞形成,可能是防治AS的又一重要途径。     

Comparison of the Dietary Antioxidant Profiles of 21 a priori Defined Mediterranean Diet Indexes

Background

The Mediterranean Diet (MD) is a dietary pattern that features a high quotient of antioxidant-rich foods. Differences in the level of dietary antioxidants intake reflected by different MD indexes has received little research attention.

Repletion of antioxidant status by EGCG and retardation of oxidative damage induced macromolecular anomalies in aged rats

Ageing is defined as the loss of ability to maintain cellular homeostasis of an organism associated with the free radical-elicited oxidative damage to cellular macromolecules. The aim of this study was to evaluate the efficacy of epigallocatechin-3-gallate (EGCG), the key component of green tea catechins on attenuating the age associated oxidative perturbances by assessing the redox status in mitotic (liver) and post-mitotic (skeletal muscle) tissues of young and aged rats. From the results, we observed an increase in the marker for oxidative damage such as lipid peroxidation and protein carbonyl content in aged rats, when compared to young rats. This was accompanied with decreased levels of both enzymic and non-enzymic antioxidants and redox index. On supplementation with EGCG (100 mg/kg body weight by oral gavage for 30 days), the levels of lipid peroxidation and protein carbonyl content were significantly decreased in aged rats, possibly by enhancing the GSH redox status, and both enzymic and non-enzymic antioxidants status. In conclusion, this study supports the beneficial effect of EGCG in alleviating oxidative disturbances in ageing and retard the age associated derangements in both mitotic and post-mitotic tissues.     

Neuroprotective effect of N-acetylcysteine in the development of diabetic encephalopathy in streptozotocin-induced diabetes

Diabetic encephalopathy is characterized by impaired cognitive functions that involve neuronal damage triggered by glucose driven oxidative stress. The objective of the present study was to determine whether N-acetylcysteine (NAC) supplementation ameliorates learning and memory deficits caused by hyperglycemia-induced oxidative stress in experimental diabetes. Male Wistar rats (200–250 g) were rendered diabetic by a single intraperitoneal injection of streptozotocin (50 mg/kg). Cognitive deficits were observed in diabetic animals assessed using elevated plus maze test after 8 weeks of induction of diabetes. Acetylcholinesterase activity, a marker of cholinergic function, was decreased by 15.6% in the cerebral cortex, 20.9% in cerebellum and 14.9% in brain stem of diabetic rats compared to control rats. There was an increase in lipid peroxidation in cerebral cortex (21.97%), cerebellum (20.4%) and brain stem (25.5%) of diabetic rats. This was accompanied by decrease in glutathione and total thiol content along with decrease in the activities of superoxide dismutase, catalase and glutathione reductase. However, glutathione peroxidase activity increased by 11.2%, 13.6% and 23.1% in cerebral cortex, cerebellum and brain stem respectively, while the activity of glutathione-s-transferase decreased only in cerebral cortex (21.7%). Supplementation with NAC (1.4 g/kg/day in drinking water) significantly attenuated cognitive deficits and oxidative stress in diabetic rats. Our results emphasize the involvement of increased oxidative stress in cognitive impairment in diabetic animals and point towards the potential beneficial role of NAC as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and treatment of diabetic encephalopathy.     

Neuroprotective antioxidant STAZN protects against myocardial ischemia/reperfusion injury

BACKGROUND: Protecting the myocardium from ischemia-reperfusion injury has significant potential to reduce the complications of myocardial infarction and interventional revascularization procedures. Reperfusion damage is thought to result, in part, from oxidative stress. Here we use a novel method of percutaneous coronary occlusion to show that the potent antioxidant and neuroprotective free-radical scavenger, stilbazulenyl nitrone (STAZN), confers marked cardioprotection when given immediately prior to reperfusion. METHODS AND RESULTS: Physiologically controlled male Sprague-Dawley rats were anesthetized with isoflurane, paralyzed with pancuronium and mechanically ventilated. A guide wire was introduced via the femoral artery and advanced retrogradely via the aorta into the left coronary artery under fluoroscopic guidance. Rats with established coronary ischemia (85 min after occlusion) were given STAZN 3.5 mg/kg or its vehicle 5 min before and 2 h after reperfusion, and were subjected to functional and histopathologic studies at 3 days. Ischemia-associated Q wave amplitude was reduced by 73% in STAZN-treated rats (P=0.01), while infarct-related ejection fraction, fractional shortening and severe regional wall-motion impairments were improved by 48%, 54% and 37%, respectively, relative to vehicle-treated controls (P=0.05). Total myocardial infarct volume in STAZN-treated rats was correspondingly reduced by 43% (P<0.05), representing a sparing of 14% of the total left ventricular myocardium. CONCLUSIONS: STAZN, a second-generation azulenyl nitrone with potent neuroprotective efficacy in brain ischemia, is also a rapidly acting and highly effective cardioprotective agent in acute coronary ischemia. Our results suggest the potential for clinical benefit in the setting of acute coronary syndromes.     

银杏叶总黄酮体内抗肿瘤作用及抗氧化活性研究

【目的】探讨银杏叶总黄酮体内抗肿瘤作用及抗氧化活性。【方法】选取健康的纯昆明种小鼠72只,随机分为6组,每组12只,分别为①空白对照组;②模型组;③环磷酰胺组;④低剂量黄酮组;⑤中剂量黄酮组;⑥高剂量黄酮组。利用 S180瘤细胞悬液进行实体瘤造模,比较各组平均瘤重和抑瘤率的差异,各组小鼠瘤组织中Bcl-2和Bax表达水平的差异,小鼠血清/肝脏中抗氧化相关物质含量的差异。【结果】银杏叶总黄酮具有明显的抑制瘤生长的作用,且高剂量黄酮组的平均瘤重(0.723±0.215)g 低于中剂量黄酮组(0.854±0.312)g和低剂量黄酮组(0.917±0.231)g,且差异有显著性(P <0.05);高剂量黄酮组的 Bcl-2表达低于中剂量和低剂量黄酮组,高于环磷酰胺组;高剂量黄酮组的 Bax 表达高于中剂量和低剂量黄酮组(0.152±0.023),低于环磷酰胺组,且差异均有显著性(P <0.05);高剂量黄酮组的总抗氧化能力(T-AOC)、过氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)高于中剂量和低剂量黄酮组,高剂量黄酮组的丙二醛(MDA)低于中剂量和低剂量黄酮组,且差异均有显著性(P <0.05)。【结论】银杏叶总黄酮有明显的抗肿瘤和抗氧化作用。     

纳米二氧化钛与脂多糖对小鼠肝脏抗氧化性能的影响

目的：比较慢性经口暴露不同尺寸二氧化钛(titanium dioxide, TiO2)对小鼠肝脏组织抗氧化性能的影响,并探讨纳米TiO2在小鼠肝脏中对脂多糖(lipopolysaccharide, LPS)易感性的影响。方法：将90只4 周龄清洁级雄性ICR小鼠分为18组,分别饲喂维持饲料、1%（质量分数）纳米TiO2（34 nm）饲料、1%（质量分数）亚微米TiO2（125 nm）饲料1个月、3个月、6个月,饲养结束后的第2天再分别灌胃给予0或10 mg/kg LPS,4 h后处死小鼠,记录体重及肝重,并计算肝脏系数,取肝组织制备匀浆测定抗氧化指标,包括总抗氧化能力（total antioxidant capacity,T-AOC）、总超氧化物歧化酶（total superoxide dismutase,T-SOD）、谷胱甘肽过氧化物酶（glutathione peroxidase,GSH PX）、丙二醛（malondialdehyde,MDA）。结果：小鼠的体重改变仅在染毒1个月的情况下出现,表现为各处理组的体重与对照组相比显著下降,肝脏系数在各组均未发生明显变化。染毒1个月、6个月小鼠纳米TiO2+LPS处理组、亚微米TiO2+LPS处理组与对照组、纳米TiO2处理组、亚微米TiO2处理组和LPS处理组相比,肝脏T-AOC、T-SOD、MDA三项指标有不同程度的升高。染毒3个月小鼠不同尺寸TiO2处理组的肝脏MDA活性降低。染毒1个月与6个月小鼠不同尺寸TiO2处理组下各项指标结果间差异无统计学意义,与对照组间差异也无统计学意义。结论：长期口服纳米TiO2和亚微米TiO2对成长期小鼠肝脏更容易产生损伤,且损伤既可能是还原损伤也可能是氧化损伤,小尺寸TiO2会提高小鼠肝脏对LPS的易感性,并随着暴露时间的增加而提高。     

抗氧化剂对妊娠结局的影响

目的：妊娠期妇女预防性应用抗氧化剂（维生素C,维生素E和丹参）,了解抗氧化剂对产科并发症、分娩情况和围生儿情况的影响。方法：将2005年4月—2006年7月全国24家医院3 485例妊娠妇女前瞻性随机分为抗氧化剂组［应用维生素和（或）丹参者,1 607例］与对照组（未用任何药物者,1 878例）,序贯性监测其产科并发症、分娩情况及新生儿情况。结果：①2组产科并发症比较,抗氧化剂组胎膜异常、胎儿宫内窘迫和羊水异常的发生率均低于对照组（P ＜0.01）,但2组间妊娠期糖尿病（GDM）、妊娠期高血压（PIH）和妊娠合并肝内胆汁淤积（ICP）发生率的差异无统计学意义（P ＞0.05）。②抗氧化剂组平均妊娠周为39.17周,平均新生儿体质量为3 388.29 g,对照组平均分娩时间为39.08周,新生儿体质量为3 374.81 g,2组间差异均无统计学意义（P ＞0.05）。2组间早产、低体质量儿及巨大儿的发生率差异均无统计学意义（P ＞0.05）。③抗氧化剂组孕产妇病死率为0,围生儿病死率为0.44%,对照组分别为0.11%和0.11%,2组间差异无统计学意义（P ＞0.05）。④抗氧化剂组的新生儿疾病发病率明显低于对照组（P ＜0.01）,以新生儿黄疸最为显著。结论： 妊娠期应用抗氧化剂对分娩时间、新生儿体质量、早产、低体质量儿、巨大儿、孕产妇及围生儿病死率等无明显影响,而对预防部分产科并发症和新生儿疾病等方面有所帮助,尤其预防胎膜早破、新生儿黄疸等疾病的效果肯定。