Shikonin ameliorates D-galactose-induced oxidative stress and cognitive impairment in mice via the MAPK and nuclear factor-κB signaling pathway

Oxidative stress acts as the major causative factor for various age‐associated neurodegenerative diseases, triggering cognitive and memory impairments. In the present study, the underlying neuroprotective mechanism governing how shikonin acts against D-galactose (D-gal)-induced memory impairment, neuroinflammation and neuron damage was examined. The results revealed that chronic administration of D-gal [150 mg/kg intraperitoneally (i.p.)] in mice caused cognitive and memory impairments, as determined by Morris water-maze test. Shikonin treatment, however, alleviated D‐gal-induced memory impairment and reversed the D‐gal-induced neural damage and apoptosis. Furthermore, western blotting and the results of morphological analysis revealed that shikonin treatments markedly reduced D‐gal induced neuroinflammation through inhibition of astrocytosis as determined by glial fibrillary acidic protein (GFAP) detection, and downregulating other inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6. Moreover, shikonin treatment led to inhibition of the activation of nuclear factor‐κB (NF‐κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs), preventing neurodegeneration. Hence, taken together, the results of the present study suggested that shikonin attenuated D‐gal-induced memory impairment, neuroinflammation and neurodegeneration, possibly via the NF‐κB/mitogen-activated protein kinase (MAPK) pathway. Our data suggest that shikonin could be a promising, endogenous and compatible antioxidant candidate for age‐associated neurodegenerative diseases, including Alzheimer's disease.     

Evaluation of oxidative stress induction in rats following exposure to silver nanorods

The study investigated the oxidative stress induction by the 10 and 25?nm silver nanorods (SNRs) following intra-tracheal instillation in rats after 1?day, 1 week, 1 month and 3 months post instillation periods at 1 and 5?mg/kg b.w. doses. The blood was withdrawn by retro orbital plexus method after exposure periods and different oxidative stress markers were estimated. The results showed that the both sizes of SNRs induced increased levels of malondialdehyde (MDA) and depleted glutathione (GSH) levels after 1?day and 1 week post exposure periods. The 10 and 25?nm SNRs at both doses displayed that significantly reduced levels of superoxide dismutase (SOD) and catalase following 1?day and 1 week post exposure periods. Also, the results have shown that decrease in total antioxidant capacity (TAC) of both sizes of SNRs significantly following 1?day and 1 week post exposure periods, indicating the oxidative stress induction by SNRs. In spite, there were no significant changes in oxidative stress markers following 1 month and 3 months post exposure periods may be due to recovery. The increased levels of MDA and decreased levels of GSH, SOD, catalase and TAC activity are strongly associated to ROS production and lipid peroxidation, suggesting the induction of oxidative stress in rats. The 10?nm SNRs at 5?mg/kg b.w. dose exposures in rats have shown greater changes in all oxidative stress parameters, indicating the greater induction of oxidative stress when compared with the 25?nm SNRs, representing the size–dose-dependent induction of oxidative stress of SNRs.     

成人起病散发性下运动神经元病基因检测的相关研究

目的探讨成人散发起病的下运动神经元病(lower motor neuron disease,LMND)患者铜锌超氧化物歧化酶1(superoxide dismutase 1,SOD1)基因、运动神经元存活基因(survive motor neuron,SMN)及雄激素受体(androgen receptor,AR)基因对明确诊断疾病类型的作用。方法收集43例成人散发起病表现为LMND的患者取外周血提取基因组DNA,分别进行聚合酶链式反应(PCR)扩增SOD1基因外显子1-5,SMN基因外显子7及男性LMND患者AR基因外显子1,对产物进行高分辨熔解曲线分析、变性聚丙烯酰胺凝胶电泳分析及测序。结果在43例成年LMND患者中,未发现SOD1基因突变。2例男性患者有SMN1外显子7的纯合缺失,诊断为Ⅲ、Ⅳ型脊髓性肌萎缩(SMA)。在31例男性患者中发现3例AR基因外显子1的CAG三核苷酸重复序列数分别为49、50、52,可诊断肯尼迪病。结论对LMND患者进行SMN1基因外显子7及AR基因外显子1检测,可使部分散发或无明确家族史的患者明确诊断,并可对病情及预后进行评估。     

Blood-Brain Barrier Permeability of Asiaticoside,Madecassoside and Asiatic Acid in Porcine Brain Endothelial Cell Model

Neurotherapeutic potentials of Centella asiatica and its reputation to boost memory, prevent cognitive deficits and improve brain functions are widely acknowledged. The plant's bioactive compounds, i.e. asiaticoside, madecassoside and asiatic acid were reported to have central nervous system (CNS) actions, particularly in protecting the brain against neurodegenerative disorders. Hence, it is important for these compounds to cross the blood-brain barrier (BBB) to be clinically effective therapeutics. This study aimed to explore the capability of asiaticoside, madecassoside and asiatic acid to cross the BBB using in vitro BBB model from primary porcine brain endothelial cells (PBECs). Our findings showed that asiaticoside, madecassoside and asiatic acid are highly BBB permeable with apparent permeability (P_app) of 70.61 ± 6.60, 53.31 ± 12.55 and 50.94 ± 10.91 × 10^?6 cm/s respectively. No evidence of cytotoxicity and tight junction disruption of the PBECs were observed in the presence of these compounds. Asiatic acid showed cytoprotective effect towards the PBECs against oxidative stress. This study reported for the first time that Centella asiatica compounds demonstrated high capability to cross the BBB, comparable to central nervous system drugs, and therefore warrant further development as therapeutics for the treatment of neurodegenerative diseases.     

LATEX HYPERSENSITIVITY: PERSONAL DATA AND REVIEW OF THE LITERATURE

ABSTRACT

Latex allergy is an increasingly common condition, because use of latex products is widespread. The reactions to latex manufactures can be classified as allergic and non-allergic, these are the most common. Latex proteins are responsible for immediate IgE-mediated hypersensitivity allergic reactions. Symptoms range from rhinitis, conjunctivitis and urticaria to anaphylactic shock. Chemical additives can cause allergic contact dermatitis. The clinical symptoms of latex allergy could arise from direct contact with latex products, but may also result from inhalation of airborne allergens. Subpopulations at particular risk include: atopics, children with spina bifida or individuals who required frequent surgical instrumentations, health care workers, and all persons who have regular contact with latex products. Diagnosis of allergy is based initially on history; search for specific serum IgE, skin prick test and provocation test may confirm the suspicion. The most effective strategy in the treatment of latex allergy is avoidance, however this is virtually impossible, given large number of latex products we encounter since childhood. In this paper we review the current state of knowledge concerning latex allergy, including the clinical spectrum, identified allergens, the cross-reactions regarding the latex-fruit syndrome, diagnostic procedures and preventive measures. Several personal data increase awareness on this issue.     

Evaluation of p-cymene,a natural antioxidant

Abstract

Context: Several studies have demonstrated that essential oils and their major components have antioxidant activity. p-Cymene is a monoterpene and a major constituent of essential oils of various species of plants.

Objective: This paper evaluated the antioxidant potential of p-cymene in the hippocampus of mice by determining the levels of thiobarbituric acid reactive substances (TBARS), nitrite content, and activity of catalase (CAT) and superoxide dismutase (SOD).

Materials and methods: Swiss mice were intraperitoneally treated with 0.05% Tween 80 dissolved in 0.9% saline solution, ascorbic acid 250?mg/kg, and p-cymene at doses of 50, 100, and 150?mg/kg, respectively. After treatment, all groups were observed for 24?h, afterwards, the groups were euthanized for removal of the brain and dissection of the hippocampus.

Results: The results of treatment with p-cymene were a significant decrease in lipid peroxidation and nitrite content at a dose of CYM 50: 65.54%, CYM 100: 73.29%, CYM 150: 89.83%, and CYM 50: 71.21%; CYM 100: 68.61% and CYM 150:67%, respectively, when compared with the control group. The results showed that at all tested doses, p-cymene produces an increase in SOD and catalase activity significantly at a dose of CYM 50: 22.7%, CYM 100: 33.9%, CYM 150: 63.1%, and CYM 50: 119.25%, CYM 100: 151.83% and CYM 150: 182.70%, respectively, when compared with the vehicle-treated group.

Discussion and conclusion: The result of this study shows that p-cymene has an antioxidant potential in vivo and may act as a neuroprotective agent in the brain. This compound may present a new strategy in the development of treatment for many diseases in which oxidative stress plays an important pathophysiological role.     

硫氧还蛋白对大鼠睾丸缺血再灌注损伤保护作用的研究

目的 探讨硫氧还蛋白对大鼠睾丸缺血再灌注损伤的保护作用.方法 选取雄性SD大鼠60只,随机分为4组:假手术对照组(A组);睾丸扭转/复位组(B组);睾丸扭转/复位+腹腔内注射生理盐水组(C组);睾丸扭转/复位+腹腔内注射硫氧还蛋白组(D组).无菌条件下制作左侧睾丸扭转模型,扭转持续4h,复位4h后取睾丸标本(D组在复位前15 min腹腔内注射硫氧还蛋白).对标本进行病理组织学检查;检测睾丸组织中超氧化物歧化酶(SOD)和丙二醛(MDA)的含量.结果 睾丸扭转/复位后可见生精小管退变,间质出现水肿及出血,腹腔注射硫氧还蛋白使睾丸扭转/复位诱发的组织学改变明显改善.B组及C组睾丸损伤评分(8.3±0.96;8±0.87)明显高于A组(0.78±0.36)(P＜0.01),而腹腔注射硫氧还蛋白可以使睾丸损伤分值(3.1±0.42)显著降低(P＜0.05).B组及C组MDA含量(4.39±0.21;4.42±0.17)升高,SOD活性(269±27.1;271±21.3)降低,与对照组(MDA:1.61±0.18;SOD:317±22.3)相比,差别具有显著性意义(P＜0.01).而腹腔注射硫氧还蛋白能有效降低MDA含量(2.03±0.03)并升高SOD活性(315±24.2)(P＜0.01).结论 本实验为硫氧还蛋白作为治疗睾丸扭转继发损害的有效物质提供了组织学及生化依据.为临床预防和治疗睾丸缺血再灌注损伤提供了理论依据.     

极低频高压脉冲电场对萌发绿豆干旱伤害的缓解作用

采用峰值场强为100 kV·m^-1、脉宽80 ms、脉冲频率为1 Hz的极低频高压脉冲电场（ELF-PEF）处理-0.1 MPa的PEG-6000溶液中萌发的绿豆种子，研究了绿豆在萌发过程中鲜重、自发发光、延迟发光、丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性的变化。结果表明，ELF-PEF对PEG胁迫下萌发的绿豆鲜重、自发发光和延迟发光积分强度促进作用分别达到了28.58%、78.35%和40.6%，说明ELF-PEF可以有效促进绿豆种子萌发过程中的生理代谢，缓解干旱胁迫对细胞的伤害作用。ELF-PEF通过提高PEG胁迫下萌发绿豆中SOD活性，降低MDA含量，缓解干旱胁迫对萌发绿豆的氧化损伤，ELF-PEF对细胞毛细吸水和代谢吸水的促进可能是其缓解干旱伤害的原因。     

Partial characterization of superoxide dismutase activity in the Barber pole worm-Haemonchus contortus infecting Capra hircus and abomasal tissue extracts

ObjectiveTo determine the activity of superoxide dismutase (SOD) in the male and female haematophagous caprine worms, Haemonchus contortus infecting Capra hircus, and their E/S products and also to analyse the effect of Haemonchus infection on the level of host SOD.MethodsThe SOD activity was analysed by using the pyrogallol autoxidation assay and non-denaturing polyacrylamide gel electrophoresis followed by specific enzyme staining by riboflavin-nitroblue tetrazolium method.ResultsThe adult females were found to have higher enzyme activity than the male worms. Appreciable amount of SOD activity was also detected in the worm culture medium and female worms secreted more SOD in comparison to the male parasites. The SOD activity was negatively correlated to the worm burden. Statistically significant decrease in SOD activity (P<0.05) was observed in the heavily infected host tissue in comparison to the control non-infected host tissue. SOD profile of the crude extracts of both the sexes revealed polymorphism and a fast migrating activity band being characteristic of E/S products. The SOD activities were found highly sensitive to potassium cyanide indicating the Cu/Zn form of SOD.ConclusionsHaemonchus contortus is a key model parasite for drug and vaccine discovery. The presences of SOD activity in appreciable amount in the parasite as well as its E/S products indicate that it has a well-developed active antioxidant system to protect itself from the host immune attack. SOD could be the target for vaccine development which is the need of the hour as mass drug administration for parasite control has resulted in anthelmintic resistance across the globe and threatens the viability of sheep and goat industry in many regions of the world. The infection with Haemonchus causes a drastic reduction in SOD activity of the host tissue thus effecting its protective potential. One characteristic SOD band was found in the females which was not present in any other preparations and thus could be exploited for further studies on diagnostic/control measures.