白藜芦醇抑制人牙龈成纤维细胞炎症和氧化应激的机制研究

目的 探讨白藜芦醇（RSV）对牙龈卟啉单胞菌脂多糖（LPS）诱导的人牙龈成纤维细胞（HGF）的炎症和氧 化应激的调节作用。方法 原代培养HGF,将细胞分为实验1和实验2：实验1细胞分为对照组、LPS组、RSV 20 μmol/L 组、RSV 40 μmol/L组、RSV 80 μmol/L组、LPS+RSV 20 μmol/L组、LPS+RSV 40 μmol/L组和LPS+RSV 80 μmol/L组;实 验2细胞分为对照组、LPS组、LPS+RSV 40 μmol/L 组、LPS+RSV 40 μmol/L+E5564组和LPS+E5564组。通过CCK-8 法评估细胞活力。利用酶联免疫吸附试验测定白细胞介素（IL）-1β、IL-6、IL-8、肿瘤坏死因子（TNF）-α、超氧化物歧 化酶（SOD）、丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH-Px）水平。通过Western blot分析测量蛋白的表达水平。结 果 20、40和80 μmol/L RSV对HGF均没有明显的细胞毒性作用。在LPS诱导的HGF细胞中,40和80 μmol/L RSV 通过下调IL-1β、IL-6、IL-8和TNF-α的表达减弱炎症反应,降低了MDA的含量,并显著提高了SOD的水平,80 μmol/L RSV显著提高了GSH-Px水平（P＜0.05）。此外,20、40和80 μmol/L RSV可诱导Toll样受体4（TLR4）/MyD88/NF-κB 信号通路的失活,其均可降低TLR4、MyD88和p-p65蛋白的表达水平（P＜0.05）。TLR4抑制剂（E5564）通过下调IL- 1β、IL-6、IL-8和TNF-α的产生以及上调GSH-Px水平进一步增强了RSV对炎症和氧化应激损伤的缓解作用（P＜ 0.05）。结论 RSV可通过诱导TLR4/MyD88/NF-κB信号通路失活,减轻LPS导致的HGF炎症和氧化应激损伤。     

Lysergic acid diethylamide causes photoreceptor cell damage through inducing inflammatory response and oxidative stress

Lysergic acid diethylamide (LSD), a classical hallucinogen, was used as a popular and notorious substance of abuse in various parts of the world. Its abuse could result in long-lasting abnormalities in retina and little is known about the exact mechanism. This study was to investigate the effect of LSD on macrophage activation state at non-toxic concentration and its resultant toxicity to photoreceptor cells. Results showed that cytotoxicity was caused by LSD on 661?W cells after co-culturing with RAW264.7 cells. Treatment with LSD-induced RAW264.7 cells to the M1 phenotype, releasing more pro-inflammatory cytokines, and increasing the M1-related gene expression. Moreover, after co-culturing with RAW264.7 cells, significant oxidative stress in 661?W cells treated with LSD was observed, by increasing the level of malondialdehyde (MDA) and reactive oxygen species (ROS), and decreasing the level of glutathione (GSH) and the activity of superoxide dismutase (SOD). Our study demonstrated that LSD caused photoreceptor cell damage by inducing inflammatory response and resultant oxidative stress, providing the scientific rationale for the toxicity of LSD to retina.     

Hydrogen attenuates radiation-induced intestinal damage by reducing oxidative stress and inflammatory response

The small intestine is known to be particularly sensitive to radiation, and the major limiting factor of radiotherapy is the gastrointestinal syndrome that subsequently develops after its administration. The detrimental effects of radiation are mostly mediated via the overproduction of reactive oxygen species (ROS), especially the hydroxyl radical (·OH). Because hydrogen is a selective ·OH scavenger, we hypothesized that hydrogen might exert a protective effect against radiation-induced intestinal damage. Herein, radiation models were built both in mice and in an intestinal crypt epithelial cell (IEC-6) line. In the animal experiment, we demonstrated that hydrogen-rich saline significantly reduced radiation-induced intestinal mucosal damage, improved intestinal function, and increased the survival rate. In addition, radiation-induced oxidative stress damage and systemic inflammatory response were also mitigated by hydrogen treatment. Moreover, hydrogen treatment decreased cell apoptosis and maintained intestinal epithelial cell proliferation in mice. In vitro experiments using the IEC-6 cell line showed that hydrogen-rich medium significantly inhibited ROS formation, maintained cell viability, and inhibited cell apoptosis. Importantly, hydrogen treatment prevented mitochondrial depolarization, cytochrome c release, and activity of caspase-3, caspase-9, and PARP. Moreover, the decreased expression of Bcl-xl and Bcl-2 and the increased expression of Bax protein were also blocked by hydrogen treatment. In conclusion, our study concurrently demonstrated that hydrogen provides an obviously protective effect on radiation-induced intestinal and cell injuries. Our work demonstrated that this protective effect might be due to the blockage of the mitochondrial apoptotic pathway.     

二十碳五烯酸对高糖与去甲肾上腺素诱导的心肌细胞肥大的抑制作用

糖尿病性心肌肥大是糖尿病的严重并发症之一,如何改善糖尿病性左室肥大已经成为目前治疗糖尿病的重点研究课题.二十碳五烯酸(eicosapentaenoic acid,EPA)是人体必需脂肪酸之一,属于Ω-3系列多不饱和脂肪酸,其对高血压、心肌梗死等疾病的预防与治疗具有较好的效果[1],最新研究显示[2],EPA能够参与抑制转化生长因子β1(TGF-β1)和c-jun氨基末端激酶(JNK)等因子来产生抑制心肌细胞肥大的作用,那么是否EPA在糖尿病心肌病所产生的心肌细胞肥大也有同样的抑制作用,目前还未见国内外有相关报道.     

Treatment with dehydroepiandrosterone prevents oxidative stress induced by 3-nitropropionic acid in synaptosomes

This study evaluates the antioxidative effect of dehydroepiandrosterone (DHEA) treatment on 3-nitropropionic acid (3-NPA)-induced oxidative stress in striatal and brain cortex synaptosomes. The oxidative derangement was confirmed by a high level of lipid peroxidation products and protein carbonyls, as well as by an enhanced superoxide dismutase activity (p < 0.001). These changes were partially prevented by DHEA. Moreover, 3-NPA induced a drop in succinate dehydrogenase activity, while DHEA treatment restored the succinate dehydrogenase activity. These results show that DHEA reduces oxidative stress in synaptosomes isolated from the brain of 3-NPA-treated rats, and they suggest this neurosteroid may protect mitochondrial and maintain synaptic integrity against damage induced by this acid.     

Hydroxyethyl starch 130/0.4 prevents the early pulmonary inflammatory response and oxidative stress after hemorrhagic shock and resuscitation in rats

BackgroundThis study was designed to determine the effects of various resuscitation fluids on pulmonary capillary leakage and pulmonary edema after HS and fluid resuscitation (HS/R) and to determine whether an antiinflammatory or antioxidative mechanism was involved.MethodsWe induced HS by bleeding male Sprague–Dawley rats to a blood pressure of 30 to 40 mm Hg for 60 min. 60 min later, the rats were killed (HS group) or immediately resuscitated with L-isomer lactated Ringer's solution (HS + LR group), shed blood (HS + BL group), or hydroxyethyl starch (HS + HES group) to maintain the blood pressure to the original value during the 60-min resuscitation period. 3 h after resuscitation, pulmonary capillary leakage and wet/dry weight ratio, levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, malondialdehyde (MDA), oxidized and reduced glutathione (GSH and GSSG), myeloperoxidase (MPO) activity, nuclear factor (NF)-κB, activator protein (AP)-1 activation, and lung microscopic and ultrastructural histological changes were measured.ResultsHES and BL treatment significantly improved pulmonary capillary leakage, wet/dry weight ratio and lung injuries after HS/R. In addition, both HES and BL could attenuate the increase in TNF-α, IL-6, MPO levels and NF-κB activation. However, HES but not BL could attenuate the increase in MDA level and GSSH/GSH ratio and AP-1 activation.ConclusionsHES might attenuate pulmonary injuries by modulating pulmonary inflammatory response and oxidative stress, whereas BL attenuates pulmonary injuries by modulating pulmonary inflammatory response but not oxidative stress.     

Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer. High doses of cisplatin have also been known to produce hepatotoxicity, and several studies suggest that supplemental antioxidants can reduce cisplatin-induced hepatotoxicity. The present study was designed to determine the effects on the liver and heart oxidant/antioxidant system and the possible protective effects of ellagic acid on liver and heart toxicity induced by cisplatin. The control group received 0.9% saline; animals in the ellagic acid group received only ellagic acid (10 mg/kg); animals in the cisplatin group received only cisplatin (7 mg/kg); animals in cisplatin + ellagic acid group received ellagic acid for 10 days after cisplatin. The rats were killed at the end of the treatment period. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione-peroxidase (GSH-Px) and catalase (CAT) activities were determined in liver and heart tissue. While administration of cisplatin increased the MDA levels in liver and heart tissues, it decreased the GSH, GSH-Px and CAT in these samples when compared to the control group. The administration of ellagic acid to cisplatin-treated rats decreased the MDA levels, and increased GSH, GSH-Px and CAT in these samples. Cisplatin caused marked damages in the histopathological status of liver and heart tissues. These damages were ameliorated by ellagic acid administration. In conclusion, ellagic acid may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters.     

Quercetin abrogates bisphenol A induced altered neurobehavioral response and oxidative stress in zebrafish by modulating brain antioxidant defence system

Bisphenol A (BPA), a well-recognized anthropogenic xenoestrogen, has been identified as a causative agent responsible for inducing carcinogenicity, cognitive impairment, neurotoxicity, oxidative stress, etc. However, BPA-induced neurotoxicity and its possible amelioration through natural compound intervention remain elusive. The current study was performed to elucidate the neurotoxic potential of BPA in zebrafish (Danio rerio) by waterborne exposure and its possible amelioration by quercetin co-supplementation. Protective effect of quercetin against BPA-induced altered neurobehavioral response, oxidative stress and neuromorphological changes were evaluated in zebrafish brain. The present findings reveal that BPA-induced altered neurobehavioral response was ameliorated by quercetin. Biochemical studies advocate the potential therapeutic efficacy of quercetin against BPA-induced oxidative stress in zebrafish brain. Quercetin also shows neuroprotection against BPA-induced augmented neuronal pyknosis in periventricular grey zone (PGZ) of zebrafish brain. These basic findings indicate that quercetin may act as an effective intervention against BPA-induced neurotoxicity in zebrafish through down-regulation of oxidative stress.     

Succinic acid monoethyl ester prevents oxidative stress in streptozotocin-nicotinamide-induced type2 diabetic rats

Succinic acid mono ethyl ester (EMS) was recently proposed as an insulinotropic tool in the treatment of non-insulin dependent diabetes mellitus. The aim of this study was to investigate the effect of EMS on oxidative stress in a streptozotocin (STZ)-nicotinamide induced type 2 diabetic model. The EMS was injected intraperitoneally at 8 micro mol/g body weight for 30 days. Plasma glucose, plasma insulin, thiobarbituricacid reactive substances (TBARS), hydroperoxides, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), reduced glutathione (GSH), glutathione-S-transferase (GST), and vitamins C and E were assayed in liver and kidney. Treatment with EMS and metformin to diabetic rats resulted in a significant reduction in plasma glucose, TBARS, and hydroperoxides. In addition, the treated groups also showed a significant increase in the activities of plasma insulin, SOD, CAT, GPx, GST, GSH, vitamin C, and vitamin E in liver and kidney of STZ-nicotinamide-induced diabetic rats. Our result suggest that non glucidic nutrient, such as EMS as a potent antidiabetic, may optimalize antiperoxidative and antioxidants status by restoring the biochemical alterations found in STZ-nicotinamide-induced type 2 diabetes.     

隐丹参酮对慢性不可预见应激联合脂多糖所致抑郁小鼠氧化应激和炎症反应的影响

目的 观察隐丹参酮对慢性不可预见应激（CUMS）联合脂多糖（LPS）所致抑郁小鼠氧化应激和炎症反应的影响。方法 60只清洁级ICR小鼠随机分为对照组、模型组、帕罗西汀组（20 mg/kg）及隐丹参酮低、中、高剂量（10、20、40 mg/kg）组,每组10只。采用CUMS＋LPS应激刺激14 d建立抑郁模型（除对照组）,同时ig相应药物或生理盐水,1次/d,连续14 d。通过体质量增量、糖水偏好指数、悬尾实验及新奇环境摄食测试评价抑郁行为,并测定各组血清超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）,海马和皮质白细胞介素（IL）-6、IL-1β、肿瘤坏死因子（TNF）-α变化情况。结果 隐丹参酮20、40 mg/kg组体质量增量及SOD、CAT、GSH-Px酶活性高于模型组,不动时间短于模型组（P＜0.05、0.01）,海马IL-6、海马和皮质IL-1β含量低于模型组（P＜0.05、0.01）。各治疗组糖水偏好指数高于模型组、摄食潜伏期短于模型组（P＜0.05、0.01）,血清MDA、皮质TNF-α含量低于模型组（P＜0.05、0.01）。隐丹参酮40 mg/kg组皮质IL-6、海马TNF-α含量低于模型组（P＜0.01）。结论 隐丹参酮对CUMS联合LPS致小鼠抑郁症状有改善作用,其机制可能与抑制过强的氧化应激反应与神经炎症反应,并减轻神经元损伤有关。     

内质网应激与炎症

内质网(endoplasmic reticulum,ER)应激是真核细胞的一种保护性应激反应,通过激活未折叠蛋白反应(unfoldedprotein response,UPR)来减少细胞内蛋白的异常聚集,从而起到细胞保护作用,而长期、严重的ER应激则会诱导细胞凋亡或死亡。能引起ER应激的因素很多,如基因突变或机体的状态改变包括氧化应激、缺血、营养不足、病毒感染和钙平衡失调等。近来研究发现,ER应激在机体的炎症反应中发挥重要作用,UPR与炎症反应通路之间通过多种机制相互偶联,参与多种炎症性疾病的发生发展。该文就近年来关于ER应激与炎症相关性的研究进展做一综述。     

Uric acid and oxidative stress

Uric acid is the final product of purine metabolism in humans. The final two reactions of its production catalyzing the conversion of hypoxanthine to xanthine and the latter to uric acid are catalysed by the enzyme xanthine oxidoreductase, which may attain two inter-convertible forms, namely xanthine dehydrogenase or xanthine oxidase. The latter uses molecular oxygen as electron acceptor and generates superoxide anion and other reactive oxygen products. The role of uric acid in conditions associated with oxidative stress is not entirely clear. Evidence mainly based on epidemiological studies suggests that increased serum levels of uric acid are a risk factor for cardiovascular disease where oxidative stress plays an important pathophysiological role. Also, allopurinol, a xanthine oxidoreductase inhibitor that lowers serum levels of uric acid exerts protective effects in situations associated with oxidative stress (e.g. ischaemia-reperfusion injury, cardiovascular disease). However, there is increasing experimental and clinical evidence showing that uric acid has an important role in vivo as an antioxidant. This review presents the current evidence regarding the antioxidant role of uric acid and suggests that it has an important role as an oxidative stress marker and a potential therapeutic role as an antioxidant. Further well designed clinical studies are needed to clarify the potential use of uric acid (or uric acid precursors) in diseases associated with oxidative stress.     

Gallic acid attenuates chromium-induced thyroid dysfunction by modulating antioxidant status and inflammatory cytokines

Hexavalent chromium-mediated oxidative stress causes severe organ damage. The present study was designed to investigate the possible thyroprotective effect and underlying mechanisms of gallic acid using rat model of potassium dichromate-induced thyroid dysfunction. Forty adult male albino rats were divided into 4 groups: control, gallic acid (20 mg GA/kg b. wt), potassium dichromate (2 mg PD/kg b. wt) and the fourth group was co-treated with PD and GA. PD-injection resulted in decreased serum free triiodothyonine (FT3), free thyroxine (FT4) with concomitant significant increase in thyroid stimulating hormone (TSH) levels. Superoxide dismutase (SOD), glutathione-S-transferase (GST) activities and their respective mRNA expression and reduced glutathione (GSH) content were significantly decreased. Thyroid nitrosative stress marker (NO level and iNOS mRNA and protein expression) and pro-inflammatory cytokines (serum TNF-α, IL-6 and thyroid TNF-α, IL-6 and COX-2 gene and protein expression levels) were disturbed. Histopathological changes revealed distended, collapsed and degenerated follicles with vacuolated cytoplasm. GA co-treatment attenuated pro-inflammatory cytokines, the thyroid expression of iNOS, TNF-α, IL-6 and COX-2, decreased the elevated lipid peroxidation biomarkers and NO level and up- regulated SOD and GST mRNA expression levels. In conclusion, GA has shown strong modulatory potential against PD-induced inflammation and oxidative stress in albino rats.     

Benidipine prevents oxidative stress,inflammatory changes and apoptosis related myofibril damage in isoproterenol-induced myocardial infarction in rats

Abstract

Objective: The effects of benidipine on oxidative stress and myocardial apoptosis were assessed in isoproterenol (ISO)-induced myocardial infarction (MI) in wistar rats.

Materials and method: Animals were pretreated with benidipine (1, 3, 10?μg/kg/day Body weight) intravenously for a period of 28 days. After pretreatment, ISO (85?mg/kg Body weight, subcutaneous) was injected in rats at an interval of 24?h to induce MI. Myocardial oxidative stress, cardiac biomarkers, apoptosis, inflammatory mediators, and ultrastructural architecture of the cardiac tissue were assessed in ISO-induced MI in rats.

Result: Significant variation in the level of TBA, antioxidant enzymes (GSH, CAT, SOD, GPx, GRx, GST) in myocardium, cardiac biomarkers (CK-MB, LDH) in serum, Caspase-3, C-reactive protein (CRP), and alteration in ultrastructural architecture of cardiac tissue confirmed the cardiotoxicity induced by ISO. Pretreatment with benidipine preserved the lipid peroxide and antioxidant enzymes, and furthermore showed maintained levels of myocardial biomarker, CRP and caspase-3. Ultrastructure architecture of cardiac tissue was also found to be well preserved.

Conclusion: The present study suggested cardioprotective effect of benidipine which may possibly be due to its antioxidant activity and antiapoptotic nature.     

Antioxidant response to oxidative stress induced by smoking

Oxygen free radicals have been hypothesized to play a pivotal role in the deleterious effects of smoking on health. The present study was undertaken to examine the oxidant and antioxidant system among smokers and nonsmokers. Fourteen smokers and 11 nonsmokers were enrolled for this study. The protein carbonyl levels in smokers were found to be significantly higher than in nonsmokers. The levels of plasma ascorbic acid, free sulfhydryl group, and erythrocyte reduced glutathione were lower in smokers compared to nonsmokers. In smokers the erythrocyte activities of both glutathione peroxidase and catalase were decreased when compared to that in nonsmokers. The data from the study reemphasizes the presence of oxidative stress in smokers. The concomitant decrease in the activities of both catalase and glutathione peroxidase found in the erythrocytes of smokers raises rational grounds for expressing concern over the increased susceptibility towards oxidative stress in these subjects.     

Methane-rich saline alleviates cerulein-induced acute pancreatitis by inhibiting inflammatory response,oxidative stress and pancreatic apoptosis in mice

BackgroundAcute pancreatitis (AP) is a potentially life-threatening gastrointestinal disease involving intracellular activation of digestive enzymes and pancreatic acinar cell injury. The present study was performed to investigate whether methane-rich saline (MS) was involved in the regulation of AP.MethodsMS (16 ml/kg) was administered at different dosing frequencies on mice with cerulein-induced AP. Serum amylase, lipase and histopathological changes in the pancreas tissue were measured. Serum cytokine TNFα, IL-6, IFNγ and IL-10 were detected by ELISA. The mRNA levels of these inflammatory cytokines in the pancreas were detected by real time-PCR. Myeloperoxidase (MPO) and superoxide dismutase (SOD) were determined using commercial kits. Apoptosis was assessed by immunohistochemistry and Western blot.ResultsMS treatment reversed the increased serum level of amylase and lipase, alleviated the pathological damage in the pancreas, and decreased the expression of TNFα, IL-6, IFNγ and IL-10 in cerulean-induced AP mice. In addition, MPO was down-regulated and SOD was up-regulated in the MS treated pancreas, indicating that MS had an anti-oxidant effect against AP. Furthermore, MS protected pancreatic cells against cerulean-induced apoptosis and abolished cleaved caspase-3.ConclusionMS exerted anti-inflammatory, anti-oxidant and anti-apoptotic effects on cerulein-induced AP in mice and may proved to be a promising therapeutic agent for the clinical treatment of pancreatitis.     

Catechin prevents tamoxifen-induced oxidative stress and biochemical perturbations in mice

Natural antioxidants like catechin are now known to have a modulatory role on physiological functions and biotransformation reactions involved in the detoxification process, thereby affording protection from toxic metabolic actions of xenobiotics. Reactive oxygen intermediates have been demonstrated to play an etiological role in anticancer drug-induced toxicity. This study was performed to explore the modulatory and protective effect of catechin on the toxicity of an anticancer drug, tamoxifen (TAM) with special reference to protection against disruption of glutathione metabolizing and antioxidant enzymes. TAM treatment resulted in a significant increase in the lipid peroxidation (LPO), H(2)O(2) generation and protein carbonyl (PC) contents in the liver and kidney as compared to controls while catechin+TAM-treated group showed significant decrease in LPO levels, H(2)O(2) generation and PC contents in liver and kidney when compared with TAM-treated group. Non-enzymatic antioxidants like reduced glutathione (GSH) and low molecular antioxidants like ascorbic acid (AsA) also showed normalcy due to exogenous catechin administration. Catechin pre-treatment showed restoration in the level of cytochrome P450 (CYP) content and in the activities of glutathione metabolizing enzymes, viz., glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) and other antioxidant enzymes such as, glucose-6-phosphate dehydrogenase (G6-PD), catalase (CAT) and superoxide dismutase (SOD) in both liver and kidney when compared to TAM-treated animals. The results of the study show that catechin supplementation might be helpful in abrogation of TAM toxicity during chemotherapy. Additionally, it makes it a prophylactic and preventive agent of anticancer drug-induced oxidative stress.