Interplay between the pro-oxidant and antioxidant systems and proinflammatory cytokine levels,in relation to iron metabolism and the erythron in depression

As there is strong evidence for inflammation and oxidative stress in depression, the aim of this study was to elucidate the relationship between oxidative imbalance and cellular immune response and to ask whether these processes are linked with iron metabolism in depressed patients. Blood was collected from patients diagnosed with recurrent depressive disorder (n=15) and from healthy controls (n=19). Whole-blood reduced glutathione (GSH), erythrocyte superoxide dismutase (SOD-1), glutathione peroxidase (GPx-1), glutathione reductase, malondialdehyde (MDA), and methemoglobin (MetHb) and plasma H₂O₂ were assayed spectrophotometrically. The serum heme oxygenase 1 (HO-1), cytokine, neopterin, and iron statuses were measured by ELISA. DNA damage was analyzed by comet assay. Serum concentrations of ferritin and soluble transferrin receptor were assayed by ELISA. MetHb saturation was analyzed spectrophotometrically in red blood cell hemolysate. The erythron variables were measured using a hematological analyzer. We observed a significant decrease in GPx-1 and SOD-1 activities and decreased levels of HO-1 and GSH in depressed patients compared to controls. Conversely, compared with controls, we found increased concentrations of MDA and H₂O₂ and more DNA damage in depressed patients. Furthermore, the levels of the proinflammatory cytokine interleukin-6 and of neopterin were increased in depressed patients along with decreased hemoglobin and hematocrit. A strong association between antioxidant defense, cytokine levels, and iron homeostasis was also revealed. These findings show that depression is associated with increased oxidative stress, inflammation, and restrictions on the available iron supply for red blood cell production. Furthermore, decreased antioxidant defense correlates with an increased cellular inflammatory response, whereas both concur with erythron and iron status, the latter explained by significant canonical correlations with the set of free radical scavenging enzymes and proinflammatory enzymes. The strong links between immune function, oxidative stress, and iron homeostasis suggest the presence of a self-sustaining multipathway mechanism that may progressively worsen, i.e., throughout accumulation of oxidative damage, producing the functional and structural consequences associated with depression. Hence, identifying viable therapeutic strategies to tackle oxidative stress and accompanying physiological disturbances, including inflammation and anemia, of chronic disease provides more opportunities for the treatment and, ultimately, prevention of depression.     

丁酸梭菌替代金霉素对肉鸡腿肌肉品质和抗氧化功能的影响

丁酸梭菌(Clostridium butyricum)是一种产丁酸等短链脂肪酸的有益菌,添加到饲料中可改善动物的生产性能、提高饲料利用率和机体的抗氧化功能.[目的]本文研究了丁酸梭菌替代金霉素添加到肉鸡日粮中,对肉鸡腿肌肉品质和抗氧化功能的影响.[方法]随机选取1日龄健康艾拔益加(AA)肉仔鸡360只,分为3组,每组8...     

The effects of percutaneous transluminal coronary intervention on biomarkers of oxidative stress in the erythrocytes of elderly male patients

Objectives: Oxidative stress plays a key role in the pathogenesis of coronary artery disease. The aim of this study was to compare the effects of percutaneous transluminal coronary angioplasty (PTCA) and elective coronary angiography (EC) on erythrocytic antioxidant defense in elderly male patients.

Methods: Twenty-three stable angina pectoris (SAP) patients undergoing PTCA and 18 patients with ischemic symptoms scheduled to undergo diagnostic EC were included in the study. The concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) and the activities of Zn,Cu-superoxide dismutase (SOD-1), catalase (CAT), and cytosolic glutathione peroxidase (GSH-Px) were examined in the erythrocytes before, immediately after and 2 weeks following PTCA or EC.

Results: The MDA concentrations were significantly higher and SOD-1, CAT, and GSH-Px activities were significantly lower in the PTCA group than in the EC group at baseline. Two weeks after treatment, the activities of the enzymes significantly increased in both groups, whereas the MDA concentrations decreased only in the PTCA patients.

Conclusions: The results confirm that an advanced state of atherosclerosis is related to greater levels of oxidative stress. The study indicates that both procedures may induce antioxidant defenses; however, PTCA exclusively induces a long-term reduction in lipid peroxidation.     

Glutathione oxidation correlates with one-lung ventilation time and PO2/FiO2 ratio during pulmonary lobectomy

Objectives: During lung lobectomy, the operated lung completely collapses with simultaneous hypoxic pulmonary vasoconstriction, followed by expansion and reperfusion. Here, we investigated glutathione oxidation and lipoperoxidation in patients undergoing lung lobectomy, during one-lung ventilation (OLV) and after resuming two-lung ventilation (TLV), and examined the relationship with OLV duration.

Methods: We performed a single-centre, observational, prospective study in 32 patients undergoing lung lobectomy. Blood samples were collected at five time-points: T0, pre-operatively; T1, during OLV, 5 minutes before resuming TLV; and T2, T3, and T4, respectively, 5, 60, and 180 minutes after resuming TLV. Samples were tested for reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione redox potential, and malondialdehyde (MDA).

Results: GSSG and MDA blood levels increased at T1, and increased further at T2. OLV duration directly correlated with marker levels at T1 and T2. Blood levels of GSH and glutathione redox potential decreased at T1?T3. GSSG, oxidized glutathione/total glutathione ratio, and MDA levels were inversely correlated with arterial blood PO₂/FiO₂ at T1 and T2.

Discussion: During lung lobectomy and OLV, glutathione oxidation, and lipoperoxidation marker blood levels increase, with further increases after resuming TLV. Oxidative stress degree was directly correlated with OLV duration, and inversely correlated with arterial blood PO₂/FiO₂.     

Mercury-induced changes in growth variables and antioxidative enzyme activities in Indian mustard

Abstract

In a hydroponic system, experiments were conducted to study the effect of different levels of mercury treatments (0, 5, 10, 25 and 50 µM Hg) on Indian mustard (Brassica juncea L. Czern & Coss.) cv. Pusa Jai Kisan. Concentration-dependent inhibitory effects were observed on growth characteristics (plant dry mass, leaf area, shoot and root length). These were accompanied by an increase in shoot Hg content and in oxidative stress characteristics such as the MDA and H₂O₂ levels. The plant growth decreased maximally at 50 µM of Hg. Despite a reduction in growth, activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) were enhanced with increase in Hg-treatments. The Hg-induced alterations in growth are linked with increase in lipid peroxidation (MDA and H₂O₂), whereas the enhancement in activities of antioxidant enzymes protects plants from Hg-induced oxidative stress.     

Lead-induced oxidative damage in rats/mice: A meta-analysis

BackgroundLead (Pb) is ubiquitous in the environment and is an environmental genotoxic metal. Pb accumulation in the body could cause the oxidative stress.ObjectiveThis meta-analysis aimed to perform a systematic evaluation of the extent of oxidative damage in rats/mice induced by lead.MethodsAll relevant articles in English or Chinese were retrieved from Embase, PubMed, Web of Science, Medline, China National Knowledge Infrastructure, and Chinese Biological Medicine databases from their inception date until July 22, 2018.ResultsA total of 108 eligible articles were included in this study. The indicators of oxidative stress included malondialdehyde (MDA), glutathione disulfide (GSSG), reactive oxygen species (ROS), hydrogen peroxide (H₂O₂), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione-s-transferase (GST). The meta-analysis showed that lead significantly increased oxidants levels, such as MDA, GSSG, ROS, and H₂O₂ (P < 0.05), and significantly reduced the level of antioxidants, such as CAT, GPx, GR, GSH, SOD, and GST (P < 0.05). The intraperitoneal mode was more effective than water drinking mode in reducing the levels of CAT, GPx, GSH, and SOD (P < 0.05). Other factors that influenced the overall oxidative stress, including species of animals, type of tissues, and intervention dosage and time, were comprehensively evaluated.ConclusionThe results of meta-analysis indicated that mice were more sensitive to lead than rats, and intraperitoneal mode was an effective intervention mean. High doses and long periods of lead treatment can cause serious oxidative damage. Moreover, testicular was more vulnerable to lead than other tissues. These results provided scientific evidence for preventing and treating lead toxicity.     

Differential response to paraquat induced oxidative stress in two rice cultivars on antioxidants and chlorophyll a fluorescence

The responses of antioxidative system and photosystem II photochemistry of rice (Oryza sativa L.) to paraquat induced oxidative stress were investigated in a chilling-tolerant cultivar Xiangnuo no. 1, and a chilling-susceptible cultivar, IR-50. Electrolyte leakage and malondialdehyde (MDA) content of Xiangnuo no. 1 were little affected by paraquat, but they increased in IR-50. After paraquat treatment, superoxide dismutase (SOD) activity remained high in Xiangnuo no. 1, while it declined in IR-50. Activities of catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR) declined with oxidative stress in both cultivars, but Xiangnuo no. 1 had higher GR activity than IR-50. Under paraquat induced oxidative stress, ascorbic acid (AsA) and reduced glutathione (GSH) concentrations remained high in Xiangnuo no. 1, but decreased in IR-50. The results indicated that higher activities of SOD and GR and higher contents of AsA and GSH in Xiangnuo no. 1 under paraquat induced oxidative stress were associated with its tolerance to paraquat, while paraquat induced damage to IR-50 was related to decreased activities of SOD, APX and GR and contents of AsA and GSH. F _v/F _m, Φ _PSII, and qP remained high in Xiangnuo no. 1, while they decreased greatly in IR-50 under paraquat induced oxidative stress.     

Properties of melanin from Lachnum YM156 and its hepatoprotective effect in Cd-exposure mice

Natural melanin was extracted from Lachnum YM156 (LIM). LIM had better thermostability and light resistance, and its solubility was relatively high under alkaline conditions. Simultaneously, we examined its hepatoprotective effect in Cd-exposure mice. Cd-exposure resulted in decreasing weight growth rate, raised liver index, elevated serum levels of alanine aminotransferase (ALT) and aspartate aminotransaminase (AST), and increased Cd accumulation in livers. Hepatic oxidative stress was evidenced by increased malondialdehyde (MDA) contents, decreased glutathione (GSH) contents, and decreased activities of dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) after CdCl₂ administration. Additionally, Cd-exposure also increased the liver level of tumor necrosis factor (TNF)-α and interleukin(IL)-1β. Furthermore, the result of quantitative real-time polymerase chain reaction(qRT-PCR) showed that Cd-exposure reduced the mRNA expression level of NF-E2-related factor 2 (Nrf2), heme oxygenase (HO-1), NADPH quinone oxidoreductase 1 (NQO-1), and elevated the mRNA expression level of factor-kappaB (NF-κB) p65, inducible nitric oxide synthase (iNOS) in livers. However, all these changes were dose-dependently reversed by LIM. Overall, the present findings demonstrated that LIM have the hepatoprotective effect through antioxidant and anti-inflammatory responses in Cd-exposure mice.     

Melatonin supplementation improves oxidative and inflammatory state in the blood of professional athletes during the preparatory period for competitions

Melatonin supplementation has been proved to have antioxidant and anti-inflammatory effects in humans. The aim of the study was to estimate the influence of a 30-day melatonin supplementation on oxidative and inflammatory state in the blood of intense training professional athletes. The study was conducted in 47 football players, 19 rowers, and 15 adults who did not practice sports (control group). Blood samples were taken once from the control group and twice from the athletes: before and after 30-day melatonin administration (5?mg daily before sleep). Serum levels of melatonin, isoprostanes, antiox-LDL antibodies, interleukin-6, and C-reactive protein were measured. In erythrocytes, the concentrations of reduced glutathione (GSH) and malondialdehyde (MDA), and the activities of glutathione peroxidase (GSH-Px), cytoplasmic superoxide dismutase (SOD-1), and glutathione reductase (GR) were determined. Melatonin supplementation caused a significant decrease in markers of oxidative stress and a significant increase in melatonin concentration and the activities of SOD-1 and GSH-Px in athletes. The obtained data showed increased oxidative stress and inflammatory processes in professional athletes during intense training and indicated that supplementation of melatonin in their daily diet may have a beneficial effect on the protection of tissues against the adverse action of RONS and inflammatory processes.     

Protective effect of 4,4′-diaminodiphenylsulphone against oxidative stress but not to apoptotic stress in human diploid fibroblasts

Abstract

The antibiotic drug 4,4′-diaminodiphenylsulphone (DDS) is used to treat several dermatologic diseases, including Hansen's disease. This study confirmed the antioxidant nature of DDS in hydrogen peroxide (H₂O₂)-induced oxidative stress and assessed its role in other apoptotic stresses in human diploid fibroblasts (HDFs). Oxidative stress was effectively reduced by DDS in a dose-dependent manner. Moreover, the oxidative stress-induced increases in the levels of the p53 and p21 proteins were inhibited by pre-treatment with DDS. In addition, H₂O₂ and DDS increased the level of cytochrome P450 (CYP450) IIE1 in HDFs, implicating a role for DDS in H₂O₂ scavenging via the activation of CYP450. DDS treatment increased the activity of catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the GSH/GSSG ratio, indicating activation of the glutathione system against oxidative stress. However, DDS showed no protective effects on HDFs against other apoptotic stimuli, such as thapsigargin and staurosporine, suggesting that DDS would act only against oxidative stress. Therefore, in addition to its antibiotic function, DDS is a potent antioxidant against H₂O₂-induced oxidative stress in HDFs.     

Effects of exogenous spermidine on antioxidant system of tomato seedlings exposed to high temperature stress

The effects of foliar spraying with spermidine (Spd) on antioxidant system in tomato (Lycopersicon esculentum Mill.) seedlings were investigated under high temperature stress. The high temperature stress significantly inhibited plant growth and reduced chlorophyll (Chl) content. Application of exogenous 1 mM Spd alleviated the inhibition of growth induced by the high temperature stress. Malondialdehyde (MDA), hydrogen peroxide (H₂O₂) content and superoxide anion (O₂) generation rate were significantly increased by the high temperature stress, but Spd significantly reduced the accumulation of reactive oxygen species (ROS) and MDA content under the stress. The high temperature stress significantly decreased glutathione (GSH) content and activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR) and dehydroascorbate reductase (DHAR), but increased contents of dehydroascorbic acid (DHA), ascorbic acid (AsA), and oxidized glutathione (GSSG) in tomato leaves. However, Spd significantly increased the activities of antioxidant enzymes, levels of antioxidants and endogenous polyamines in tomato leaves under the high temperature stress. In addition, to varying degrees, Spd regulated expression of MnSOD, POD, APX2, APX6, GR, MDHAR, DHAR1, and DHAR2 genes in tomato leaves exposed to the high temperature stress. These results suggest that Spd could change endogenous polyamine levels and alleviate the damage by oxidative stress enhancing the non-enzymatic and enzymatic antioxidant system and the related gene expression.     

Diel variation in cortisol,glucose, lactic acid and antioxidant system of black sea bass Centropristis striata under natural photoperiod

ABSTRACT

Diel rhythm in activity of antioxidant enzymes, as well as contents of glutathione and lipid peroxides, has been intensively investigated in Mammalia and Aves, however, the relevant studies about fish are few. In the present study, we examined variation in contents of cortisol, glucose and lactic acid in plasma of black sea bass Centropristis striata under natural photoperiod during a 24-h period. In addition, variation in activity of antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) and glutathione reductase (GR) as well as contents of total glutathione (T-GSH), reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) in liver and plasma of the fish were also determined. The plasma and liver samples were collected from the test fish at 3 h intervals during a 24-h cycle, with the first sampling time set at 03:00 h. No significant differences were found in glucose content and activities of GSH-PX and GR in plasma, as well as activities of SOD and GR in liver among different sampling times. In contrast, apparent variation was observed in contents of cortisol, lactic acid and MDA in plasma, activities of SOD and CAT in plasma, contents of MDA, T-GSH, GSH and GSSG in liver and activities of GSH-PX and CAT in liver between different sampling times. Moreover, contents of cortisol and MDA in plasma, SOD activity in plasma, and contents of MDA, GSH and GSSG in liver exhibited circadian rhythm, and their acrophases occurred at 06:08 h, 18:38 h, 15:09 h, 09:57 h, 23:36 h and 07:30 h, respectively. The present study indicates that some physiological parameters relating to stress response, such as cortisol and MDA contents in plasma, MDA, GSH and GSSG contents in liver and SOD activity in plasma changed at different time throughout a day in black sea bass. Therefore, caution should be taken when evaluating stress response in fish with these physiological parameters measured at different times.     

Oxidative Damage Induced by Arsenic in Mice or Rats: A Systematic Review and Meta-Analysis

In this meta-analysis, studies reporting arsenic-induced oxidative damage in mouse models were systematically evaluated to provide a scientific understanding of oxidative stress mechanisms associated with arsenic poisoning. Fifty-eight relevant peer-reviewed publications were identified through exhaustive database searching. Oxidative stress indexes assessed included superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione-s-transferase (GST), glutathione reductase (GR), oxidized glutathione (GSSG), malondialdehyde (MDA), and reactive oxygen species (ROS). Our meta-analysis showed that arsenic exposure generally suppressed measured levels of the antioxidants, SOD, CAT, GSH, GPx, GST, and GR, but increased levels of the oxidants, GSSG, MDA, and ROS. Arsenic valence was important and GR and MDA levels increased to a significantly (P < 0.05) greater extent upon exposure to As³⁺ than to As⁵⁺. Other factors that contributed to a greater overall oxidative effect from arsenic exposure included intervention time, intervention method, dosage, age of animals, and the sample source from which the indexes were estimated. Our meta-analysis effectively summarized a wide range of studies and detected a positive relationship between arsenic exposure and oxidative damage. These data provide a scientific basis for the prevention and treatment of arsenic poisoning.     

Neuroprotective effects of aucubin on hydrogen peroxide-induced toxicity in human neuroblastoma SH-SY5Y cells via the Nrf2/HO-1 pathway

BackgroundWhen redox balance is lost in the brain, oxidative stress can cause serious damage that leads to neuronal loss, in congruence with neurodegenerative diseases. Aucubin (AU) is an iridoid glycoside and that is one of the active constituents of Eucommia ulmoides, has many pharmacological effects such as anti-inflammation, anti-liver fibrosis, and anti-atherosclerosis.PurposeThe present study aimed to evaluate the inhibitory effects of AU on cell oxidative stress against hydrogen peroxide (H₂O₂)-induced injury in SH-SY5Y cells in vitro.MethodsSH-SY5Y cells were simultaneously treated with AU and H₂O₂ for 24 h. Cell viability was measured by CCK-8. Additionally, mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, and cell apoptosis were measured by flow cytometry.ResultsThe results showed that AU can significantly increase the H₂O₂-induced cell viability and the mitochondrial membrane potential, decrease the ROS generation, malondialdehyde (MDA), and increase glutathione (GSH) contents and the superoxide dismutase (SOD) activity. We also found that H₂O₂ stimulated the production of nitric oxide (NO), which could be reduced by treatment with AU through inhibiting the inducible nitric oxide synthase (iNOS) protein expression. In H₂O₂-induced SH-SY5Y cells, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) content and cell apoptosis were significantly reduced by AU treatment through nuclear factor E2-related factor 2/hemo oxygenase-1 (Nrf2/HO-1) activation, inhibiting the expression of p-NF-κB/NF-κB and down-regulating MAPK and Bcl-2/Bax pathways.ConclusionThese results indicate that AU can reduce inflammation and oxidative stress through the NF-κB, Nrf2/HO-1, and MAPK pathways.     

Oxidative stress in myelin sheath: The other face of the extramitochondrial oxidative phosphorylation ability

Abstract

Oxidative phosphorylation (OXPHOS) is not only the main source of ATP for the cell, but also a major source of reactive oxygen species (ROS), which lead to oxidative stress. At present, mitochondria are considered the organelles responsible for the OXPHOS, but in the last years we have demonstrated that it can also occur outside the mitochondrion. Myelin sheath is able to conduct an aerobic metabolism, producing ATP that we have hypothesized is transferred to the axon, to support its energetic demand.

In this work, spectrophotometric, cytofluorimetric, and luminometric analyses were employed to investigate the oxidative stress production in isolated myelin, as far as its respiratory activity is concerned. We have evaluated the levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), markers of lipid peroxidation, as well as of hydrogen peroxide (H₂O₂), marker of ROS production. To assess the presence of endogenous antioxidant systems, superoxide dismutase, catalase, and glutathione peroxidase activities were assayed. The effect of certain uncoupling or antioxidant molecules on oxidative stress in myelin was also investigated.

We report that isolated myelin produces high levels of MDA, 4-HNE, and H₂O₂, likely through the pathway composed by Complex I–III–IV, but it also contains active superoxide dismutase, catalase, and glutathione peroxidase, as antioxidant defense. Uncoupling compounds or Complex I inhibitors increase oxidative stress, while antioxidant compounds limit ROS generation.

Data may shed new light on the role of myelin sheath in physiology and pathology. In particular, it can be presumed that the axonal degeneration associated with myelin loss in demyelinating diseases is related to oxidative stress caused by impaired OXPHOS.     

Biomarkers of antioxidant status and lipid peroxidation in elderly patients with hypertension

Objective: The objective of the present study was to examine selected parameters of the blood redox system in elderly patients with hypertension.examine selected parameters of the blood redox system in elderly patients with hypertension. Methods: We analyzed differences in redox-associated molecules and enzymes among elderly hypertensive subjects (age above 65?years, n?=?49) and two groups of normotensive subjects (<65 years old – Control group I; n?=?27, and >65 – Control group II; n?=?30). Results: Decreased activity of antioxidant enzymes, increased lipid peroxidation and reduced production of nitric oxide were observed in hypertensive subjects, compared to healthy younger controls, or those of the same age. In healthy controls, an age-related decrease in the production of nitric oxide and the activities of SOD-1 and GPx-1 was also evident. The pathology of hypertension was characterised by further, significant decreases in the values of these parameters. When the subgroups of females and males were compared to their respective controls, a compromised redox balance was observed that was more evident in female hypertensives. Discussion: Hypertension in elderly patients is accompanied by changes in biomarkers of antioxidant status and lipid peroxidation status, which significantly differ from those observed in healthy ageing subjects. Our study also suggests that the relationship of gender and changes in redox balance with regard to hypertension should be further explored.     

Thymoquinone protects human retinal pigment epithelial cells against hydrogen peroxide induced oxidative stress and apoptosis

Oxidative stress in retinal pigment epithelium (RPE) cells may contribute to the progression of age-related macular degeneration. Thymoquinone (TQ), an active component derived from Nigella sativa, possesses antioxidative effect. However, the role of TQ in RPE cells under oxidative stress condition remains unclear. The present study aimed to examine the protective effect of TQ against hydrogen peroxide (H₂O₂)-induced oxidative stress in human RPE cells. Our results showed that TQ improved the cell viability and apoptosis in H₂O₂-induced ARPE cells. We also found that the levels of reactive oxygen species and malondialdehyde induced by H₂O₂ were reduced after the pretreatment of TQ. In addition, the inhibitory effect of H₂O₂ on the glutathione (GSH) level and superoxide dismutase activity was markedly attenuated by TQ pretreatment. Moreover, TQ enhanced the activation of Nrf2/heme oxygenase 1 (HO-1) signaling pathway in H₂O₂-induced ARPE cells. Knockdown of Nrf2 abolished the protective effect of TQ on H₂O₂-induced oxidative damage. These results suggested that TQ protected ARPE cells from H₂O₂-induced oxidative stress and apoptosis via the Nrf2/HO-1 signaling pathway.     

虎杖苷对老年小鼠术后认知功能障碍及海马氧化应激和神经炎症的影响

摘要 目的：探讨虎杖苷对老年小鼠术后认知功能障碍及海马氧化应激和神经炎症的影响。方法：C57BL/6J雄性老年小鼠,18月龄,体重24~28 g,随机分为4组：假手术组（Sham组）、术后认知功能障碍组（POCD组）、低剂量虎杖苷组（PD1组）、高剂量虎杖苷组（PD2组）。Sham组老年小鼠仅接受水合氯醛麻醉,不行外科手术;POCD组老年小鼠接受腹部手术以制备POCD老年动物模型;PD1组小鼠制备POCD模型,并于术后即刻、24 h和48 h分别腹腔注射低剂量虎杖苷25 mg/kg;PD2组小鼠制备POCD模型,并于术后即刻、24 h和48 h分别腹腔注射高剂量虎杖苷50 mg/kg。使用Morris水迷宫行为学实验评估老年小鼠术后认知功能,使用Western blot法检测术后小鼠海马Nrf2、HO-1、HMGB1、Iba-1蛋白水平,检测海马活性氧（ROS）、丙二醛（MDA）、超氧化物歧化酶（SOD）含量以反映术后海马氧化应激水平。结果：（1）与Sham组比较,POCD组老年小鼠术后逃离潜伏期显著增加（P<0.05）,穿越平台次数和目标象限停留时间下降（P<0.05）,海马Nrf2和HO-1蛋白表达水平明显降低（P<0.05）,氧化应激产物ROS和MDA含量增加（P<0.05）,抗氧化酶SOD活性降低（P<0.05）,Iba-1和HMGB1蛋白表达水平增加（P<0.05）;（2）与POCD组比较,PD1组和PD2组小鼠术后逃离潜伏期缩短（P<0.05）,穿越平台次数和目标象限停留时间增多（P<0.05）,海马Nrf2和HO-1蛋白表达水平升高（P<0.05）,ROS和MDA含量减少（P<0.05）,SOD活性增加（P<0.05）,Iba-1和HMGB1蛋白表达减少（P<0.05）。结论：虎杖苷可减轻老年小鼠术后认知功能损伤,缓解术后海马氧化应激和神经炎症,其机制可能与促进Nrf2/HO-1信号通路有关。     

Abortion-prone mating influences placental antioxidant status and adversely affects placental and foetal development

Abstract

Oxidative stress is associated with decreased female fertility and adversely affects prenatal development. Mammalian cells have developed a network of enzymatic and non-enzymatic antioxidant defence systems to prevent oxidative stress. Little attention has been paid to the antioxidative pathways in placentas of normal and disturbed pregnancies, leaving a gap in our knowledge about the role of antioxidants in the control of foeto-placental development. The challenges in studying early human pregnancy can partly be overcome by designing animal models of abnormal pregnancy. We aimed to determine whether the antioxidant status of placentas from the CBA/J × DBA/2 abortion-prone pregnant mice differed from that of normal pregnant mice. The foetal/placental weight ratio was lower in abortion-prone matings compared with that in non-abortion-prone matings. The increased placental malondialdehyde (MDA) content, the end products of lipid peroxidation, with concomitants alterations in placental antioxidants, namely copper-zinc containing superoxide dismutase (SOD1), manganese containing (SOD2), glutathione peroxidases (GPX), glutathione reductase (GR) and catalase (CAT) activities may be involved in placental and foetal growth restriction. We show that placental oxidative stress is linked with poor prenatal development and pregnancy losses in CBA/J × DBA/2 mice matings. This animal model may be useful in the evaluation of nutritional antioxidant therapies for oxidative stress and associated prenatal developmental disorders.