Neuroprotective Effect of HOTAIR Silencing on Isoflurane-Induced Cognitive Dysfunction via Sponging microRNA-129-5p and Inhibiting Neuroinflammation

<b><i>Introduction:</i></b> This article purposed to detect the function of the HOTAIR and HOTAIR/microRNA-129-5p (miR-129-5p) axis on the isoflurane (ISO)-injured cells and rat, and propounded a novel perspective in exploring the molecular pathogenesis of ISO damage. <b><i>Methods:</i></b> The expression of HOTAIR and miR-129-5p was tested by quantitative real-time PCR. The viable cells were identified using MMT, and the apoptotic cells were provided by flow cytometry. The concentration of proinflammatory indicators was revealed by enzyme-linked immunosorbent assay kits. The function of HOTAIR on oxidative stress was detected by commercial kits. A luciferase assay was performed to confirm the relationship between miR-129-5p and HOTAIR. The Morris water maze test was conducted to elucidate the cognition of SD rats. <b><i>Results:</i></b> The expression of HOTAIR was enhanced and the expression of miR-129-5p was lessened in the ISO-evoked SD rats and HT22 cells. The interference of HOTAIR reversed the injury of ISO on cell viability, apoptosis, inflammation, and oxidative stress. Besides, HOTAIR might be a target ceRNA of miR-129-5p. MiR-129-5p abrogated the function of silenced HOTAIR on cell viability, cell apoptosis, inflammation, and oxidative stress. Moreover, in vivo, the intervention of HOTAIR reversed the influence of ISO on cognition and oxidative stress by binding miR-129-5p. <b><i>Discussion/Conclusion:</i></b> Lowly expressed HOTAIR contributed to the recovery of the ISO-injured HT22 cell model from the abnormal viability, apoptosis, inflammation, and oxidative stress by regulating miR-129-5p. miR-129-5p mediated the function of HOTAIR on cognition and oxidative balance in the ISO-managed SD rat model.

The Oxidative Balance Orchestrates the Main Keystones of the Functional Activity of Cardiomyocytes

This review is aimed at providing an overview of the key hallmarks of cardiomyocytes in physiological and pathological conditions. The main feature of cardiac tissue is the force generation through contraction. This process requires a conspicuous energy demand and therefore an active metabolism. The cardiac tissue is rich of mitochondria, the powerhouses in cells. These organelles, producing ATP, are also the main sources of ROS whose altered handling can cause their accumulation and therefore triggers detrimental effects on mitochondria themselves and other cell components thus leading to apoptosis and cardiac diseases. This review highlights the metabolic aspects of cardiomyocytes and wanders through the main systems of these cells: (a) the unique structural organization (such as different protein complexes represented by contractile, regulatory, and structural proteins); (b) the homeostasis of intracellular Ca2+ that represents a crucial ion for cardiac functions and E-C coupling; and (c) the balance of Zn2+, an ion with a crucial impact on the cardiovascular system. Although each system seems to be independent and finely controlled, the contractile proteins, intracellular Ca2+ homeostasis, and intracellular Zn2+ signals are strongly linked to each other by the intracellular ROS management in a fascinating way to form a “functional tetrad” which ensures the proper functioning of the myocardium. Nevertheless, if ROS balance is not properly handled, one or more of these components could be altered resulting in deleterious effects leading to an unbalance of this “tetrad” and promoting cardiovascular diseases. In conclusion, this “functional tetrad” is proposed as a complex network that communicates continuously in the cardiomyocytes and can drive the switch from physiological to pathological conditions in the heart.

Antioxidant enzymes and vascular diseases

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a fundamental role in regulating endothelial function and vascular tone in the physiological conditions of a vascular system. However, oxidative stress has detrimental effects on human health, and numerous studies confirmed that high ROS/RNS production contributes to the initiation and progression of cardiovascular diseases. The antioxidant defense has an essential role in the homeostatic functioning of the vascular endothelial system. Endogenous antioxidative defense includes various molecules and enzymes such as superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. Together all these antioxidative enzymes are essential for defense against harmful ROS features. ROS are mainly generated from redox-active compounds involved in the mitochondrial respiratory chain. Thus, targeting antioxidative enzymes and mitochondria oxidative balance may be a promising approach for vascular diseases occurrence and treatment. This review summarized the most recent research on the regulation of antioxidative enzymes in vascular diseases.

Flight and dietary antioxidants influence antioxidant expression and activity in a migratory bird

Ecologically-relevant factors such as exercise and diet quality can directly influence how physiological systems work including those involved in maintaining oxidative balance; however, to our knowledge, no studies to date have focused on how such factors directly affect expression of key components of the endogenous antioxidant system (i.e., transcription factors, select antioxidant genes, and corresponding antioxidant enzymes) in several metabolically active tissues of a migratory songbird. We conducted a 3-factor experiment that tested the following hypotheses: (H1) Daily flying over several weeks increases the expression of transcription factors NRF2 and PPARs as well as endogenous antioxidant genes (i.e., CAT, SOD1, SOD2, GPX1, GPX4), and upregulates endogenous antioxidant enzyme activities (i.e., CAT, SOD, GPx). (H2) Songbirds fed diets composed of more 18:2n-6 PUFA are more susceptible to oxidative damage and thus upregulate their endogenous antioxidant system compared to when fed diets with less PUFA. (H3) Songbirds fed dietary anthocyanins gain additional antioxidant protection and thus upregulate their endogenous antioxidant system less compared to songbirds not fed anthocyanins. Flight training increased the expression of 3 of the 6 antioxidant genes and transcription factors measured in the liver, consistent with H1, but for only one gene (SOD2) in the pectoralis. Dietary fat quality had no effect on antioxidant pathways (H2) whereas dietary anthocyanins increased the expression of select antioxidant enzymes in the pectoralis, but not in the liver (H3). These tissue-specific differences in response to flying and dietary antioxidants are likely explained by functional differences between tissues as well as fundamental differences in their turnover rates. The consumption of dietary antioxidants along with regular flying enables birds during migration to stimulate the expression of genes involved in antioxidant protection likely through increasing the transcriptional activity of NRF2 and PPARs, and thereby demonstrates for the first time that these relevant ecological factors affect the regulation of key antioxidant pathways in wild birds. What remains to be demonstrated is how the extent of these ecological factors (i.e., intensity or duration of flight, amounts of dietary antioxidants) influences the regulation of these antioxidant pathways and thus oxidative balance.

Relationship between indicators of insulin resistance and oxidative balancein adolescents with androgen deficiency

The purpose of the work was to study the relationship between the indicators of insulin resistance (IR), free radical oxidation products (FRO) levels, and the antioxidant system activity in adolescents with androgen deficiency (AD).Materials and methods. 58 adolescents 13­—18 years old with AD were examined. Serum levels of total testosterone, glucose, insulin, tiobarbituric acid active compounds (TBA), carbonylated proteins (CB), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activity were determined. The HOMA index and the coefficient of oxidative stress were calculated.Results and discussion. In the group of adolescents with AD without IR, an inverse correlation was found between the HOMA index and CAT activity. CAT activity negatively correlated with CB content and glucose concentration. In addition, an inverse relationship was found between the activity of GPO and SOD. IR indices indirectly, through feedback with the activity of CAT, influence to the formation of conditions for inhibition/activation of FRO of proteins.IR was revealed in 37.9 % of the examined adolescents with AD. Direct relationship was recorded between IR indicators and markers of oxidative stress, as well as between testosterone levels and GPx activity in the group of these patients. Direct correlation between the coefficient of oxidative stress and the content of TBA-­active compounds indicates the formation of oxidative stress due to the activation of lipid peroxidation. Reduced testosterone levels in adolescents with AD inhibits an increase in GPx activity and prevents compensation for excessive intensity of free radical processes. Conclusion. The results indicate that adolescents with AD have a close relationship between the processes of carbohydrate metabolism, FRO, and antioxidant protection.In adolescents with AD without IR, a balancebetween the studied parameterswas found.The formation of IR in adolescents with AD shifts the equilibrium of the oxidative balance towards the activation of FRO processes. Decreased testosterone levels in adolescents with AD do not maintain the body’s antioxidant status within normal limits.

93 Melatonin and oxidative stress in the prevention of cardiovascular disease

Aims Arterial hypertension, especially if not well-controlled, is one of the main risk factors predisposing to fatal cardiovascular diseases (CVDs). Moreover, the diagnosis of essential hypertension are increasing, therefore oxidative stress and chronic inflammation have also been identified as potential responsible for the development of endothelial damage. Among all the molecules, melatonin (MT) was chosen for its role as a powerful antioxidant and anti-inflammatory endogenous molecule. This trial aims to evaluate the early intervention at the base of the inflammatory and oxidative cascade (that results in the development of hypertension), to restore an oxidative balance leading to positive results even at the endothelial and vascular level using MT in addition to anti-hypertensive therapy. Methods The trial is randomized, prospective and monocentric control. We enrolled 23 patients with hypertension in absence of other cardiovascular or autoimmune diseases that could alter the oxidative background, from March 2018 to April 2019 (recruitment period). Patients were randomly assigned to two groups: ‘melatonin group’ (in which 16 patients add 1 mg/day of melatonin for a year, to their already settled therapy), and a ‘control’ group (consisting of 7 patients with no changes in their therapy). The average follow-up was 1 year from randomisation. Patients were evaluated before and after a period of 1 year through MT plasma concentration and serum antioxidant capacity (TAC) by specific quantitative ELISA method. Therefore endothelial dysfunction and arterial stiffness were evaluated too (using the non-invasive methods of EndoPAT and SphygmoCor). Results In ‘melatonin group’ arterial stiffness index statistically decreased (P 0.022), according to a significant increase in plasma melatonin values (P 0.003) and significant decrease in TAC levels (P 0.041) despite the ‘control’ group. The improvement of endothelial function was not significant (P 0.688). Blood pressure had not a significative improvement too (P 0.401). Conclusions Data obtained could confirm the hypothesis of activation of plasma antioxidant system against a situation of altered oxidative balance. In fact, it is possible to hypothesize a correlation between TAC and arterial stiffness that confirm the antioxidant role of MT. The combination between antihypertensive therapy and antioxidant supplementation is able to improve the vascular stiffness. Data obtained are still preliminary and present some limitations but we can think of proposing this trial as a future basis for other extensive and prolonged studies.

Oxidative Stress and Pathogenesis in Malaria

Malaria is a highly inflammatory and oxidative disease. The production of reactive oxygen species by host phagocytes is an essential component of the host response to Plasmodium infection. Moreover, host oxidative enzymes, such as xanthine oxidase, are upregulated in malaria patients. Although increased production of reactive oxygen species contributes to the clearance of the parasite, excessive amounts of these free radicals can mediate inflammation and cause extensive damage to host cells and tissues, probably contributing to severe pathologies. Plasmodium has a variety of antioxidant enzymes that allow it to survive amidst this oxidative onslaught. However, parasitic degradation of hemoglobin within the infected red blood cell generates free heme, which is released at the end of the replication cycle, further aggravating the oxidative burden on the host and possibly contributing to the severity of life-threatening malarial complications. Additionally, the highly inflammatory response to malaria contributes to exacerbate the oxidative response. In this review, we discuss host and parasite-derived sources of oxidative stress that may promote severe disease in P. falciparum infection. Therapeutics that restore and maintain oxidative balance in malaria patients may be useful in preventing lethal complications of this disease.

Some indicators of free radical oxidation and antioxidant protection in the erythrocytes of former athletes

Objective: to study the main indicators of free radical oxidation and antioxidant protection in the erythrocytes of former athletes, depending on the period of termination of sports.Materials and methods: 24 former male athletes aged 19–29 years were examined, who were divided into 2 groups of 12 people each (1st group — former athletes who stopped training for up to 2 years; 2nd — over 2 years). The control group consisted of 15 practically healthy untrained student volunteers of the same age. In erythrocytes, spectrophotometrically (spectrophotometer Shimadzu 1240, Japan), the activity of antioxidant enzymes was determined: superoxide dismutase (SOD) (K.F. 1.15.1.1) — by inhibiting the reduction of nitro blue tetrazolium by superoxide anion radical at λ = 540 nm, after preliminary processing of erythrocytes by the method of Dubinina E.E. and others [8]; catalase (K.F. 1.11.1.6) — according to the rate of utilization of hydrogen peroxide at λ = 260 nm; glutathione peroxidase (HP) (KF 1.11.1.9) — by the change in the content of reduced glutathione in samples before and after incubation of the substrate with dithiobis-nitrobenzoic acid at λ = 412 nm; glutathione reductase (GR) (K.F. 1.6.4.2) — according to the catalytic NADPH ∙ H+-dependent transformation of the oxidized form of glutathione into the reduced form, the intensity of which was estimated by the rate of decrease in the extinction of samples at λ = 340 nm, at which the NADPH H+ solution has a maximum light absorption (Warburg test).Results: the direction of the shifts in the state of the oxidative balance was established depending on the period of detraining. A significantly lower value of the total antioxidant activity was revealed in the former athletes of the 1st group. This phenomenon is probably associated with a decrease in the efficiency of the enzymatic link of the antioxidant defense in the absence of regular physical exertion, and, as a consequence, an increased consumption of non-enzymatic antioxidants. It was found that the early post-sports period is characterized by significantly lower, in comparison with the control group, the values of the activity of the first-order enzymes (superoxide dismutase) against the background of the increased activity of the second-order enzymes (catalase).Conclusions: the obtained data can be recommended for monitoring the state of athletes who stopped playing sports and taken into account when prescribing rehabilitation measures for the corresponding contingent.

Apiaceae as an Important Source of Antioxidants and Their Applications

The excess level of reactive oxygen species (ROS) disturbs the oxidative balance leading to oxidative stress, which, in turn, causes diabetes mellites, cancer, and cardiovascular diseases. These effects of ROS and oxidative stress can be balanced by dietary antioxidants. In recent years, there has been an increasing trend in the use of herbal products for personal and beauty care. The Apiaceae (previously Umbelliferae) family is a good source of antioxidants, predominantly phenolic compounds, therefore, widely used in the pharmaceutical, cosmetic, cosmeceutical, flavor, and perfumery industries. These natural antioxidants include polyphenolic acids, flavonoids, carotenoids, tocopherols, and ascorbic acids, and exhibit a wide range of biological effects, including anti-inflammatory, anti-aging, anti-atherosclerosis, and anticancer. This review discusses the Apiaceae family plants as an important source of antioxidants their therapeutic value and the use in cosmetics.