Oxidant-antioxidant Homeostasis Research Articles

Oxidative and nitrosative stress — the leading mechanisms of chronic pancreatitis and chronic obstructive pulmonary disease interaction and inducers of their progression

Background. The frequency of chronic pancreatitis (CP) comorbidity with chronic obstructive pulmonary disease (COPD) has significantly increased recently. It may be accompanied by changes in oxidant-antioxidant homeostasis and activates a cascade of reactions of mutual burdening of these pathologies. The purpose of the current research was to evaluate the intensity of lipid peroxidation, oxidative modification of proteins and the state of individual factors of the antioxidant defense system in the development and course of CP, depending on the comorbid COPD. Materials and methods. Three hundred and seventeen patients were examined, including 62 patients with CP alone (group 1), 132 CP patients with comorbid COPD (group 2), 123 patients with COPD alone (group 3). The content in blood of isolated double bonds in compounds, conjugated dienes, ketodienes and conjugated trienes, malonic aldehyde, nitrites/nitrates, reduced glutathione, the activity of catalase, glutathione-S-transferase, glutathione peroxidase were evaluated in all patients. Results. In CP patients with comorbid COPD, the maximum oxidative stress intensity among the compared groups was registered. There was a reliable increase in the content of malonic aldehyde — by 2.0 times (p < 0.05), isolated double bonds — by 2.2 times (p < 0.05), conjugated dienes — by 1.9 times (p < 0.05), ketodienes and conjugated trienes — by 1.9 times (p < 0.05), nitrites/nitrates — by 2.6 times (p < 0.05). A reliable decrease in reduced glutathione content of erythrocytes was detec­ted: in group 1 — by 1.5 times, in group 2 — by 1.9 times (p < 0.05), in group 3 — by 1.2 times (p < 0.05). The compensatory increase in the activity of glutathione-S-transferase, glutathione peroxidase and blood catalase was revealed: in group 1 — by 1.3, 1.2 and 1.5 times (p < 0.05); in group 2 — by 1.5, 1.3 and 1.8 times (p < 0.05), in group 3 — by 1.2, 1.2 and 1.4 times, respectively (p < 0.05). Conclusions. The comorbid course of CP and COPD is accompanied by the maximum intensity of oxidative and nitrosative stress compared to the isolated course of the disease. An increase was detected in intermediate and final metabolites of peroxide oxidation in the blood, oxidative modification of proteins, nitrites/nitrates in the blood against the background of a deep imbalance of antioxidant defense factors, an increase in ceruloplasmin content in the blood, which requires the administration of antioxidant agents to correct detected disorders and prevent the progression of both comorbid diseases.

Nrf2-Mediated Antioxidant Defense and Thyroid Hormone Signaling: A Focus on Cardioprotective Effects.

Thyroid hormones (TH) perform a plethora of actions in numerous tissues and induce an overall increase in metabolism, with an augmentation in energy demand and oxygen expenditure. Oxidants are required for normal thyroid-cell proliferation, as well as for the synthesis of the main hormones secreted by the thyroid gland, triiodothyronine (T3) and thyroxine (T4). However, an uncontrolled excess of oxidants can cause oxidative stress, a major trigger in the pathogenesis of a broad spectrum of diseases, including inflammation and cancer. In particular, oxidative stress is implicated in both hypo- and hyper-thyroid diseases. Furthermore, it is important for the TH system to rely on efficient antioxidant defense, to maintain balance, despite sustained tissue exposure to oxidants. One of the main endogenous antioxidant responses is the pathway centered on the nuclear factor erythroid 2-related factor (Nrf2). The aim of the present review is to explore the multiple links between Nrf2-related pathways and various TH-associated conditions. The main aspect of TH signaling is described and the role of Nrf2 in oxidant-antioxidant homeostasis in the TH system is evaluated. Next, the antioxidant function of Nrf2 associated with oxidative stress induced by TH pathological excess is discussed and, subsequently, particular attention is given to the cardioprotective role of TH, which also acts through the mediation of Nrf2. In conclusion, the interaction between Nrf2 and most common natural antioxidant agents in altered states of TH is briefly evaluated.

Acute Nitrite Exposure Induces Dysfunction and Oxidative Damage in Grass Carp Isolated Hemocytes.

To evaluate the effects of nitrite on the oxidative damage of blood cells of Grass Carp Ctenopharyngodon idella, the isolated hemocytes were exposed to nitrite (0, 1, 10, or 100 mg/L) for up to 24 h. Hemoglobin (Hb) and methemoglobin (MetHb) concentrations, reactive oxygen species (ROS) and malondialdehyde (MDA) levels, mitochondrial membrane potential (∆Ψm), and antioxidant enzyme activity were assayed to assess hematological parameters and the antioxidant defense mechanism. Results showed a remarkable decrease in Hb concentration with increasing nitrite concentration after a 24-h exposure, while the MetHb concentration increased significantly in nitrite exposure groups. The levels of ROS, ∆Ψm, and MDA increased to varying degrees with increases in nitrite exposure concentration and time. The total antioxidant capacity, catalase (CAT) activity, glutathione peroxidase (GPx) activity, and glutathione content showed a trend of rising initially and then decreasing with prolonged exposure time. Superoxide dismutase (SOD) activity was higher in the 1-mg/L nitrite exposure group and lower in the 100-mg/L group than in the control. The relative messenger RNA expression ratios of cat, sod1, and gpx were up-regulated significantly in the 1- and 10-mg/L groups and then declined in the 100-mg/L group. Therefore, it can be concluded that nitrite exposure activates the antioxidant defense mechanism of Grass Carp hemocytes and that the balance of oxidant-antioxidant homeostasis will be undermined by higher nitrite doses or longer exposure periods.

THE BIDIRECTIONAL EFFECT OF CREATINE SUPPORTS THE MAINTENANCE OF OXIDANT-ANTIOXIDANT HOMEOSTASIS DURING EXERCISE

The importance of supplements used with exercise is increasing day by day. In this study, it was aimed to evaluate the effects of creatine monohydrate (CrM) supplementation with different intensities of exercise on oxidative stress through dynamic thiol disulfide homeostasis. Fourty two BALB/c mice were used and randomly divided into 6 groups; control (C), low-intensity exercise (LIE), high-intensity exercise (HIE), C+CrM (4% of daily diet), LIE+CrM, and HIE+CrM groups. Exercise groups were performed low-intensity (8m/min/30min/day) and high-intensity (24m/min/30min/day) exercise on a mouse treadmill for 8 weeks. At the end of the experimental period, the thiol disulfide homeostasis levels analyzed by using a new automated measurement technique. When the native thiol and total thiol values were examined the difference between the groups was statistically significant (respectively, p=0.029, p=0,035). Creatine intake with exercise decreased native thiol and total thiol levels. However, serum disulfide levels were lower in LIE+CrM compared to other study groups, but there was no statistically significant difference. It is thought that creatine supplementation with exercise reduces the thiol-disulfide homeostasis burden of the organism, and that after the depletion of creatine stores, the sustainability of oxidant-antioxidant homeostasis can be extended, thus prolonging the duration of antioxidant resistance.

Light radiation promoted stilbene accumulation in peanut sprouts: a response of the reestablishment of oxidant-antioxidant homeostasis

Light radiation promoted stilbene accumulation in peanut sprouts: a response of the reestablishment of oxidant-antioxidant homeostasis

Оксидантно-протиоксидантний гомеостаз при гастродуоденопатіях, індукованих нестероїдними протизапальними препаратами, у хворих на остеоартроз з урахуванням патогенних штамів Helicobacter pylori

Роль Helicobacter pylori (Hp) в патогенетичних механізмах розвитку гастродуоденопатій (ГДП), обумовлених нестероїдними протизапальними препаратами (НПЗП), у хворих на остеоартроз (ОА) є не­однозначною. Метою роботи було визначення зміни оксидантно-протиоксидантного гомеостазу при ГПД, індукованих НПЗП, у хворих на ОА залежно від наявності патогенних штамів Hp. Методи. Для виконання поставленої мети обстежено 68 хворих на ОА із супутніми Hp-асоційованими ГДП, індукованими НПЗП. Визначено штами Hp у калі, крові та біоптатах методом полімеразної ланцюгової реакції. Досліджено вміст продуктів окиснювальної модифікації білків — альдегід- і кетондинітрофенілгідразонів нейтрального характеру (АКДНФГ НХ), глутатіону відновленого (ГВ), активності глутатіонпероксидази (ГП) та глутатіон-S-трансферази (ГТ). Результати. В усіх обстежених пацієнтів спостерігали вірогідне зростання інтенсивності окиснювальної модифікації білків. Однак у хворих із супутнім Нр патогенним та ульцерогенним штамом cag A+/vac A+ АКДНФГ НХ були відповідно вище на 13,55 % (р < 0,05) та 22,89 % (р < 0,05) порівняно з хворими із супутніми Нр cag A+/vac A– та Нр cag A–/vac A+. В обстежених хворих спостерігалося зниження вмісту ГВ на тлі компенсаторного зростання активності ГТ і ГП. У досліджуваних із Нр патогенним та ульцерогенним штамом cag A+/vac A+ вміст ГВ був вірогідно нижчим відповідно на 16,45 та 26,66 % порівняно з хворими із супутніми Нр cag A+/vac A– та Нр cag A–/vac A+. Активність ГТ і ГП у хворих із Нр, що містили штами cag A+/vac A–, були дещо вищими, ніж у пацієнтів із Нр, що містили штами cag A–/vac A+. Висновок. При гастродуоденопатіях, індукованих НПЗП, у хворих на ОА спостерігаються вірогідні зміни оксидантно-протиоксидантного гомеостазу, а супутній патогенний та ульцерогенний штам Hp cag A+/vac A+ сприяє інтенсифікації окиснювальної модифікації білків на тлі порушення функціонування системи протиоксидантного захисту.

Myrislignan Induces Redox Imbalance and Activates Autophagy in Toxoplasma gondii.

Toxoplasma gondii (T. gondii) is an important health problem in human and animals, and the highlighting side effects of launched therapeutic chemicals cannot be ignored. Thus, it is urgent to develop new drugs to against the infection. Myrislignan originated from nutmeg exhibited excellent anti-T. gondii activity in vitro and in vivo, and was able to destroy mitochondrial function. However, the exact mechanism of action is still unknown. In this study, combining RNAs deep-sequencing analysis and surface plasmon resonance (SPR) analysis, the differentially expressed genes (DEGs) and high affinity proteins suggested that myrislignan may affect the oxidation-reduction process of T. gondii. Furthermore, the upregulating ROS activity after myrislignan incubation verified that myrislignan destroyed the oxidant-antioxidant homeostasis of tachyzoites. Transmission electron microscopy (TEM) indicated that myrislignan induced the formation of autophagosome-like double-membrane structure. Moreover, monodansyl cadaverine (MDC) staining and western blot further illustrated autophagosome formation. Myrislignan treatment induced a significant reduction in T. gondii by flow cytometry analysis. Together, these findings demonstrated that myrislignan can induce the oxidation-reduction in T. gondii, lead to the autophagy, and cause the death of T. gondii.

Parameters of Oxidative Stress, Vitamin D, Osteopontin, and Melatonin in Patients with Lip, Oral Cavity, and Pharyngeal Cancer.

Lip, oral cavity, and pharyngeal cancers (LOCP) constitute a group of rare neoplasms with unfavorable prognosis. So far, not much is known about the role of vitamin D and oxidative stress in the pathogenesis of LOCP in the European population. The aim of the study was to determine the concentrations of vitamin D, osteopontin, melatonin, and malondialdehyde (MDA) as markers of oxidative stress and/or inflammation, as well as the activities of antioxidant enzymes in the course of LOCP. The vitamin D, melatonin, and osteopontin concentrations in blood serum, the MDA levels in erythrocytes and blood plasma, and the activities of superoxide dismutase (SOD-1), catalase (CAT), and glutathione peroxidase (GPx) in erythrocytes were measured in blood samples taken from 25 LOCP patients of middle age (YCG), 20 LOCP elderly patients (OCG), and 25 healthy middle-aged volunteers. In both cancer groups, decreases in vitamin D and CAT, as well as increases in osteopontin and blood plasma MDA, were observed. An increase in GPx activity in YCG and a decrease in melatonin level in OCG were found. The results indicate the vitamin D deficiency and disturbed oxidant-antioxidant homeostasis in LOCP patients. Osteopontin seems to be associated with LOCP carcinogenesis and requires further research.

Влияние [(1-фенил-5-формил-1<I>H</I>-имидазол-4-ил)тио]уксусной кислоты на антиоксидантный статус печени и почек крыс при интоксикации тетрахлорметаном

Исследовано влияние [(1-фенил-5-формил-1H-имидазол-4-ил)тио]уксусной кислоты на оксидантно-антиоксидантный гомеостаз в организме крыс при интоксикации тетрахлорметаном. Установлено, что под влиянием данного соединения большинство исследуемых показателей оксидантно-антиоксидантного равновесия в печени и почках животных в условиях токсического гепатита изменялись в сторону нормы. Полученные результаты указывают на способность соединений исследуемого типа угнетать процессы свободнорадикального окисления липидов и окислительной модификации белков, а также активировать системы антиоксидантной защиты в тканях животных.

Analyzing dose dependency of antioxidant defense system in the cyanobacterium Nostoc muscorum Meg 1 chronically exposed to Cd2+

The aim of the present study was to analyze the dose dependency of oxidant-antioxidant homeostasis in Cd2+ exposed Nostoc muscorum Meg 1 cells. Quantification of percent DNA loss, protein oxidation and lipid peroxidation was carried out to assess Cd2+ induced ROS mediated damages to the organism. The countermeasures adopted by the cyanobacterium were also evaluated by computing various components of both enzymatic and non-enzymatic antioxidants. Exposure to different Cd2+ (0.1, 0.2, 0.3, 0.5, 1, 1.5, 2, 2.5, 3 ppm) doses showed substantial increase in ROS content in the ranges of 20–181% and 116–323% at the end of first and seventh day. The DNA damage, protein oxidation and lipid peroxidation were increased by 11–62%, 7–143% and 13–183% with increasing Cd2+ concentrations at the end of seven days. TEM images clearly showed damages to the cell wall, cell membrane and thylakoid organization at higher Cd2+ (0.5–3 ppm) concentrations. Cd2+ exposure up to 0.5 ppm registered increase in contents of antioxidative enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR)) and in non-enzymatic antioxidants (glutathione, total thiol, phytochelatin and proline) indicating stimulation of ROS mitigating machinery. However, toxicity of Cd2+ was evident as at higher concentrations the cellular morphology and ultra-structures were negatively affected and the capacities of the cells to generate various antioxidant measures were highly compromised. The organism registered 96–98% sorption ability from a solution supplemented with 0.3 ppm Cd2+ and thus show realistic potential as Cd2+ bioremediator in wastewater treatment.

An Investigation of the Dynamic Thiol/Disulfide Homeostasis, As a Novel Oxidative Stress Plasma Biomarker, in Children With Autism Spectrum Disorders.

We aimed to investigate the role of impaired oxidant-antioxidant homeostasis on the etiopathogenesis of autism with a novel oxidative stress (OS) marker, dynamic thiol/disulfide homeostasis (DTDH), and relationship between the symptom severity and markers. A total of 60 children with ASD aged 3-10 years and 54 unaffected children were investigated for the plasma DTDH parameters. A sociodemographic-data form, K-SADS-PL, Childhood Autism Rating Scale, Abnormal Behavior Checklist, Autism Behavior Checklist, and a developmentally appropriate IQ test were administered to all participants. Distortion of DTDH to the OS-side in the autism group was determined with lower plasma levels of native and total thiol, in contrast to a higher disulfide and thiol oxidation-reduction ratio. However, biomarkers had no correlation with the symptom severity of autism. Cutoff values for each parameter on the ROC curve might be useful to predict ASD and each DTDH biomarker was detected as an independent predictor of ASD. The present study demonstrated a disturbed redox status and absence of an expected compensatory increase in antioxidant response in a pediatric sample of ASD by measuring dynamic oxidation/reduction shifts with a novel, practical and reproducible analytical technique, and contributes to data regarding oxidative hypothesis on autism and raises the question of the place of antioxidants in autism treatment. Our results may suggest predictive usefulness of the plasma DTDH biomarkers in ASD, despite the study being conducted with a modestly small sample size that makes further research with a larger replication sample necessary to substantiate the findings. LAY SUMMARY: Dynamic thiol/disulfide homeostasis is a novel plasma marker used to determine the oxidative stress which is a natural result of disequilibrium between the oxidants and antioxidants in the human body. There is increasing interest regarding a central biological linking role of oxidative stress among the other etiological factors of autism. Our findings on the disturbed plasma dynamic thiol/disulfide homeostasis in children with autism and the absence of an expected antioxidant response against increased oxidative stress supports the data concerning the role of oxidative stress on the etiology of autism and the need of further research on the place of antioxidants in autism treatment.

Phillyrin Mitigates Apoptosis and Oxidative Stress in Hydrogen Peroxide-Treated RPE Cells through Activation of the Nrf2 Signaling Pathway.

Oxidative stress-induced dysfunction or apoptosis in retinal pigment epithelial (RPE) cells is an important cause of dry age-related macular degeneration (AMD). Although phillyrin has been shown to exert significant antioxidant effects, the underlying mechanism of action remains unclear. The purpose of this study was to investigate the protective effect of phillyrin on hydrogen peroxide- (H2O2-) induced oxidative stress damage in RPE cells and the potential mechanism involved. It was found that phillyrin significantly protected RPE cells from H2O2 cytotoxicity. Furthermore, phillyrin alleviated oxidative stress-induced apoptosis via inhibition of endogenous and exogenous apoptotic pathways. Compared with the H2O2-treated group, the expressions of cleaved caspase-3, cleaved caspase-9, cleaved polymerase (PARP), death receptor Fas, and cleaved caspase-8, as well as Bax/Bcl-2 ratio were decreased in RPE cells after the phillyrin intervention. In addition, phillyrin reversed the oxidative stress-induced reductions in superoxide dismutase (SOD) and glutathione (GSH) levels and annulled the elevations in reactive oxygen species (ROS) and malondialdehyde (MDA), thereby restoring oxidant-antioxidant homeostasis. Phillyrin treatment upregulated the expressions of cyclin E, cyclin-dependent kinase 2 (CDK2), and cyclin A and downregulated the expressions of p21 and p-p53, thereby reversing the G0/G1 cell cycle arrest in H2O2-treated RPE cells. Pretreatment with phillyrin also increased the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), total Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductases-1 (NQO-1) in RPE cells and inhibited the formation of Kelch-like ECH-associated protein 1 (Keap1)/Nrf2 protein complex. Thus, phillyrin effectively protected RPE cells from oxidative stress through activation of the Nrf2 signaling pathway and inhibition of the mitochondria-dependent apoptosis pathway.

CLINICAL EFFECTIVENESS OF ANTRAL IN PATIENTS WITH CHRONIC PANCREATITIS

The studies on the pathogenesis of chronic pancreatitis (CP) have proven the important role of systemic inflammation, factors of proteinase-inhibitory system with increasing damaging effects of systemic proteolysis, disturbance of oxidant-antioxidant homeostasis, changes in blood lipid and protein spectroscopic processes that collectively contribute to inhibition of reparative processes and the activation of pancreatic fibrosis processes. The aim of this study was to determine the effectiveness of applying Antral medicine in the treatment of CP in the exacerbation phase on the basis of a comprehensive assessment of clinical course of CP and structural and functional disorders of the pancreas. Material and methods. 52 patients with CP of mixed aetiology were examined in the exacerbation phase of moderate severity. The first group (group 1, control) included 24 people, who received standard treatment within 30 days. The main group (group 2) involved 28 people, who in addition to the standard therapy took Antral (Pharmak OAO, Kyiv) in a dose of 1 tablet (200 mg) 3 times a day for 30 days. The comparison group consisted of 30 healthy individuals of the same age and sex. Results. In 4 weeks since the beginning of the therapy, the astheno-vegetative syndrome was found as significantly less manifested in only 2 people (7.1%) of the 2 groups, whereas in the 1 group it remained in 17 patients. At the same time in all patients of group 2 (100.0%) the pain and feeling of heaviness in the epigastric region, pain in the left and right subcostal area were disappeared, they did not complain of nausea.
 The restoration of physical performance in 100.0% of patients in the 2 group can be regarded as a positive manifestation of the therapy efficacy. Analyzing the indicators, which characterize the phase of CP exacerbation, it is necessary to note the patients of the 2 group demonstrated higher efficacy of their treatment program. Thus, dynamic indicators of blood α-amylase activity against the background of hyperfermentemia diagnosed prior the treatment and in the phase of CP exacerbation significantly decreased in both groups of observation on the 30th day of the therapy; the syndrome of enzyme rejection in the blood was eliminated in 100% of patients of the 2 groups; whereas in group 1 this was observed only in 58.3% of the patients. The dynamic of indicators of the inflammation syndrome in patients with CP (by blood C-reactive protein content) indicates its complete elimination in 96.4% of the patients in group 2 vs. 29.2% of the patients in group 1. Analysis of the dynamic indicators of elastase-1 content in the faeces of the patients with CP on the 30th day of the therapy indicates a significant increase in this indicator in only group 2. Restoration of the secretory capacity of the pancreas was observed in 78.6% of patients in group 2 vs. 20.8% of the patients in group 1. Conclusions. Complex therapy of patients with chronic pancreatitis with applying Antral in addition to the integrated therapy has led to faster, when compared with only standard therapy, achieving clinical remission of chronic pancreatitis, elimination of inflammatory pancreatic oedema, hyperfermentemia and inflammation, restoration of the external secretion of the pancreas.

A novel basic helix-loop-helix transcription factor, ZjICE2 from Zoysia japonica confers abiotic stress tolerance to transgenic plants via activating the DREB/CBF regulon and enhancing ROS scavenging.

ZjICE2 works as a positive regulator in abiotic stress responses and ZjICE2 is a valuable genetic resource to improve abiotic stress tolerance in the molecular breeding program of Zoysia japonica. The basic helix-loop-helix (bHLH) family transcription factors (TFs) play an important role in response to biotic or abiotic stresses in plants. However, the functions of bHLH TFs in Zoysia japonica, one of the warm-season turfgrasses, remain poorly understood. Here, we identified ZjICE2 from Z. japonica, a novel MYC-type bHLH transcription factor that was closely related to ICE homologs in the phylogenetic tree, and its expression was regulated by various abiotic stresses. Transient expression of ZjICE2-GFP in onion epidermal cells revealed that ZjICE2 was a nuclear-localized protein. Also, ZjICE2 bound the MYC cis-element in the promoter of dehydration responsive element binding 1 of Z. japonica (ZjDREB1) using yeast one-hybrid assay. A phenotypic analysis showed that overexpression of the ZjICE2 in Arabidopsis enhanced tolerance to cold, drought, and salt stresses. The transgenic Arabidopsis and Z. japonica accumulated more transcripts of cold-responsive DREB/CBFs and their downstream genes than the wild type (WT) after cold treatment. Furthermore, the transgenic plants exhibited an enhanced Reactive oxygen species (ROS) scavenging ability, which resulted in an efficient maintenance of oxidant-antioxidant homeostasis. In addition, overexpression of the ZjICE2 in Z. japonica displayed intensive cold tolerance with increases in chlorophyll contents and photosynthetic efficiency. Our study suggests that ZjICE2 works as a positive regulator in abiotic stress responses and the ICE-DREB/CBFs response pathway involved in cold stress tolerance is also conserved in Z. japonica. These results provide a valuable genetic resource for the molecular breeding program especially for warm-season grasses as well as other leaf crop plants.

ROLE OF OXIDATIVE STRESS IN PATHOGENESIS AND PROGRESSION OF NON-ALCOHOLIC STEATOHEPATITIS IN PATIENTS WITH CONCOMITANT CORONARY HEART DISEASE

The aim of the study: to investigate the state of the system of oxidant-antioxidant homeostasis in patients with NASH and comorbid coronary heart disease. Material and methods. We examined 86 patients with NASH, including 30 patients with NASH and obesity of I-II degree (group 1) and 56 patients with NASH and comorbid coronary heart disease (stable angina pectoris I-II) (group 2). The control group consisted of 30 healthy individuals of the comparable age. The average age of patients was 56,6 ± 5,74 years. Results. An essential pathogenetic factor for the onset and progression of NASH in the presence of comorbid coronary heart disease is the intensification of the processes of free radical lipids oxidation that determines the degree of activity of the pathological process in the liver: the accumulation of intermediate (isolated double bonds, diene conjugates, ketodiens and conjugated trienes) and terminal (malonic aldehyde of plasma and erythrocytes) products of lipid peroxidation against the background of disintegration of the system of antioxidant protection (reduction of the content of glutathione reduced in erythrocytes, compensatory growth of catalase activity). Insufficiency and disintegration in the system of antioxidant protection is one of the main factors resulting in the increase in metabolic intoxication, while preserving of glutathione in a reduced form is necessary to prevent the inactivation of a number of enzymes, protecting the hepatocyte membranes from the effects of oxidants. The oxidation of reduced glutathione leads to decrease in the intensity of glycolysis, lowered synthesis of ATP and decline in the energy potential of hepatocytes and cardiomyocytes that is particularly undesirable for the comorbidity of NASH and coronary heart disease.

MATERNAL OXIDANT-ANTIOXIDANT HOMEOSTASIS DURING NORMOTENSIVE AND PREECLAMPTIC PREGNANCY.

10Jul 2018 MATERNAL OXIDANT-ANTIOXIDANT HOMEOSTASIS DURING NORMOTENSIVE AND PRE-ECLAMPTIC PREGNANCY. Ehab Barakat MD , Ahmed M Hagras MD and Adel Al - Kholy MD. Departments of Obstetrics & Gynecology. Medical Biochemistry. Faculty of Medicine Benha and Tanta Universities.

Pathogenetic aspects of psoriasis in the metabolic disorders

Pathogenic mechanisms of psoriasis based but rather considered in scientific circles hereditary component, and even on the mechanisms of metabolic changes in the functioning of various organs and tissues that are not well understood. Key mechanisms of psoriasis researchers include disorders in lipid and carbohydrate metabolism, as well as changes in the antioxidant system of cells. The leading role in the pathogenesis of psoriasis in the scientific literature confer on oxidant-antioxidant homeostasis, which is associated with the adaptive-compensatory mechanisms of neurohumoral and metabolic control. This review reveals the feasibility of further, more in-depth studies of pathogenetic mechanisms of development of psoriasis based on the study of metabolic disorders in this pathology.

Role of PGC‐1α signaling in skeletal muscle health and disease

This paper reviews the current understanding of the molecular basis of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)–mediated pathway and discusses the role of PGC-1α in skeletal muscle atrophy caused by immobilization. PGC-1α is the master transcription regulator that stimulates mitochondrial biogenesis, by upregulating nuclear respiratory factors (NRF-1, 2) and mitochondrial transcription factor A (Tfam), which leads to increased mitochondrial DNA replication and gene transcription. PGC-1α also regulates cellular oxidant–antioxidant homeostasis by stimulating the gene expression of superoxide dismutase-2 (SOD2), catalase, glutathione peroxidase 1 (GPx1), and uncoupling protein (UCP). Recent reports from muscle-specific PGC-1α overexpression underline the importance of PGC-1α in atrophied skeletal muscle, demonstrate enhancement of the PGC-1α mitochondrial biogenic pathway, and reduced oxidative damage. Thus, PGC-1α appears to play a protective role against atrophy-linked skeletal muscle deterioration.

Natural Terpenes Prevent Mitochondrial Dysfunction, Oxidative Stress and Release of Apoptotic Proteins during Nimesulide-Hepatotoxicity in Rats

Nimesulide, an anti-inflammatory and analgesic drug, is reported to cause severe hepatotoxicity. In this study, molecular mechanisms involved in deranged oxidant-antioxidant homeostasis and mitochondrial dysfunction during nimesulide-induced hepatotoxicity and its attenuation by plant derived terpenes, camphene and geraniol has been explored in male Sprague-Dawley rats. Hepatotoxicity due to nimesulide (80 mg/kg BW) was evident from elevated SGPT, SGOT, bilirubin and histo-pathological changes. Antioxidants and key redox enzymes (iNOS, mtNOS, Cu/Zn-SOD, Mn-SOD, GPx and GR) were altered significantly as assessed by their mRNA expression, Immunoblot analysis and enzyme activities. Redox imbalance along with oxidative stress was evident from decreased NAD(P)H and GSH (56% and 74% respectively; P<0.001), increased superoxide and secondary ROS/RNS generation along with oxidative damage to cellular macromolecules. Nimesulide reduced mitochondrial activity, depolarized mitochondria and caused membrane permeability transition (MPT) followed by release of apoptotic proteins (AIF; apoptosis inducing factor, EndoG; endonuclease G, and Cyto c; cytochrome c). It also significantly activated caspase-9 and caspase-3 and increased oxidative DNA damage (level of 8-Oxoguanine glycosylase; P<0.05). A combination of camphene and geraniol (CG; 1∶1), when pre-administered in rats (10 mg/kg BW), accorded protection against nimesulide hepatotoxicity in vivo, as evident from normalized serum biomarkers and histopathology. mRNA expression and activity of key antioxidant and redox enzymes along with oxidative stress were also normalized due to CG pre-treatment. Downstream effects like decreased mitochondrial swelling, inhibition in release of apoptotic proteins, prevention of mitochondrial depolarization along with reduction in oxidized NAD(P)H and increased mitochondrial electron flow further supported protective action of selected terpenes against nimesulide toxicity. Therefore CG, a combination of natural terpenes prevented nimesulide induced cellular damage and ensuing hepatotoxicity.

Protective Role of l-Arginine Against Free-Radical Mediated Oxidative Damage in Patients with Unstable Angina.

Unstable angina is a critical condition of heart resulting from narrowing of vessels supplying blood to heart. Ischemia of the myocardium leads to oxidative stress and severe tissue damage. The objective of the present study was to determine the effect of l-arginine administration on the oxidant-antioxidant homeostasis which otherwise gets imbalanced in patients with cardiovascular diseases. The results obtained, show improvement in the oxidant-antioxidant levels of the subjects upon incorporation of l-arginine. Our findings suggest that supplementation of l-arginine along with regular anti-anginal therapy may be beneficial to the patients of unstable angina.