The effect of aqueous extract of Iranian oak (Quercus brantii) on antioxidant capacity and oxidative stress in beta-thalassemia patients: Randomized controlled trial.

BACKGROUND AND AIM: Frequent administration of blood in ß-thalassemia patients can lead to over-loaded iron, a reduction in the levels of antioxidant activities in the body, and oxidative stress. This study was done to evaluate the antioxidant and protective effect of aqueous oak (Quercus brantii) extract supplementation on these patients. METHODS: This clinical trial was performed on 60 major ß thalassemia patients dividing them into intervention and control groups. In addition to taking desferrioxamine (DFO), the control and intervention groups received respectively placebo capsule supplementation and aqueous Quercus extract capsules (300 mg/day) for 3 months. Serum lipid profiles (LDL-c, HDL-c, triglyceride), Total Antioxidant Capacity (TAC), Glucose, Uric acid, urea nitrogen (BUN), Creatinine, LFT (Liver Function Tests) such as SGOT, SGPT, ALP, Total bilirubin, Direct bilirubin, ferritin, MDA and carbonyl protein (CO) levels were measured before and after the period. In addition, the activity of catalase (CAT), and superoxide dismutase (SOD) was measured in the red blood cell. Furthermore, antioxidant activity and total phenolic content of aqueous Quercus were recorded to standardize capsule formulation. RESULTS: Mean serum MDA, and protein CO, significantly decreased in the intervention group with ß-TM after 3 months of treatment with Quercus extract. In addition, the superoxide dismutase (SOD) enzyme and Total antioxidant capacity (TAC) significantly increased in comparison with the control group. Changes in serum creatinine, BUN, and alanine transferase were not significant. In the study, Quercus extract capsules contain 48/56 mg gallic acid/g (dry extract) total phenol, 58/6 mg/g (dry extract), and flavonoids of 63/8 µg/ml antioxidant power which by GC/MS analysis has been measured. At the end of the study, serum MDA decreased from 48.65 ± 8.74 to 43.94 ± 10.39 µ mol/l after administration of oak extract and protein CO dropped from 2.44 ± 0.38 to 1.2 ± 0.31 nmol DNPH/mg protein after administration of the oak extract. At the end of the study serum, TAC increased in patients interventional group from 907 ± 319 to 977 ± 327 µmol FeSO4/l compared to the control group 916 ± 275 to 905.233 ± 233 µmol FeSO4/l with placebo, and SOD increased from 1577 ± 325 to 2079 ± 554 U/l (compared to 1687 ± 323 U/l with placebo). The treatment effect of Quercus was measured using a mixed-effects model of variance analysis for changes in MDA, protein CO, TAC, and SOD, with significant effects being demonstrated for each laboratory parameter (P = 0.15, P = 0.001, P = 0.02, and P < 0.003, respectively). CONCLUSIONS: Aqueous Quercus extract, due to its high antioxidant potential, reduced MDA, serum carbonyl protein, and increased superoxide dismutase activity effectively decreased serum OS and enhanced serum antioxidant capacity in patients with ß-thalassemia major. oak given as an adjuvant therapy to standard iron chelators may provide an improvement in the OS measurements obtained in these patients. REGISTRATION INFORMATION: This study was submitted, evaluated, and approved by the Iranian Registry of Clinical Trials (IRCT: http://www.irct.ir; IRCT2015101411819N4), which was established for national medical schools in Iran.

Catalase Activity of IgG and κκ-IgG, λλ-IgG, and κλ-IgG Subfractions in HIV-Infected Patients and Healthy Donors.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with pronounced oxidative stress, leading to the development of various virus-associated pathologies. A wealth of evidence suggests that, along with canonical enzymes of reactive oxygen species regulation, human blood contains antibodies with peroxidase, superoxide dismutase, and catalase activities. Here we show that the catalase activity of IgGs and their κκ-IgG, λλ-IgG, and κλ-IgG subfractions of HIV-infected individuals is significantly different compared to the healthy donors. METHODS: Protein G-Sepharose sorbent was used to resolve IgG from blood of healthy donors and HIV-infected patients by affinity chromatography. Subfractions of κκ-IgG, λλ-IgG, and κλ-IgG were separated from IgGs samples of each group by affinity chromatography on sorbents containing immobilized antibodies to κ or λ light human chains. The IgG catalase activity level was measured spectrophotometrically by evaluating the decrease in optical density (A240) due to hydrogen peroxide decomposition. RESULTS: The relative catalase activity of antibodies from HIV-infected patients (kcat = (1.41 ± 0.92) × 103 min-1, 95% CI: [1.01-1.81]) was statistically significant, 1.6 times higher (p = 0.014) compared to apparently healthy donors ((0.86 ± 0.49) × 103, 95% CI: [0.69-1.03]). The activity level of κκ-IgG HIV-infected patients ((0.44 ± 0.04) × 103 min-1) was 1.4 times higher than that of λλ-IgGs ((0.31 ± 0.025) × 103 min-1); the opposite was observed for κκ-IgGs from apparently healthy donors, which activity ((0.17 ± 0.015) × 103 min-1) was 3.1 times lower compared to λλ-IgGs ((0.53 ± 0.045) × 103 min-1). CONCLUSIONS: Thus, the data obtained may indicate that IgG with increased catalase activity may prevent harmful processes arising from oxidative stress in HIV-infected patients, acting as an additional natural molecular mechanism of regulation of hydrogen peroxide level.

[Correlation between CRAB Symptoms and Antioxidant Enzyme Activity in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the relationship between clinical indicators of CRAB symptoms and antioxidant enzyme activity in patients with multiple myeloma (MM). METHODS: The activity of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in the bone marrow supernatants of 44 patients with MM and 12 patients with non-malignant hematological diseases was detected by colorimetric assay, and then the differences in the activity of antioxidant enzymes between the two groups were compared. Furthermore, the relationship between the activity of antioxidant enzymes in the MM group and the levels of serum calcium, serum creatinine (Scr), hemoglobin (Hb), alkaline phosphatase (ALP) as well as bone lesions were analyzed. RESULTS: The antioxidant enzyme activity was lower in MM patients compared with the control group (P < 0.05). When the concentrations of serum calcium and ALP were higher than the normal levels, Hb was lower than 85 g/L, and there were multiple bone lesions, the activity of CAT, SOD and GPX was significantly declined (P < 0.05); When the concentration of Scr≥177 µmol/L, the activity of GPX was significantly declined (P < 0.05). Regression analyses showed that CAT, SOD and GPX were negatively correlated with serum calcium (r =-0.538, r =-0.456, r =-0.431), Scr (r =-0.342, r =-0.384, r =-0.463), and ALP (r =-0.551, r =-0.572, r =-0.482). CONCLUSION: The activity of antioxidant enzymes, including CAT, SOD and GPX, were decreased in patients with MM and they were negatively correlated with some clinical indicators of CRAB symptoms (such as serum calcium, Scr, and ALP), which suggests that promoting the activity of antioxidant enzymes may be beneficial to treat the CRAB symptoms of the patients with MM.

Catalase and interleukin-6 serum elevation in a prediction of treatment-resistance in male schizophrenia patients.

BACKGROUND: Oxidative stress (OS) and neuroinflammatory pathways play an important role in the pathophysiology of schizophrenia. The present study investigated the relationship between OS, inflammatory cytokines, and clinical features in male patients with treatment-resistant schizophrenia (TRS). METHOD: We measured plasma OS parameters, including manganese-superoxide dismutase (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD), total-SOD (T-SOD), malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase (GSH-Px); and serum inflammatory cytokines, including interleukin (IL)- 1α, IL-6, tumor necrosis factor-alpha (TNF-α), and interferon (IFN)-γ, from 80 male patients with chronic schizophrenia (31 had TRS and 49 had chronic stable schizophrenia (CSS)), and 42 healthy controls. The severity of psychotic symptoms was evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Compared with healthy controls, plasma Mn-SOD, CuZn-SOD, T-SOD, GSH-Px, and MDA levels were significantly lower, while CAT and serum IL-6 levels were higher in both TRS and CSS male patients (all P < 0.05). Significant differences in the activities of CAT (F = 6.068, P = 0.016) and IL-6 levels (F = 6.876, P = 0.011) were observed between TRS and CSS male patients after analysis of covariance. Moreover, a significant positive correlation was found between IL-6 levels and PANSS general psychopathology subscores (r = 0.485, P = 0.006) and between CAT activity and PANSS total scores (r = 0.409, P = 0.022) in TRS male patients. CAT and IL-6 levels were predictors for TRS. Additionally, in chronic schizophrenia patients, a significant positive correlation was observed between IL-6 and GSH-Px (r = 0.292, P = 0.012), and the interaction effect of IL-6 and GSH-Px was positively associated with PANSS general psychopathology scores (r = 0.287, P = 0.014). CONCLUSION: This preliminary study indicated that variations in OS and inflammatory cytokines may be involved in psychopathology for patients with chronic schizophrenia, especially in male patients with TRS.

Chromosome aberrations, micronucleus frequency, and catalase concentration in a population chronically exposed to high levels of radon.

PURPOSE: To deepen our knowledge on the effects of high levels of indoor radon exposure, we assessed the frequencies of unstable and stable chromosome aberrations and micronucleus (MN), as well as the concentration of an endogenous antioxidant (catalase, CAT), in blood samples of individuals chronically exposed to high indoor radon concentrations in Indonesia (Tande-Tande sub-village, Mamuju, West Sulawesi). Moreover, we also investigated the occurrence of a radio-adaptive response (RAR) in Tande-Tande sub-village inhabitants using the G2 MN assay. MATERIALS AND METHODS: The frequencies of dicentric (DC), acentric (AF), ring (R), and translocation (Tr) chromosomes in Tande-Tande inhabitants were compared to those in people living in a reference area with low levels of indoor radon levels (Topoyo village, Indonesia). The number of MN per 1000 binucleated cells (BNC) and CAT concentration per total protein was quantified and compared between groups. Lastly, we irradiated (2 Gy) phytohemagglutinin-stimulated samples in vitro and measured the frequency of MN to verify the occurrence of a RAR in Tande-Tande sub-village inhabitants. RESULTS AND CONCLUSION: The frequencies of DC, AF, and Tr did not differ between Tande-Tande inhabitants and control subjects (p = 0.350, 0.521, 0.597). The frequency of MN in Tande-Tande inhabitants was significantly lower than that in the control group (p = 0.006). Similarly, CAT concentration in Tande-Tande inhabitants was also significantly lower than that in the control population (p < 0.001). Significant negative correlations were identified for MN number and CAT concentration versus indoor radon concentration, annual effective dose, or cumulative dose both within groups and when all data were analyzed together. Our findings indicate that, despite the high indoor radon levels, Tande-Tande inhabitants are not under oxidative stress, since this group had lower CAT concentration and MN frequency than those in the control group. The negative correlation between MN frequency and indoor radon concentration, annual effective dose, and cumulative dose suggests the occurrence of an RAR phenomenon in Tande-Tande sub-village inhabitants. This interpretation is also supported by the results of the G2 MN assay, which revealed lower MN frequencies after in vitro irradiation of samples from Tande-Tande sub-village inhabitants than those in samples from the control group (p = 0.0069, for cumulative MN frequency; p = 0.0146, for radiation-induced MN only).

Effect of Normobaric Hypoxia on Alterations in Redox Homeostasis, Nitrosative Stress, Inflammation, and Lysosomal Function following Acute Physical Exercise.

Hypoxia is a recognized inducer of oxidative stress during prolonged physical activity. Nevertheless, previous studies have not systematically examined the effects of normoxia and hypoxia during acute physical exercise. The study is aimed at evaluating the relationship between enzymatic and nonenzymatic antioxidant barrier, total antioxidant/oxidant status, oxidative and nitrosative damage, inflammation, and lysosomal function in different acute exercise protocols under normoxia and hypoxia. Fifteen competitive athletes were recruited for the study. They were subjected to two types of acute cycling exercise with different intensities and durations: graded exercise until exhaustion (GE) and simulated 30 km individual time trial (TT). Both exercise protocols were performed under normoxic and hypoxic (FiO2 = 16.5%) conditions. The number of subjects was determined based on our previous experiment, assuming the test power = 0.8 and α = 0.05. We demonstrated enhanced enzymatic antioxidant systems during hypoxic exercise (GE: ↑ catalase (CAT), ↑ superoxide dismutase; TT: ↑ CAT) with a concomitant decrease in plasma reduced glutathione. In athletes exercising in hypoxia, redox status was shifted in favor of oxidation reactions (GE: ↑ total oxidant status, ↓ redox ratio), leading to increased oxidation/nitration of proteins (GE: ↑ advanced oxidation protein products (AOPP), ↑ ischemia-modified albumin, ↑ 3-nitrotyrosine, ↑ S-nitrosothiols; TT: ↑ AOPP) and lipids (GE: ↑ malondialdehyde). Concentrations of nitric oxide and its metabolites (peroxynitrite) were significantly higher in the plasma of hypoxic exercisers with an associated increase in inflammatory mediators (GE: ↑ myeloperoxidase, ↑ tumor necrosis factor-alpha) and lysosomal exoglycosidase activity (GE: ↑ N-acetyl-ß-hexosaminidase, ↑ ß-glucuronidase). Our study indicates that even a single intensive exercise session disrupts the antioxidant barrier and leads to increased oxidative and nitrosative damage at the systemic level. High-intensity exercise until exhaustion (GE) alters redox homeostasis more than the less intense exercise (TT, near the anaerobic threshold) of longer duration (20.2 ± 1.9 min vs. 61.1 ± 5.4 min-normoxia; 18.0 ± 1.9 min vs. 63.7 ± 3.0 min-hypoxia), while hypoxia significantly exacerbates oxidative stress, inflammation, and lysosomal dysfunction in athletic subjects.

Ginseng alleviates folliculogenesis disorders via induction of cell proliferation and downregulation of apoptotic markers in nicotine-treated mice.

BACKGROUND: Ginseng is a powerful phytoestrogen with high antioxidant properties. OBJECTIVE: This study aimed to evaluate the effect of Panax Ginseng (PG) on folliculogenesis, proliferation, and apoptosis in the ovary impaired by nicotine. METHODS: Forty adult mice were divided into five groups. Control, sham, and nicotine groups, and co-treated groups of nicotine and ginseng in doses of 0.5 and 1 g/kg. Folliculogenesis was assessed via histopathology and serum evaluation of estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) by ELISA. Lipid peroxidation and antioxidant enzyme activities both in homogenate tissue and serum were assayed by colorimetric analysis. Apoptotic markers of cytochrome c (Cyt c), Bax, and Bcl-2 were evaluated by RT-PCR. Proliferative index was studied by the Ki-67 immunostaining procedure. RESULTS: In comparison to the control or sham groups, nicotine significantly reduced the levels of FSH, LH, and estradiol hormones. An insignificant reduction was observed in the progesterone hormone. Nicotine reduced all healthy follicle numbers, except primordial (P = 0.001). Malondialdehyde (MDA) was increased in tissue and serum in the nicotine group (P = 0.01). Serum catalase (CAT) and enzymatic activity of superoxide dismutase (SOD) both were reduced in tissue and the serum, in the nicotine group. Nicotine induced a reduction in the proliferative indexes of granulosa and theca cells in pre-antral and antral follicles (P = 0.001). However, its effect on the proliferative index of stroma cells was not significant. Apoptotic markers were elevated in the nicotine group (P = 0.001). Co-treatment with ginseng elevated all sex hormones, increased healthy follicles, and reduced tissue or serum lipid peroxidation, compared with the nicotine group (p < 0.05). Co-Treatment with ginseng also reduced the expression of apoptotic markers and increased the proliferative indexes in granulosa and theca cells in pre-antral and antral follicles and also in stroma cells, in comparison to the nicotine group (P = 0.001). All above-mentioned alterations following treatment with ginseng were remarkable, especially in the dose of 1 g/kg. CONCLUSION: This study showed ginseng protects folliculogenesis via alteration of hypothalamic- pituitary-gonadal (HPG) axis, induction of proliferation in ovarian somatic cells, reduction of lipid peroxidation, and downregulation of apoptotic markers in the mouse ovary, treated with nicotine.

Voluntary Exercise Attenuates Hyperhomocysteinemia, But Does not Protect Against Hyperhomocysteinemia-Induced Testicular and Epididymal Disturbances.

The hyperhomocysteinemia (HHcy) is toxic to the cells and associated with several diseases. Clinical studies have shown changes in plasma concentrations of Hcy after physical exercise. This study aimed to assess the effect of HHcy on testis, epididymis and sperm quality and to investigate whether voluntary exercise training protects this system against damage caused by HHcy in Swiss mice. In this study, 48 mice were randomly distributed in the control, HHcy, physical exercise, and HHcy combined with physical exercise groups. HHcy was induced by daily administration of dl-homocysteine thiolactone via gavage throughout the experimental period. Physical exercise was performed through voluntary running on the exercise wheels. The plasma concentrations of homocysteine (Hcy) and testosterone were determined. The testes and epididymis were used to assess the sperm count, histopathology, lipoperoxidation, cytokine levels, testicular cholesterol, myeloperoxidase, and catalase activity. Spermatozoa were analyzed for morphology, acrosome integrity, mitochondrial activity, and motility. In the testes, HHcy increased the number of abnormal seminiferous tubules, reduced the tubular diameter and the height of the germinal epithelium. In the epididymis, there was tissue remodeling in the head region. Ultimately, voluntary physical exercise training reduced plasma Hcy concentration but did not attenuate HHcy-induced testicular and epididymal disturbances.

Vitamin D3 supplementation alleviates chemically-induced cirrhosis-associated hepatocarcinogenesis.

Vitamin D3 (VD3) deficiency has been associated with increased risk for cirrhosis and hepatocellular carcinoma, a highly incident malignant neoplasia worldwide. On the other hand, VD3 supplementation has shown some beneficial effects in clinical studies and rodent models of chronic liver disease. However, preventive effects of dietary VD3 supplementation in cirrhosis-associated hepatocarcinogenesis is still unknow. To investigate this purpose, male Wistar rats submitted to a combined diethylnitrosamine- and thioacetamide-induced model were concomitantly supplemented with VD3 (5,000 and 10,000 IU/kg diet) for 25 weeks. Liver samples were collected for histological, biochemical and molecular analysis. Serum samples were used to measure 25-hydroxyvitamin D [25(OH)D] and alanine aminotransferase levels. Both VD3 interventions decreased hepatic collagen deposition and pro-inflammatory p65 protein levels, while increased hepatic antioxidant catalase and glutathione peroxidase activities and serum 25(OH)D, without a clear dose-response effect. Nonetheless, only the highest concentration of VD3 increased hepatic protein levels of VD receptor, while decreased the number of large preneoplastic glutathione-S-transferase- (>0.5 mm²) and keratin 8/18-positive lesions, as well the multiplicity of hepatocellular adenomas. Moreover, this intervention increased hepatic antioxidant Nrf2 protein levels and glutathione-S-transferase activity. In summary, dietary VD3 supplementation - in special the highest intervention - showed antifibrotic and antineoplastic properties in chemically-induced cirrhosis-associated hepatocarcinogenesis. The positive modulation of Nrf2 antioxidant axis may be mechanistically involved with these beneficial effects, and may guide future clinical studies.

Total antioxidant capacity as a marker of severity of COVID-19 infection: Possible prognostic and therapeutic clinical application.

The pathogenesis of SARS-CoV-2 infection, causative pathogen of the known COVID-19 pandemic is not well clarified. In this regard oxidative stress is one of the topics that need to be investigated. Therefore, the present research was performed to explore the relationship between the oxidant/antioxidant system and COVID-19 exacerbation. Sera were collected from 120 patients with COVID-19 infection and 60 healthy volunteers as the control group. The patient group consisted of 60 cases with mild disease and 60 severely ill patients. Serum levels of total antioxidant capacity (TAC) and nitric oxide (NO) as well as serum activities of the two main antioxidant defense enzymes, superoxide dismutase (SOD) and catalase (CAT), were measured. TAC levels were considerably lower in patients compared with healthy individuals (p < 0.05) and also between patients with mild and severe diseases (p < 0.05). A rather decreasing trend was also found in NO concentration as well as SOD and CAT activity, though, the observed differences were not statistically significant (p > 0.05). These findings suggest that COVID-19 patients may be susceptible to depleted total antioxidant capacity. Moreover, showing such variations in blood samples of infected individuals could be considered as a predictive marker of COVID-19 severity.

Astaxanthin Inhibits Diabetes-Triggered Periodontal Destruction, Ameliorates Oxidative Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant System.

Numerous studies highlight that astaxanthin (ASTX) ameliorates hyperglycemic condition and hyperglycemia-associated chronic complications. While periodontitis and periodontic tissue degradation are also triggered under chronic hyperglycemia, the roles of ASTX on diabetes-associated periodontal destruction and the related mechanisms therein are not yet fully understood. Here, we explored the impacts of supplemental ASTX on periodontal destruction and systemic complications in type I diabetic mice. To induce diabetes, C57BL/6 mice received a single intraperitoneal injection of streptozotocin (STZ; 150 mg/kg), and the hyperglycemic mice were orally administered with ASTX (12.5 mg/kg) (STZ+ASTX group) or vehicle only (STZ group) daily for 60 days. Supplemental ASTX did not improve hyperglycemic condition, but ameliorated excessive water and feed consumptions and lethality in STZ-induced diabetic mice. Compared with the non-diabetic and STZ+ASTX groups, the STZ group exhibited severe periodontal destruction. Oral gavage with ASTX inhibited osteoclastic formation and the expression of receptor activator of nuclear factor (NF)-κB ligand, 8-OHdG, γ-H2AX, cyclooxygenase 2, and interleukin-1ß in the periodontium of STZ-injected mice. Supplemental ASTX not only increased the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and osteogenic transcription factors in the periodontium, but also recovered circulating lymphocytes and endogenous antioxidant enzyme activity in the blood of STZ-injected mice. Furthermore, the addition of ASTX blocked advanced glycation end products-induced oxidative stress and growth inhibition in human-derived periodontal ligament cells by upregulating the Nrf2 pathway. Together, our results suggest that ASTX does not directly improve hyperglycemia, but ameliorates hyperglycemia-triggered periodontal destruction and oxidative systemic complications in type I diabetes.

Effect of Lactobacillus fermentum HFY03 on the Antifatigue and Antioxidation Ability of Running Exhausted Mice.

Yak yogurt is mainly produced in Qinghai-Tibet Plateau. It is a kind of naturally fermented dairy product. It contains abundant microorganisms. Lactobacillus fermentum (LF) HFY03 is a lactic acid bacteria derived from it. Our main research content is to study the influence of LF-HFY03 on the antifatigue and antioxidation ability of running exhausted mice. We gave different doses of LF-HFY03 to mice by gavage for 4 weeks. We selected vitamin C as the positive control group, mainly to study the relationship between antioxidant capacity and fatigue resistance and LF-HFY03 in mice with running exhaustion. The results showed that LF-HFY03 and vitamin C could significantly improve the running time of mice. And with the increase in LF-HFY03 concentration, the exhaustion time of mice was also extended. LF-HFY03 can reduce the content of urea nitrogen and lactic acid and also can increase the content of free fatty acids and liver glycogen. The levels of alanine aminotransferase, serum creatine kinase, and aspartate aminotransferase in mice decreased gradually as the antioxidant peptide level of walnut albumin increased. LF-HFY03 can reduce malondialdehyde (MDA) levels in a quantification-dependent manner and can also increase catalase (CAT) and superoxide dismutase (SOD) levels. LF-HFY03 can also increase the expressions of CAT mRNA, Cu/Zn-SOD, and Mn-SOD in the liver of mice. At the same time, LF-HFY03 can also increase the expression of protein of threonine transporter 1 (AST1)/alanine/cysteine/serine, mRNA, nNOS, and eNOS. At the same time, the solution could reduce the expression of TNF-α, syncytin-1, and inducible nitric oxide synthase (iNOS). The results showed that LF-HFY03 has a high development and application prospect as an antifatigue probiotic nutritional supplement.

Early (5-Day) Onset of Diabetes Mellitus Causes Degeneration of Photoreceptor Cells, Overexpression of Incretins, and Increased Cellular Bioenergetics in Rat Retina.

The effects of early (5-day) onset of diabetes mellitus (DM) on retina ultrastructure and cellular bioenergetics were examined. The retinas of streptozotocin-induced diabetic rats were compared to those of non-diabetic rats using light and transmission electron microscopy. Tissue localization of glucagon-like-peptide-1 (GLP-1), exendin-4 (EXE-4), and catalase (CAT) in non-diabetic and diabetic rat retinas was conducted using immunohistochemistry, while the retinal and plasma concentration of GLP-1, EXE-4, and CAT were measured with ELISA. Lipid profiles and kidney and liver function markers were measured from the blood of non-diabetic and diabetic rats with an automated biochemical analyzer. Oxygen consumption was monitored using a phosphorescence analyzer, and the adenosine triphosphate (ATP) level was determined using the Enliten ATP assay kit. Blood glucose and cholesterol levels were significantly higher in diabetic rats compared to control. The number of degenerated photoreceptor cells was significantly higher in the diabetic rat retina. Tissue levels of EXE-4, GLP-1 and CAT were significantly (p = 0.002) higher in diabetic rat retina compared to non-diabetic controls. Retinal cellular respiration was 50% higher (p = 0.004) in diabetic (0.53 ± 0.16 µM O2 min-1 mg-1, n = 10) than in non-diabetic rats (0.35 ± 0.07 µM O2 min-1 mg-1, n = 11). Retinal cellular ATP was 76% higher (p = 0.077) in diabetic (205 ± 113 pmol mg-1, n = 10) than in non-diabetic rats (116 ± 99 pmol mg-1, n = 12). Thus, acute (5-day) or early onslaught of diabetes-induced hyperglycemia increased incretins and antioxidant levels and oxidative phosphorylation. All of these events could transiently preserve retinal function during the early phase of the progression of diabetes.

Investigation of oxidative stress status in cumulus cells in patients with in vitro fertilization

Background/aim: The negative impact of oxidative stress on oocytes obtained from in vitro fertilization (IVF) patients is a challenge for the optimization of live birth rates. In this study, it is aimed to investigate whether oxidant/antioxidant parameters have a predictive value in terms of determining the count and quality of oocytes. Materials and methods: Catalase (CAT), glutathione-S-transferase (GST), arylesterase (ARE) enzyme activities, and malondialdehyde (MDA) levels were analysed in cumulus cells of poor responder (n = 28, oocyte count ≤ 4), normo responder (n = 48, 5 ≤ oocyte count ≤ 14), and high responder (n = 26, oocyte count ≥ 15) patient groups continuing IVF treatment. Results: The cumulus cell GST enzyme activity were statistically significantly increased in the high responders group compared to the poor responder and the normo responder's groups (p < 0.001 and p = 0.002, respectively). The cumulus cell MDA levels were significantly decreased in the high responder group compared to the poor responder group (p = 0.008). The cumulus cell CAT (p = 0.175) and ARE (p = 0.124) enzyme activities were examined but no statistically significant difference found between the groups. Conclusion: The significant increase in GST enzyme activity and significant decrease in MDA levels in the high responder group indicate that oxidative stress has an effect oocyte status and quality.

Improvement in Redox Homeostasis after Cytoreductive Surgery in Colorectal Adenocarcinoma.

Colorectal cancer (CRC) as one the most common cancer type is associated with oxidative stress. Surgery is the only curative modality for early-stage CRC. The aim of this study was to evaluate the oxidative damage biomarkers as well as enzymatic and nonenzymatic antioxidants in patients with CRC before and after tumor resection and in healthy controls. 60 patients with stage I/II colorectal adenocarcinoma and 43 healthy controls were recruited in this study. We measured plasma levels of oxidative damage biomarkers, including advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), malondialdehyde (MDA), and oxidized low-density lipoprotein (ox-LDL) at baseline and after tumor removal. We also evaluated the plasma activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as enzymatic antioxidants and the ferric reducing antioxidant power (FRAP) assay for nonenzymatic antioxidant capacity. Patients with CRC had significantly higher AGE, AOPP, MDA, and ox-LDL and also FRAP levels and higher SOD and GPx and lower CAT activity levels compared to healthy controls (p < 0.05). We did not observe any statistically significant correlation between redox biomarkers and the size and stage of the tumor. AGEs (72.49 ± 4.7 vs. 67.93 ± 8.8, p < 0.001), AOPP (137.64 ± 21.9 vs. 119.08 ± 33.1, p < 0.001), MDA (3.56 ± 0.30 vs. 3.05 ± 0.33, p < 0.001), and ox-LDL (19.78 ± 0.97 vs. 16.94 ± 1.02, p < 0.001) concentrations reduced significantly after tumor removal. The largest effect sizes were found in ox-LDL (d = -2.853, 95% CI 2.50-3.19) and MDA (d = -1.617, 95% CI 0.43-0.57). Serum FRAP levels (1097.5 ± 156.7 vs. 1239.3 ± 290, p < 0.001) and CAT (2.34 ± 0.34 vs. 2.63 ± 0.38, p < 0.001), GPx (102.37 ± 6.58 vs. 108.03 ± 6.95, p < 0.001), and SOD (5.13 ± 0.39 vs. 5.53 ± 0.31, p < 0.001) activity levels increased significantly after surgery. The largest effect sizes among antioxidants were seen in SOD (d = 1.135, 95% CI 0.46-0.34) and GPx (d = 0.836, 95% CI 0.35-0.23). This study indicated that patients with colorectal cancer had higher levels of oxidative stress and antioxidant activity compared to healthy controls. After surgical resection of tumor, we observed a substantial improvement in redox homeostasis.

Prophylactic effect of myricetin and apigenin against lipopolysaccharide-induced acute liver injury.

BACKGROUND: Liver has an important role in the initiation and progression of multiple organ failure that occurs in sepsis. Many natural active substances can be used to reduce the liver injury caused by sepsis. For this aim, the effects of myricetin and apigenin on mice model of acute liver injury was evaluated in this study. METHODS AND RESULTS: Thirty-six mice were randomly divided into six groups as; control, lipopolysaccharide (LPS) (5 mg/kg), LPS + myricetin (100 mg/kg), LPS + myricetin (200 mg/kg), LPS + apigenin (100 mg/kg), and LPS + apigenin (200 mg/kg) groups. Myricetin and apigenin were administered orally for 7 days, and LPS was administered intraperitoneally only on the 7th day of the study. 24 h after LPS application, all animals were sacrificed and serum biochemical parameters, histopathology and oxidative stress and inflammation markers of liver tissue were examined. Myricetin and apigenin pre-treatments increased serum albumin and total protein levels, liver GSH level and catalase and SOD activities and decreased serum ALT, AST, ALP, γ-GT, CRP, total and direct bilirubin levels, liver MPO activity, MDA, NOx, PGE2, TNF-α, IL-1ß, and IL-6 levels, iNOS and COX-2 mRNA levels, phosphorylation of NF-κB p65, IκB, and IKK proteins but not p38, ERK, and JNK proteins in LPS-treated mice. Myricetin and apigenin administration also regained the hepatic architecture disrupted during LPS application. CONCLUSION: Myricetin and apigenin pre-treatments led to reduction of liver injury indices and oxidative stress and inflammatory events and these flavonoids has probably hepatoprotective effects in acute liver injury.

Wild garlic extract reduces lipid peroxidation in terbuthylazine-treated human erythrocytes.

Background: Among other negative effects, herbicides induce oxidative stress, leading to lipid peroxidation and protein oxidation. Therefore, there is a growing need to identify natural compounds with sufficient antioxidant capacity and mitigate the negative effects of herbicides without side effects.Objective: Our study aimed to examine the protective effect of the phenolic extract of wild garlic (WG) leaves on terbuthylazine-treated erythrocytes.Material and methods: In human erythrocytes treated with the herbicide terbuthylazine (4.5 mg/L) alone and a combination of terbuthylazine and WG extract, we measured malondialdehyde (MDA) and haemoglobin (Hb) concentrations and the antioxidant activities of CuZn superoxide dismutase (SOD1; EC 1.15.1.1) and catalase (CAT; EC 1.11.1.6) in vitro.Results: In comparison with terbuthylazine, WG extract reduced the concentrations of MDA and Hb from 59.69 to 43.45 nmol/gHb (27%, p < 0.001) and 165.08 to 128.64 g/L (22%, p < 0.05), respectively. Catalase activity was induced for samples treated with both WG extract and terbuthylazine compared with terbuthylazine alone (p < 0.05).Conclusions: The results demonstrated that WG may reduce the toxicity of terbuthylazine, and the erythrocyte membrane may be the primary site of phenolic action. Therefore, the lipid peroxidation intensity could be a biomarker of oxidative damage caused by terbuthylazine and the protective effect of WG.

Redox State and Lysosomal Activity in Women with Ovarian Cancer with Tumor Recurrence and Multiorgan Metastasis.

The aim of the study is to evaluate oxidant-antioxidant balance as well as lysosomal and anti-protease activities in ovarian cancer since it has been emphasized that the crucial inducing factor of carcinogenesis may be reactive oxygen/nitrogen species or, more precisely, oxidative stress-induced inflammation. The study involved 15 women with ovarian cancer, aged 59.9 ± 7.8 years, and 9 healthy women aged 56.3 ± 4.3 years (controls). The study material was venous blood collected from fasting subjects. In erythrocytes, the activities of superoxide dismutase, glutathione peroxidase, and catalase, as well as concentrations of conjugated dienes (CDs) and thiobarbituric acid reactive substances (TBARS), were investigated. CD, TBARS, and vitamins A and E plasma concentrations were also determined. Moreover, total antioxidant capacity and concentrations of 4-hydroxynonenal adducts and 8-iso-prostaglandin F2α, as well as activities of acid phosphatase, arylsulfatase, cathepsin D, and α1-antitrypsin, were studied in serum. The vitamin E and 8-iso-prostaglandin F2α concentrations as well as arylsulfatase activity were lower in the women with cancer compared to the controls (p = 0.006, p = 0.03, p = 0.001, respectively). In contrast, cathepsin D activity was lower in the controls (p = 0.04). In the peripheral blood of the women with cancer, oxidant-antioxidant and lysosomal disturbances were observed.

Ameliorative effects of fisetin in letrozole-induced rat model of polycystic ovary syndrome.

BACKGROUND: The present study was conducted to investigate the therapeutic effects of a potent polyphenol, fisetin, on the letrozole-induced rat model of polycystic ovary syndrome (PCOS). METHODOLOGY: Twenty-four female Wistar rats (42 days old) were divided into four groups: control group (received carboxy methylcellulose (CMC 0.5 %)), PCOS group treated with letrozole (1 mg/kg), fisetin group received same dose of letrozole + fisetin (10 mg/kg), and metformin group received same dose of letrozole + metformin (300 mg/kg). At the end of the experiment, biochemical (glucose, lipid profile) and hormonal (insulin, testosterone, estradiol, and progesterone) parameters were analyzed. Histological examinations of ovaries were also conducted by hematoxylin and eosin (H&E) staining. Real-time polymerase chain reaction (PCR) and western blotting were carried out for cytochrome P450 17A1 (CYP17A1), sirtuin-1 (SIRT1), and 5' AMP-activated protein kinase (AMPK) gene expression in the ovaries. Furthermore, enzymatic activities of antioxidants including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the ovaries were analyzed by colorimetric method. RESULTS: Letrozole administration resulted in a remarkable abnormality in biochemical and hormonal parameters. Fisetin normalized levels of glucose, lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), testosterone, estradiol, and progesterone. Moreover, fisetin increased expression levels of SIRT1 and AMPK, and decreased expression level of CYP17A1 in the ovaries. Additionally, fisetin showed protective effect by enhancing antioxidant activities of CAT, SOD, and GPx depleted secondary to induction of PCOS. Fisetin effects were comparable to metformin, as the standard drug used for treatment of PCOS. CONCLUSION: Our results showed that, fisetin treatment caused significant alleviating effects by restoring PCOS-induced alterations in the key genes involved in energy homeostasis and antioxidant enzymes, suggesting that it may have a key role in combating with PCOS.

Analysis of Biomechanical Parameters of Muscle Soleus Contraction and Blood Biochemical Parameters in Rat with Chronic Glyphosate Intoxication and Therapeutic Use of C60 Fullerene.

The widespread use of glyphosate as a herbicide in agriculture can lead to the presence of its residues and metabolites in food for human consumption and thus pose a threat to human health. It has been found that glyphosate reduces energy metabolism in the brain, its amount increases in white muscle fibers. At the same time, the effect of chronic use of glyphosate on the dynamic properties of skeletal muscles remains practically unexplored. The selected biomechanical parameters (the integrated power of muscle contraction, the time of reaching the muscle contraction force its maximum value and the reduction of the force response by 50% and 25% of the initial values during stimulation) of muscle soleus contraction in rats, as well as blood biochemical parameters (the levels of creatinine, creatine phosphokinase, lactate, lactate dehydrogenase, thiobarbituric acid reactive substances, hydrogen peroxide, reduced glutathione and catalase) were analyzed after chronic glyphosate intoxication (oral administration at a dose of 10 µg/kg of animal weight) for 30 days. Water-soluble C60 fullerene, as a poweful antioxidant, was used as a therapeutic nanoagent throughout the entire period of intoxication with the above herbicide (oral administration at doses of 0.5 or 1 mg/kg). The data obtained show that the introduction of C60 fullerene at a dose of 0.5 mg/kg reduces the degree of pathological changes by 40-45%. Increasing the dose of C60 fullerene to 1 mg/kg increases the therapeutic effect by 55-65%, normalizing the studied biomechanical and biochemical parameters. Thus, C60 fullerenes can be effective nanotherapeutics in the treatment of glyphosate-based herbicide poisoning.