Effect Of Antioxidant Therapy Research Articles

The effect of antioxidant therapy on the course of predialysis chronic kidney disease in a patient with comorbidity

Chronic kidney disease (CKD) is almost always associated with comorbidities such as diabetes, hyperuricemia/gout, urolithiasis, often with urinary tract infection, hypertension, polycystic kidney disease, and other conditions. Autosomal dominant polycystic kidney disease is an inherited kidney disease (1/1000–1/400 worldwide) affecting mainly adults, caused predominantly by mutations in PKD1 (85–90 % of cases) and PKD2 genes (10–15 % of cases), which encode polycystin-1 and polycystin-2 proteins, respectively. In adults with preserved kidney function, the prevalence of gout increases from 1 to 2 % (hyperuricemia up to 11 %), in patients with CKD stage 4 — up to 32 % (hyperuricemia up to 80 %). 70 % of patients with gout and 50 % of patients with hyperuricemia have stage 2 CKD. CKD contributes to a decrease in the urinary excretion of uric acid. In patients with CKD, hyperuricemia is considered to be a serum uric acid level > 6 mg/dL in women and > 7 mg/dL in men. Hyperuricemia is very often observed in hypertension and type 2 diabetes. In patients with kidney disease, diabetes is a major factor of mortality and morbidity. Diabetic nephropathy can be suspected in a patient with type 2 diabetes in the presence of albuminuria and/or diabetic retinopathy. Signs of diabetic nephropathy: basement membrane thickening, mesangial expansion, and increased vascular permeability to albumin induced by nonenzymatic glycation of collagen and laminin. Comorbidity has a negative impact on patients’ health due to increased morbidity and mortality. Such patients are at risk of rapid progression of CKD into the end stage, which requires renal replacement therapy. Therefore, early diagnosis, treatment and prevention of CKD complications are important for such patients. This article highlights the impact of antioxidant therapy and phytoneering on the course of CKD in patients with comorbidities.

Evaluation of the index of resistance and excretion of uromodulin in patients with predialysis chronic kidney disease, taking into account the index of comorbidity

Background. The purpose of this study was to investigate urinary uromodulin (uUmod) excretion, reactivity of the autonomic nervous system and impaired renal blood circulation in patients with predialysis chronic kidney disease (CKD), and the effect of antioxidant therapy on these parameters. Materials and methods. Ninety-one patients with CKD stage 1–5 took part in the ROLUNT (UROmoduLin UbiquinoNe GlutaThione) study, their average age was 47.00 ± 12.12 years. Thirty (32.97 %) men and 61 (67.03 %) women were divided into two groups, which were representative in terms of age and gender composition: the first one (n = 46) — patients with CKD stage1–5 who had Charlson Comorbidity Index ≤ 2, the second one (n = 45) — patients with CKD stage1–5 who had Charlson Comorbidity Index ≥ 3. The first and second groups were divided into subgroups A and B. Subgroup A included patients with impaired vegetative status, subgroup B — without impaired vegetative status. Subgroups 1A and 2B took glutathione 100 mg twice a day with food for 3 months; subgroups 1B and 2A received ubiquinone 100 mg once a day with food for 3 months. In patients with CKD stage1–5, uUmod, albumin to creatinine ratio (ACR), glomerular filtration rate (GFR) were evaluated. Ninety-one ultrasound duplex color scans of the kidneys were performed and the index of resistance (IR) was determined in patients with CKD stage1–5. Results. The results of the paired t-test showed that there is a significant difference between the indicators at the beginning and at the end of the study, with the exception of the following: in subgroup 1A: hemoglobin (Hb) (T = –1.5863 [–2.0739, 2.0739] 95% confidence interval (CI) [–2.4077, 0.3207], p = 0.127); in subgroup 1B: Hb (T = –0.382 [–2.0739, 2.0739], 95% CI [–1.3977, 0.963], p = 0.706); ACR (T = –1.5899 [–2.0739, 2.0739], 95% CI [–16.7323, 2.2105], p = 0.126); systolic blood pressure (SBP) (T = –0.5625 [–2.0739, 2.0739], 95% CI [–2.2414, 1.2849], p = 0.579); diastolic blood pressure (DBP) (T = –1.7936 [–2.0739, 2.0739], 95% CI [–2.3437, 0.1698], p = 0.087); Chernov questionnaire (T = 1.5071 [–2.0739, 2.0739], 95% CI [–0.6083, 3.8431], p = 0.146); Kérdö index (T = 0.9392 [–2.0739, 2.0739], 95% CI [–1.1083, 2.9431], p = 0.358); in subgroup 2A: ACR (T = –2.0147 [–2.0796, 2.0796], 95% CI [–39.1946, 0.6219], p = 0.057); in subgroup 2B: ACR (T = –1.3328 [–2.0739, 2.0739], 95% CI [–17.4695, 3.7999], p = 0.196). The Pearson correlation results showed that in subgroup 1A, there is a significant average positive relationship between uUmod and eGFR (r(21) = 0.418, p = 0.047); a significant very small negative relationship between uUmod indicators and age (r(21) = 0.438, p = 0.037); in subgroup 1B, there is a significant large positive relationship between uUmod and Hb indicators (r(21) = 0.513, p = 0.012); a significant positive relationship between uUmod and Morisky Medication Adherence Scale-8 (MMAS-8) indicators (r(21) = 0.515, p = 0.012); a significant very small negative relationship between uUmod and ACR indicators (r(21) = 0.441, p = 0.035); in subgroup 2A, there is a significant very small negative relationship between uUmod indicators and Kérdö index (r(20) = 0.427, p = 0.048); in subgroup 2B, there is a significant very small negative relationship between the uUmod indicators and Chernov questionnaire score (r(21) = 0.421, p = 0.045); a significant very small negative relationship between uUmod indicators and Charlson Comorbidity Index (r(21) = 0.481, p = 0.020); a significant very small negative relationship between uUmod and age (r(21) = 0.471, p = 0.023). In subgroup 1A at the end of the study, the following independent variables are not significant as predictors for uUmod: IRd, IRs, SBP, DBP, Hb, ACR, age, Vein and Chernov questionnaires score, MMAS-8, Charlson Comorbidity Index and Kérdö index. In subgroup 1B at the end of the study, the following independent variables are not significant as predictors for uUmod: eGFR, IRs, SBP, DBP, Hb, Vein and Chernov questionnaires score, MMAS-8, Charlson Comorbidity Index and Kérdö index. In subgroup 2A at the end of the study, the following independent variables are not significant as predictors for uUmod: eGFR, IRd, IRs, SBP, DBP, Hb, ACR, age, Vein questionnaire score, MMAS-8, Charlson Comorbidity Index. In subgroup 2B at the end of the study, the following independent variables are not significant as predictors for uUmod: eGFR, IRd, IRs, SBP, DBP, Hb, ACR, age, Vein questionnaire score, ­MMAS-8, Kérdö index. Conclusions. Antioxidant therapy with glutathione and ubiquinone significantly affects the examination parameters of patients with CKD. Considering the safety and effectiveness of antioxidant therapy, we suggest including antioxidant therapy into the treatment protocols for patients with CKD. Further research is recommended to establish a standard protocol.

Progress of Research on Antioxidants and Carriers for Skin Wound Repair

The skin is the first protective barrier of the human body, and oxidative damage is one of the main mechanisms of skin injury. Effective antioxidant therapy plays an important role in skin healing. Therefore, exploring antioxidants and suitable drug delivery methods that can be used for skin injury repair is of great value in regulating skin repair and regeneration and promoting wound healing. Based on this, this paper presents a review of the progress of research on (1) antioxidants and (2) antioxidant carriers for skin repair in order to summarize the research results and provide reference for the subsequent development of new drug-carrier structures and new skin repair strategies.

The effect of antioxidant therapy on some pathogenetic factors of primary open-angle glaucoma

The study analyzes the vascular remodulation, antioxidant and antihypoxic effects of the drug Mexidol in patients with PAOG. The study included 78 patients with POAG of the early (n=43) and advanced stage (n=35) with average age of 67.8±1.5 years. The main study group consisted of 47 patients who received Mexidol in addition to local hypotensive treatment; 31 patients comprised the control group. In the comparison groups, the degree of ED was determined by the results of reactive hyperemia test, patients' blood plasma was analyzed for levels of stable nitric oxide metabolite (nitrite NO2-) and endothelin-1 (ET-1). General assessment of oxidative stress was carried out by high-performance liquid chromatography. Functional activity of the retina was studied using an electroretinograph and static computer perimetry performed according to the standard technique. The following changes are observed in patients of the main group using Mexidol: the index of oscillatory potentials significantly increases, peak latency decreases, perimeter indices show positive trends, vascular endothelial function improves according to reactive hyperemia test, concentration of vasoconstrictor mediator ET-1 in blood plasma decreases and of nitrite (NO2-) increases moderately, the coefficient of bioeffective vasotonic activity decreases, the level of glutathione peroxidase increases (p<0.05 compared to the baseline value), the level of malonyldialdehyde decreases, lipid metabolism improves (reduction in total cholesterol, low-density lipoprotein-cholesterol, triglycerides, decrease in the Atherogenic Index compared to the initial level). The drug Mexidol proved to be an effective endothelial protector, a powerful antioxidant and antihypoxant, contributed to deceleration of atherogenesis in patients with POAG.

The role of oxidative stress in neurodegenerative diseases and potential antioxidant therapies.

The central nervous system (CNS) is essential for homeostasis and controls the physiological functions of the body. However, the biochemical characteristics of the CNS make it especially vulnerable to oxidative damage (OS). This phenomenon compromises correct CNS functioning, leading to neurodegeneration and neuronal death. OS plays a crucial role in the physiopathology of neurodegenerative diseases. It is involved in multiple mechanisms of nucleic acid, protein, and lipid oxidation, thereby contributing to progressive brain damage. These mechanisms include mitochondrial dysfunction; excessive production of reactive oxygen and nitrogen species; deficiency of antioxidant defenses; protein oligomerization; cytokine production and inflammatory response; blood-brain barrier abnormalities; and proteasome dysfunction. All these dysfunctions are involved in the pathogenesis ofneurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, or amyotrophic lateral sclerosis. A curative treatment is currently not available. Research is focused on the search for therapies that reduce oxidative damage and delay disease progression. In the recent years, researchers have focused their attention on the effects of antioxidant therapies.

The effect of antioxidant therapy on the chronostructure of the respiratory biorhythm in patients with chronic obstructive pulmonary disease

The article deals with an issue of the day, the effect of antioxidant therapy on the temporal organization of external respiration in patients with chronic obstructive pulmonary disease. Data on diurnal rhythm, circaseptane and circasemiseptane rhythms of external respiration parameters in patients suffering from chronic obstructive pulmonary disease under the influence of antioxidant therapy using Eltacin are represented.

Oxidative Stress in Tauopathies: From Cause to Therapy.

Oxidative stress (OS) is the result of an imbalance between the production of reactive oxygen species (ROS) and the antioxidant capacity of cells. Due to its high oxygen demand, the human brain is highly susceptible to OS and, thus, it is not a surprise that OS has emerged as an essential component of the pathophysiology of several neurodegenerative diseases, including tauopathies. Tauopathies are a heterogeneous group of age-related neurodegenerative disorders characterized by the deposition of abnormal tau protein in the affected neurons. With the worldwide population aging, the prevalence of tauopathies is increasing, but effective therapies have not yet been developed. Since OS seems to play a key role in tauopathies, it has been proposed that the use of antioxidants might be beneficial for tau-related neurodegenerative diseases. Although antioxidant therapies looked promising in preclinical studies performed in cellular and animal models, the antioxidant clinical trials performed in tauopathy patients have been disappointing. To develop effective antioxidant therapies, the molecular mechanisms underlying OS in tauopathies should be completely understood. Here, we review the link between OS and tauopathies, emphasizing the causes of OS in these diseases and the role of OS in tau pathogenesis. We also summarize the antioxidant therapies proposed as a potential treatment for tauopathies and discuss why they have not been completely translated to clinical trials. This review aims to provide an integrated perspective of the role of OS and antioxidant therapies in tauopathies. In doing so, we hope to enable a more comprehensive understanding of OS in tauopathies that will positively impact future studies.

Protective Effect of Salvianolic Acid A against N-Methyl-N-Nitrosourea-Induced Retinal Degeneration.

Objective Retinal degeneration (RD) is a serious, irreversible, and blinding eye disease, which seriously affects the visual function and quality of life of patients. At present, there is no effective method to treat RD. The final outcome of its development is photoreceptor cell oxidation and apoptosis. Therefore, looking for safe, convenient, and effective antioxidant therapy is still the key research field of Rd. In this study, the mice model of RD was induced by N-methyl-N-nitrosourea (MNU) in vivo to explore the therapeutic effect and mechanism of salvianolic acids (Sal A) on RD. In vitro, the protective effect of Sal A on MNU injured 661 W cell line of mouse retina photoreceptor cone cells was investigated preliminarily. Methods Male C57BL/6 mice (7–8 weeks old) received a single intraperitoneal injection (ip) of 60 mg/kg MNU or vehicle control. Treatment groups then received Sal-A 0.5 mg/kg and 1.0 mg/kg via daily intravenous injections. On day 7, functional and morphological examinations were performed, including photopic and scotopic electroretinography (ERG) and hematological analyses to observe functional changes and damage to the outer nuclear layer (ONL). On the 3rd and 7th days, the levels of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were determined. The expression of retinal Bax, Bcl-2, and caspase-3 was quantified by Western blot and RT-PCR assays. 661 W strain of mice retinal photoreceptor cone cells were cultured in vitro and treated with 1 µm MNU. The cells in the treatment group were given 50 μM Sal A as an intervention. The growth of 661 W cells was observed and recorded under an inverted light microscope, and the activity of cells was detected by the MTT method. Results Sal A treatment was effective against MNU-induced RD in mice at both 0.5 mg/kg/d and 1.0 mg/kg/d doses, and the protective effect was dose-dependent. Sal A can alleviate MNU-mediated alterations to retinal ERG activity and can support maintenance of the thickness of the ONL layer. Sal A treatment increases the expression of retinal SOD and reduces the lipid peroxidation product MDA, suggesting that its protective effect is related to the oxidation resistance. It can offset changes to the expression of apoptotic factors in the retina caused by MNU treatment. Sal A mitigates MNU-mediated damage to cultured mice photoreceptor cone cells 661 W in vitro. Conclusion Sal A alleviates the damage caused by MNU to retinal photoreceptor cells in vivo and in vivo, and its protective effect is related to its antioxidant and antiapoptotic activities.

The effectiveness of antioxidant therapy (vitamin C) in an experimentally induced mouse model of ovarian endometriosis.

Objectives:This study investigates the therapeutic effect of vitamin C on the development of endometrial lesions and fecundity disorders in the ovarian induction model of mouse endometriosis.Methods:Ovarian endometriosis was surgically induced in 14 NMRI female mice (treatment group, N = 7) and (control group, N = 7). Three days after the second surgery (to assess endometriotic implant), the mice were randomized into two intervention groups: control (placebo) and treatment (50 mg/kg vitamin C every two days orally for four weeks) groups. In the oestrus phase, the mice were sacrificed. In macroscopic assessment, endometriotic implants were evaluated in size, volume, weight, growth score and adhesion score. The microscopic assessment examined the ovarian tissue (the number of antral follicles, corpus luteum and atretic follicles) and endometriotic lesion (histologic and trichrome fibrosis scores).Results:Post-treatment implant volume, growth score, adhesion extent score and adhesion severity score were significantly lower in the treatment group (vitamin C) in comparison with the control group (placebo) (p < 0.0001). The difference between the median weight of endometriotic implants, epithelialization of implant tissue, trichrome fibrosis scores and follicle number in the two groups (treatment and control) was statistically significant (p < 0.05). Atretic follicles were significantly decreased after vitamin C therapy (p < 0.05). Although the numbers of corpus luteum seemed to be more preserved in specimens from the control group, there was no statistical significance between the two groups’ histological scores.Conclusion:As a result, we may imply that vitamin C has a significant effect on reducing the induction and growth of endometrial implants, improving the fecundity function of ovaries, and consequently prevention of endometriosis-associated cancers. Further research is needed to improve targeted interventions resulting in the prevention and treatment of human endometriosis.

Genome-wide mRNA profiling identifies the NRF2-regulated lymphocyte oxidative stress status in patients with silicosis

BackgroundThe immunomodulatory abnormalities of silicosis are related to the lymphocyte oxidative stress state. The potential effect of antioxidant therapy on silicosis may depend on the variation in nuclear factor erythroid 2-related factor 2 (NRF2)-regulated antioxidant genes in peripheral blood mononuclear cells (PBMCs). As NRF2 is a redox-sensitive transcription factor, its possible roles and underlying mechanism in the treatment of silicosis need to be clarified.MethodsNinety-two male patients with silicosis and 87 male healthy volunteers were randomly selected. PBMCs were isolated from fresh blood from patients with silicosis and healthy controls. The lymphocyte oxidative stress state was investigated by evaluating NRF2 expression and NRF2-dependent antioxidative genes in PBMCs from patients with silicosis. Key differentially expressed genes (DEGs) and signaling pathways were identified utilizing RNA sequencing (RNA-Seq) and bioinformatics technology. Gene set enrichment analysis was used to identify the differences in NRF2 signaling networks between patients with silicosis and healthy controls.ResultsThe number of monocytes was significantly higher in patients with silicosis than that of healthy controls. Furthermore, RNA-Seq findings were confirmed using quantitative polymerase chain reaction and revealed that NRF2-regulated DEGs were associated with glutathione metabolism, transforming growth factor-β, and the extracellular matrix receptor interaction signaling pathway in PBMCs from patients with silicosis. The top 10 hub genes were identified by PPI analysis: SMAD2, MAPK3, THBS1, SMAD3, ITGB3, integrin alpha-V (ITGAV), von Willebrand factor (VWF), BMP4, CD44, and SMAD7.ConclusionsThese findings suggest that NRF2 signaling regulates the lymphocyte oxidative stress state and may contribute to fibrogenic responses in human PBMCs. Therefore, NRF2 might serve as a novel preventive and therapeutic candidate for silicosis.

Men's Reproductive Health: Oxidative Stress and the Effectiveness of Antioxidant Therapy

This review article surveys and summarizes the literature data concerning the problems of deterioration of the main indicators of men's reproductive health and the effectiveness of therapy with drugs with antioxidant properties. The analysis of domestic and foreign literature confirms that oxidative stress (OS) accompanies and/or is one of the pathogenetic links in the development of many types of reproductive pathology in men. The health status of the male population is influenced by the following factors: lifestyle, existing diseases, the state of the environment, and the genotype of the population. The interaction of several weak, but unidirectional, factors creates a high risk of developing male reproductive pathology. The polyetiological nature of fertility disorders in men causes certain difficulties in creating adequate methods of treating this pathology and causes multicomponent biocomplexes to appear on the pharmaceutical market that contain active substances that can affect the quality of the ejaculate.

Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease

Among all the proposed pathogenic mechanisms to understand the etiology of Alzheimer’s disease (AD), increased oxidative stress seems to be a robust and early disease feature where many of those hypotheses converge. However, despite the significant lines of evidence accumulated, an effective diagnosis and treatment of AD are not yet available. This limitation might be partially explained by the use of cellular and animal models that recapitulate partial aspects of the disease and do not account for the particular biology of patients. As such, cultures of patient-derived cells of peripheral origin may provide a convenient solution for this problem. Peripheral cells of neuronal lineage such as olfactory neuronal precursors (ONPs) can be easily cultured through non-invasive isolation, reproducing AD-related oxidative stress. Interestingly, the autofluorescence of key metabolic cofactors such as reduced nicotinamide adenine dinucleotide (NADH) can be highly correlated with the oxidative state and antioxidant capacity of cells in a non-destructive and label-free manner. In particular, imaging NADH through fluorescence lifetime imaging microscopy (FLIM) has greatly improved the sensitivity in detecting oxidative shifts with minimal intervention to cell physiology. Here, we discuss the translational potential of analyzing patient-derived ONPs non-invasively isolated through NADH FLIM to reveal AD-related oxidative stress. We believe this approach may potentially accelerate the discovery of effective antioxidant therapies and contribute to early diagnosis and personalized monitoring of this devastating disease.

N-acetylcysteine, xCT and suppression of Maxi-chloride channel activity in human placenta

IntroductionPlacental oxidative stress features in pregnancy pathologies but in clinical trials antioxidant supplementation has not improved outcomes. N-acetylcysteine (NAC) stimulates glutathione production and is proposed as a therapeutic agent in pregnancy. However, key elements of N-acetylcysteine biology, including its cellular uptake mechanism, remains unclear. This study explores how the cystine/glutamate transporter xCT may mediate N-acetylcysteine uptake and how N-acetylcysteine alters placental redox status. MethodsThe involvement of xCT in NAC uptake by the human placenta was studied in perfused placenta and Xenopus oocytes. The effect of short-term N-acetylcysteine exposure on the placental villous proteome was determined using LC-MS. The effect of N-acetylcysteine on Maxi-chloride channel activity was investigated in perfused placenta, villous fragments and cell culture. ResultsMaternoplacental N-acetylcysteine administration stimulated intracellular glutamate efflux suggesting a role of the exchange transporter xCT, which was localised to the microvillous membrane of the placental syncytiotrophoblast. Placental exposure to a bolus of N-acetylcysteine inhibited subsequent activation of the redox sensitive Maxi-chloride channel independently of glutathione synthesis. Stable isotope quantitative proteomics of placental villi treated with N-acetylcysteine demonstrated changes in pathways associated with oxidative stress, apoptosis and the acute phase response. DiscussionThis study suggests that xCT mediates N-acetylcysteine uptake into the placenta and that N-acetylcysteine treatment of placental tissue alters the placental proteome while regulating the redox sensitive Maxi-chloride channel. Interestingly N-acetylcysteine had antioxidant effects independent of the glutathione pathway. Effective placental antioxidant therapy in pregnancy may require maintaining the balance between normalising redox status without inhibiting physiological redox signalling.

The effect of the duration of treatment with antioxidants on age-related hearing loss

Background and aims The effect of antioxidants depends on several factors, including the type, dose, timing, and treatment duration. Several studies have demonstrated that antioxidants can prevent age-related hearing loss (ARHL), however, a few studies have focussed on the role of factors influencing the effects of antioxidant therapy. This study aimed to investigate the effect of duration of treatment on ARHL using an herbal antioxidant, silymarin, in a D-galactose-induced ageing rat model. Method 40 three-months-old Wistar rats were divided into four groups: a short-term silymarin-treated group that received 500 mg/kg/day D-galactose (8 consecutive weeks) +200 mg/kg/day silymarin (4 consecutive weeks), long-term silymarin-treated group received 500 mg/kg/day D-galactose (8 consecutive weeks)+ 200 mg/kg/day silymarin (8 consecutive weeks), placebo group received 500 mg/kg/day D-galactose + placebo (propylene glycol; 8 consecutive weeks), and control group received normal saline (8 consecutive weeks). Auditory Brainstem Response (ABR) was measured at 4, 8, 12, and 16 kHz frequencies before and after the intervention. Results No significant differences were found in ABR absolute and inter-peak latencies between groups. In contrast, there was a significant difference in ABR threshold shift between the placebo and the long-term silymarin-treated groups at 4 and 16 kHz frequencies (p ≤ .05), but without a similar difference through comparison with the short-term silymarin-treated group (p > .05). Additionally, a significant decrease in ABR amplitude of PI and PII was observed in the placebo group at 4 kHz frequency compared to the long-term silymarin-treated group (p ≤ .05), but not to the short-term silymarin-treated group (p > .05). Conclusion The present study results indicate that the duration of treatment with antioxidants influences the successful prevention and treatment of ARHL. Consequently, this factor must be considered in the antioxidant therapy of ARHL. However, further studies are required to fully evaluate the effects of optimal treatment duration with antioxidants on ARHL along with the other influencing factors.

Effect of antioxidant therapy on arrhythmia in patients with acute myocardial infarction after percutaneous transluminal coronary intervention

Effect of antioxidant therapy on arrhythmia in patients with acute myocardial infarction after percutaneous transluminal coronary intervention

Современный взгляд на применение антиоксидантов в терапии мужского бесплодия

Based on the literature data, this review discusses the prevalence and etiology of male infertility, as well as the current view of the reasons for the lack of effectiveness of treatment of idiopathic infertility in men. The effectiveness of antioxidant therapy in various variants of redox balance disorders is evaluated. Possible prerequisites and mechanisms of complications in the administration of antioxidants are described. In addition, the need to introduce laboratory confirmation of oxidative stress and review approaches to antioxidant therapy is justified. The article also discusses the possibility of treating idiopathic pathospermia with the help of a complex drug Androdoz, which, according to the literature, can improve such indicators of sperm as the volume of ejaculate, the number and viability of spermatozoa and the proportion of their actively mobile forms due to the synergy of its components.

Posibilidades de la terapia antioxidante en diabetes mellitus tipo 2. Estudio del estrés oxidativo en una muestra poblacional de pacientes diabéticos

Introducción: el organismo se expone cotidianamente a diferentes agentes que provocan reacciones oxidativas normalmente controladas. La sobreproducción de especies reactivas del oxígeno y/o la deficiencia de antioxidantes lleva al estrés oxidativo (EO) asociado a patologías crónicas que contribuye a un peor pronóstico de las enfermedades. Una de esas patologías crónicas es la diabetes mellitus (DM), en la que se ha demostrado una gran participación del EO en su fisiopatología y en el desarrollo de complicaciones. Se determinó el índice de EO (IEO) en individuos con DM y en un grupo sano control, para evaluar su posible correlación y grado de daño oxidativo, como estrategia para justificar una intervención potencial con una terapia antioxidante adyuvante al tratamiento convencional.&#x0D; Materiales y métodos: se midió IEO en una población de 110 individuos con DM, constituida por 37 casos de DM tipo 1 (DMT1) y 73 del tipo 2 (DMT2) en edades entre 50 y 70 años escogidos al azar y se comparó con los valores de un grupo control de voluntarios sanos. El objetivo del ensayo clínico fue definir el grado de correlación entre los niveles del IEO y la severidad del daño oxidativo, ponderado a partir de una fórmula cualitativa, a través de la medición de nueve biomarcadores del EO en lisados de eritrocitos.&#x0D; Discusión: la prevención o la detención de las comorbilidades de la DM puede que descanse en el futuro en la identificación precisa de los biomarcadores y su contrapartida reguladora. La incorporación de una terapia utilizando un protocolo con antioxidantes (AO) adyuvantes al manejo estándar de la DMT2 podría proveer resultados más eficaces para el control hiperglucémico y, por tanto, para inducir el equilibrio redox. Los resultados demuestran que ese tipo de terapia no sería eficaz en DMT1. Es determinante el reconocimiento de la extensión y tipo de daño oxidativo de las poblaciones específicas, mediante la creación y utilización de una línea de base con los biomarcadores alterados más frecuentemente. Esta línea de base ayudará a definir la mejor estrategia antioxidante a aplicar, porque el polimorfismo genético, el ambiente y los hábitos de vida actúan puntualmente en el tipo respuesta al EO. Una estrategia beneficiosa a valorar puede ser la del desarrollo de nuevos fármacos con efectos antioxidantes o de productos capaces de reforzar el sistema fisiológico de antioxidación a partir de sustratos naturales y la elaboración de combinaciones de dosis fijas de AO eficaces que ataquen las causas el EO en la DM. El objetivo final será el de revertir el daño oxidativo para prevenir la instalación de complicaciones o frenarlas.&#x0D; Conclusiones: el uso del IEO con distintos marcadores ayuda a la especificidad del diagnóstico del EO, pero para que la elección de los marcadores sea la correcta, esta debe estar definida por el objetivo y el diseño del estudio, así como por la relevancia clínica en los sujetos seleccionados, tal cual fue el aplicado en el ensayo realizado. Los resultados obtenidos demuestran la potencialidad del uso de la terapia antioxidante en DMT2, pero no así en la DMT1. La importancia clínica de los biomarcadores del EO en humanos debe provenir de un análisis crítico de los marcadores que refleje el estado general de redox en condiciones particulares y una orientación para una terapia antioxidante efectiva.

Thromboxane A2 receptor contributes to the activation of rat pancreatic stellate cells induced by 8-epi-prostaglandin F2α.

BackgroundPancreatic stellate cells (PSCs) activation plays a critical role in the development of chronic pancreatitis. Previous studies confirmed that thromboxane A2 receptor (TxA2r) was overexpressed in activated PSCs in rats. The purpose of this study was to investigate the role of TxA2r in the activation of PSCs induced by 8-epi-prostaglandin F2α (8-epi-PGF2α).MethodsTxA2r expression in both quiescent and activated PSCs was detected by immunocytochemistry and immunoblot assay. Isolated PSCs were treated with 8-epi-PGF2α (10−6, 10−7, 10−8 mol/L) for 48 h, and SQ29548 (10−4, 10−6, and 10−7 mol/L), a TxA2r-specific antagonist for 48 h, respectively, to identify the drug concentration with the best biological effect and the least cytotoxicity. Then isolated PSCs were treated with SQ29548 (10−4 mol/L) for 2 h, followed by 10−7 mol/L 8-epi-PGF2α for 48 h. Real-time polymerase chain reaction was performed to detect the messenger RNA (mRNA) levels of α-smooth muscle actin (α-SMA) and collagen I. Comparisons between the groups were performed using Student's t test.ResultsTxA2r was up-regulated in activated PSCs in vitro compared with quiescent PSCs (all P < 0.001). Compared with the control group, different concentrations of 8-epi-PGF2α significantly increased mRNA levels of α-SMA (10−6 mol/L: 2.23 ± 0.18 vs. 1.00 ± 0.07, t = 10.70, P < 0.001; 10−7 mol/L: 2.91 ± 0.29 vs. 1.01 ± 0.08, t = 10.83, P < 0.001; 10−8 mol/L, 1.67 ± 0.07 vs. 1.00 ± 0.08, t = 11.40, P < 0.001) and collagen I (10−6 mol/L: 2.68 ± 0.09 vs. 1.00 ± 0.07, t = 24.94, P < 0.001; 10−7 mol/L: 2.12 ± 0.29 vs. 1.01 ± 0.12, t = 6.08, P < 0.001; 10−8 mol/L: 1.46 ± 0.15 vs. 1.00 ± 0.05, t = 4.93, P = 0.008). However, different concentrations of SQ29548 all significantly reduced the expression of collagen I (10−4 mol/L: 0.55 ± 0.07 vs. 1.00 ± 0.07, t = 10.47, P < 0.001; 10−6 mol/L: 0.56 ± 0.10 vs. 1.00 ± 0.07, t = 6.185, P < 0.001; 10−7 mol/L: 0.27 ± 0.04 vs. 1.00 ± 0.07, t = 15.41, P < 0.001) and α-SMA (10−4 mol/L: 0.06 ± 0.01 vs. 1.00 ± 0.11, t = 15.17, P < 0.001; 10−6 mol/L: 0.28 ± 0.03 vs. 1.00 ± 0.11, t = 11.29, P < 0.001; 10−7 mol/L: 0.14 ± 0.04 vs. 1.00 ± 0.11, t = 12.86, P < 0.001). After being treated with SQ29548 (10−4 mol/L) and then 8-epi-PGF2α (10−7 mol/L), the mRNA levels of α-SMA (0.20 ± 0.08 vs. 1.00 ± 0.00, t = 17.46, P < 0.001) and collagen I (0.69 ± 0.13 vs. 1.00 ± 0.00, t = 4.20, P = 0.014) in PSCs were significantly lower than those of the control group.ConclusionsThe results show that 8-epi-PGF2α promoted PSCs activation, while SQ29548 inhibited PSCs activation induced by 8-epi-PGF2α. The result indicated that TxA2r plays an important role during PSC activation and collagen synthesis induced by 8-epi-PGF2αin vitro. This receptor may provide a potential target for more effective antioxidant therapy for pancreatic fibrosis.

S-methyl-L-cysteine Protects against Antimycin A-induced Mitochondrial Dysfunction in Neural Cells via Mimicking Endogenous Methionine-centered Redox Cycle

SummaryMitochondrial superoxide overproduction is believed to be responsible for the neurotoxicity associated with neurodegeneration. Mitochondria-targeted antioxidants, such as MitoQ, have emerged as potentially effective antioxidant therapies. Methionine sulfoxide reductase A (MsrA) is a key mitochondrial-localized endogenous antioxidative enzyme and it can scavenge oxidizing species by catalyzing the methionine (Met)-centered redox cycle (MCRC). In this study, we observed that the natural L-Met acted as a good scavenger for antimycin A-induced mitochondrial superoxide overproduction in PC12 cells. This antioxidation was largely dependent on the Met oxidase activity of MsrA. S-methyl-L-cysteine (SMLC), a natural analogue of Met that is abundantly found in garlic and cabbage, could activate the Met oxidase activity of MsrA to scavenge free radicals. Furthermore, SMLC protected against antimycin A-induced mitochondrial membrane depolarization and alleviated 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity. Thus, our data highlighted the possibility for SMLC supplement in the detoxication of mitochondrial damage by activating the Met oxidase activity of MsrA.

Systemic Redox Imbalance in Patients with Chronic Granulomatous Disease.

The aim of our study was to evaluate redox status, enzymatic and non-enzymatic antioxidant barriers, oxidative damage of proteins, lipids and DNA, as well as concentration of coenzyme Q10 and vitamins A and E in patients with chronic granulomatous disease (CGD). The study was performed on fifteen Caucasian individuals (median age 24 years and seven months) diagnosed with CGD. The mutation in the NCF1 gene was confirmed in ten patients, and in the CYBB gene in five patients. We demonstrated high levels of total oxidant status (TOS) and oxidative stress index (OSI), lipids (↑8-isoprostanes (8-isoP), ↑4-hydroxynonenal (4-HNE)), proteins (↑advanced oxidation protein products (AOPP)) and DNA (↑8-hydroxy-2’-deoxyguanosine (8-OHdG)) oxidation products in CGD individuals as compared to sex- and age-matched healthy controls. We showed enhanced serum enzymatic activity of catalase (CAT) and superoxide dismutase-1 (SOD) and significantly decreased coenzyme Q10 concentration. Our study confirmed redox disturbances and increased oxidative damage in CGD patients, and indicated the need to compare redox imbalance depending on the type of mutation and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The question regarding effectiveness of antioxidant therapy in patients with CGD is open, and the need to establish guidelines in this area remains to be addressed.