Modern biomarkers of oxidative stress estimated by immuno-enzymal analysis

The literature review presents the results of studies carried out in the world over the past years, devoted to the study of factors and markers of oxidative stress in the development of therapeutic diseases, especially cardiovascular diseases. The article describes the results of studies using enzyme immunoassay of such biomarkers of oxidative stress as glutathione peroxidase, superoxide dismutase, oxidatively modified low density lipoproteins, carbonylated proteins, as well as the general antioxidant capacity of the blood.

Fatty Acid Oxidation and Pro-Resolving Lipid Mediators Are Related to Male Infertility

Specialized pro-resolving lipid mediators regulate the resolution of acute inflammation. They are formed by enzymatic oxygenation of polyunsaturated fatty acids and are divided into families including lipoxins, resolvins, protectins, and maresins. Resolvin D1 (RvD1), produced by docosahexaenoic acid, exerts anti-inflammatory and pro-resolving activities. This research aimed to investigate the implication of seminal RvD1 in human infertility. Infertile patients (n° 67) were grouped based on pathological reproductive conditions as idiopathic infertility, varicocele, and leukocytospermia; the fourth group was composed of fertile men (n° 18). Sperm characteristics were evaluated by light microscopy (WHO guidelines) and by transmission electron microscopy (TEM). The seminal levels of RvD1 and F2-isoprostane (F2-IsoPs) were dosed. In twenty men (6 fertile men, 8 with varicocele, 6 with leukocytospermia) seminal phospholipase A2, iron, cholesterol, transferrin, estradiol, ferritin, testosterone, and sperm membrane fatty acids were detected. The results indicated that: (i) RvD1 amount was positively correlated with F2-IsoPs and reduced sperm quality; (ii) RvD1 levels were significantly higher in patients with leukocytospermia, varicocele, and idiopathic infertility compared to fertile men; (iii) RvD1 increased along with other markers of oxidative stress and inflammation as fatty acids content and clinical biomarkers. This study suggests a panel of inflammatory markers and lipid mediators for a diagnosis of inflammatory status and a subsequent appropriate therapeutic approach.

Biological Anti-TNF-α Therapy and Markers of Oxidative and Carbonyl Stress in Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) as a chronic inflammatory disease is associated with oxidative stress. Drugs targeting tumor necrosis factor-alpha (TNF-α) ameliorate inflammation and symptoms of RA in most patients. Whether markers of oxidative stress can be used for monitoring of treatment effects is unknown. The aim of our study was to analyze the effects of anti-TNF-α treatment on oxidative stress in plasma and saliva of patients with RA. Samples were collected from 26 patients with RA at baseline as well as 3 and 6 months after starting the anti-TNF-α treatment. Thiobarbituric acid-reacting substances (TBARS), advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), and fructosamine were quantified using spectrophotometry and spectrofluorometry in plasma. TBARS were measured also in saliva. The disease activity score (DAS28) was used to assess the clinical status of patients. No significant dynamic changes were found except plasma TBARS that decreased continuously. At 6 months after starting the treatment, plasma TBARS were lower by 39% in comparison to baseline ( p = 0.006 ). Salivary concentrations of TBARS did not reflect the dynamics in plasma. Although a trend was observed ( r = 0.33 ), a significant correlation between plasma TBARS and DAS28 was not found. Our results indicate that anti-TNF-α treatment decreases plasma TBARS as a marker of lipid peroxidation. However, the lack of a significant correlation with DAS28 suggests that it cannot be used for monitoring of treatment. Other markers of oxidative stress and antioxidant capacity with lower biological variability should be tested in future studies.

Higher Angiotensin II type 1 receptor (AT1R) levels and activity in the post-mortem brains of older persons with Alzheimer's disease

Aging is a key risk factor in Alzheimer's dementia (AD) development and progression. The primary dementia-protective benefits of Angiotensin II subtype 1 receptor (AT1R) blockers are believed to arise from systemic effects on blood pressure. However, a brain-specific renin-angiotensin system (b-RAS) exists, which can be altered by AT1R blockers. Brain RAS acts mainly through three angiotensin receptors: AT1R, AT2R, and AT4R. Changes in these brain angiotensin receptors may accelerate the progression of AD. Using post-mortem frontal cortex brain samples of age- and sex-matched cognitively normal individuals (n = 30) and AD patients (n = 30), we sought to dissect the b-RAS changes associated with AD and assess how these changes correlate with brain markers of oxidative stress, inflammation, and mitochondrial dysfunction as well as amyloid-β and paired helical filament tau pathologies. Our results show higher protein levels of the pro-inflammatory AT1R and phospho-ERK (pERK) in the brains of AD participants. Brain AT1R levels and pERK correlated with higher oxidative stress, lower cognitive performance, and higher tangle and amyloid-β scores. This study identifies molecular changes in b-RAS and offers insight into the role of b-RAS in AD-related brain pathology.

Peroxiredoxins as Markers of Oxidative Stress in IgA Nephropathy, Membranous Nephropathy and Lupus Nephritis

IgA nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN) represent important causes of chronic kidney disease. They belong to the immune-mediated glomerulonephritis (GNs), and have distinct pathogenesis, distinct clinical courses, and variable responses to treatment. Therefore, specific diagnostic procedures are necessary for more effective patient management. Recently, a role for oxidative stress has been proposed in various renal disorders. Thus, molecules related to oxidative stress, such as 2-Cys-peroxiredoxins (PRDXs), may represent plausible candidates for biomarkers in renal pathologies. The aim of this study was to assess whether there are differences between individual GNs and healthy controls in the context of PRDXs serum concentration. We enrolled 108 patients with biopsy-proven IgAN (47), MN (26), LN (35) and 30 healthy age- and sex-matched controls. The serum concentrations of PRDX 1–5 were measured with ELISA assays and correlated with demographic and clinical data. The PRDXs’ concentration varied depending on the GN type. We also observed an association of PRDXs with lower estimated glomerular filtration rates, complement, hemoglobin, and body mass index. Our study indicates that individual PRDX can play roles in pathophysiology of selected GNs and that their serum concentrations may become useful as a new supplementary diagnostic markers in IgAN, MN as well as LN. The results of this study open a new avenue for prospective research on PRDXs in renal diseases.

Evaluation of Therapeutic Effects of Quercetin Against Achilles Tendinopathy in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Metalloproteinases

Background: Achilles tendinopathy, seen in athletes and manual labor workers, is an inflammatory condition characterized by chronic tendon pain. Owing to the toxicity that develops in various organs attributed to the use of anti–inflammatory drugs, there is a need for new therapeutic agents. Purpose: In the present study, the effects of quercetin (Que), the one that attracted the most attention of researchers studying this group of flavonoids, were investigated against collagenase–induced tendinopathy. Study Design: Controlled laboratory study. Methods: A total of 35 Sprague-Dawley rats were used in the study. Tendinopathy was created by injecting a single dose of collagenase (10 μL; 10 mg/mL) into the tendons of rats. Thirty minutes after the injection, Que was administered at doses of 25 or 50 mg/kg. Que administration was carried out for 7 days. Animals underwent a motility test at the end of the study. In addition, markers of oxidative stress, inflammation, apoptosis, and autophagy, as well as the expression levels of matrix metalloproteinases (MMPs 2, 3, 9, and 13), ICAM-1, and STAT3, were measured in tendon tissues with biochemical, molecular, and Western blot techniques. Results: The results showed that oxidative stress, inflammation, apoptosis, and autophagy were triggered by the injection of collagenase. In addition, MMPs, ICAM-1, and STAT3 were activated to participate in the development of tendinopathy. Que was found to reduce ICAM-1 levels in tendon tissue. Moreover, Que showed antioxidant, anti–inflammatory, antiapoptotic, and antiautophagic effects on tendons against tendinopathy. More important, Que suppressed the expression of MMPs in the tendon tissues. Conclusion: Que has protective properties against collagenase–induced tendon damage in rats. Clinical Relevance: We believe that with further study, Que may be shown to be an alternative treatment option for athletes or others who experience tendon injuries.

Angiotensin System Modulations in Spontaneously Hypertensive Rats and Consequences on Erythrocyte Properties; Action of MLN-4760 and Zofenopril

Various pathologies (COVID-19 including) are associated with abnormalities in erythrocyte properties. Hypertension represents an unfavorable condition for erythrocyte quality and is the most prevalent risk factor in COVID-19 patients. ACE2 downregulation that is typical of these patients can further deteriorate cardiovascular health; however, its consequences on erythrocyte properties are not known yet. The aim was to investigate the effect of ACE2 inhibition and the potential beneficial effect of zofenopril on erythrocytes in spontaneously hypertensive rats. ACE2 inhibition induced by MLN-4760 (1 mg/kg/day for 2 weeks) led to deterioration of erythrocyte morphology and osmotic resistance, but plasma markers of oxidative stress, erythrocyte deformability, nitric oxide production and Na,K-ATPase activity were not significantly affected. Zofenopril administration (10 mg/kg/day, initiated after 4-day-lasting ACE2 inhibition) resulted in unexpected increase in angiotensin II plasma levels in both control and ACE-inhibited spontaneously hypertensive rats, but in normalization of osmotic resistance in ACE2-inhibited rats. The overall effect of zofenopril on erythrocyte qualities could be evaluated as beneficial.

Influence of Classical Massage on Biochemical Markers of Oxidative Stress in Humans: Pilot Study

Classical massage is one of the most popular forms of conservative treatment in various diseases. Despite the wide scope of research, the mechanisms of massage are not fully known and understood. Apart from the well-described effects on individual body systems, there are few scientific reports on the effects of massage on the human body at the subcellular level. The study was designed to assess changes in oxidative stress parameters in healthy volunteers after a single session of classical massage. 29 healthy volunteers aged 22.24 ± 3.64 participated in the study. Before and 30 minutes after the massage procedures, blood samples were taken by experienced personnel. Biochemical markers of oxidative homeostasis were assessed with highly specific methods for each parameter: oxidase ceruloplasmin, glutathione, malondialdehyde, glutathione peroxidase, glutathione S-transferase, and superoxide dismutase. The study demonstrates that massage therapy caused statistically significant decrease in the concentration of glutathione peroxidase (red blood cells) and increase in the level of glutathione peroxidase (plasma), superoxide dismutase, and malondialdehyde. In contrast, statistically significant changes in the hematocrit, glutathione, NO2-/NO3-, and oxidase ceruloplasmin were not observed. The results show that complex influence of classical massage therapy on human organism may be reflected in parameters of the oxidative stress. To understand this mechanism clearly, further research is needed.

Antioxidative Activity of Wakouba, a Salt Extracted from Elaeis guineensis Jacq in Streptozotocin-Induced Diabetic Rats

Background: Oxidative stress plays a major role in the chronic complications of diabetes, high blood pressure, cancer etc. free radicals such as superoxyde anions, hydrogen peroxides cause severe cell damage. The use of plants is increasingly recommended to treat diseases related to oxidative stress. Aims: This work aims to evaluate the antioxidant properties of Wakouba, a salt extracted from Elaeis guineensis Jacq on biochemical markers of oxidative stress. Place and Duration of Study: Pharmacodynamie-biochemical UPR, Biology and Health Laboratory and Department of Radiology, Services Institute of Medical Sciences (SIMS), Services Hospital Lahore, between March 2017 and July 2018. Materials and Methods: Diabetes was induced in Wistar rats (Rattus norvegicus) by streptozotocin 55 mg / kg bw. The biochemical parameters such as insulin and glycemia, the activities and the level of markers of oxidative stress such as superoxide dismutase (SOD), Catalase (CAT) and Malondialdehyde (MDA) in the aorta, heart and the kidney were determined in the absence and presence of different doses of WAKOUBA (1000 and 2500 mg / kg bw) and GLIBENCLAMIDE, a reference product at 10 and 20 mg / kg bw. Results: The results showed that the administration of streptozotocin at 55 mg / kg bw in rats caused a significant drop (P<0.05) in insulin production followed by a significant increase (P < 0.05) in blood glucose. Similarly, during diabetes, the activities, and levels of oxidative stress markers (SOD, CAT and MDA) increased significantly (P < 0.05). WAKOUBA, at 1000 and 2500 mg / kg bw, significantly normalized insulin production, blood sugar levels, SOD and CAT activities and MDA levels in the aorta, heart, and kidneys in diabetic rats. The same results were obtained with GLIBENCLAMIDE at 10 and 20 mg / kg bw. Conclusion: This study showed that WAKOUBA, a salt extracted from Elaeis guineensis Jacq, lowered and normalized the activities of SOD, CAT and the level of MDA which are markers of oxidative stress in rats made diabetic by streptozocin. WAKOUBA also normalized insulin production and blood sugar levels in diabetic rats. WAKOUBA would have antioxidant properties coupled with antidiabetic properties, which might support its use in traditional medicine to treat diabetes.

Imidacloprid - Induced Pathophysiological Damage in the Midgut of Locusta Migratoria (Orthoptera: Acrididae) in the Field

Neonicotinoids are modern insecticides widely used in agriculture worldwide. Their impact on target (nervous system) and non-target (midgut) tissues has been well studied in beneficial insects including honeybees. However, their effects on pest insects on the field are comparably rarely described. Here, we have studied the effects of the neonicotinoid imidacloprid on the midgut of the pest insect Locusta migratoria caught in the field. We found that in the midgut of imidacloprid-exposed locusts the activity of enzymes involved in reactive oxygen metabolism was perturbed. By contrast, the activity of P450 enzymes that have been shown to be activated in a detoxification response and that were also reported to produce reactive oxygen species was elevated. Probably as a consequence, markers of oxidative stress including protein carbonylation and lipid peroxidation accumulated in midgut samples of these locusts. Histological analyses revealed that their midgut epithelium is disorganized and that the brush border of the epithelial cells is markedly reduced. Indeed, microvilli are significantly shorter, misshapen and possibly non-functional in imidacloprid-treated locusts. We hypothesize that imidacloprid induces oxidative stress in the locust midgut, thereby changing the shape of midgut epithelial cells and probably in turn compromising their physiological function. Presumably, these effects reduce the survival rate of imidacloprid-treated locusts and the damage they cause in the field.