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Simple Summary: Oxidative stress, defined as a disturbance in the balance between the production of reactive oxygen species and antioxidant defences, is discussed in relation to its possible role in many pathological conditions, including carcinogenesis. The identification of the oxidative and nitrosative modification of proteins and the definition of their roles in clear cell renal cell carcinoma may be helpful in the elaboration of targeted therapeutic approaches to mitigate protein damage. Therefore, this study aimed to investigate the status of oxidative/nitrosative stress and to explore its role in the development and progression. Oxidative stress increased with the progression of the disease assessed according to the TNM classification and histological grade. Moreover, the presence of angioinvasion in the patients affected the level of nitrite/nitrate, lipid peroxidation and total antioxidant capacity of serum. This is the first report presenting the level of oxidative/nitrosative stress markers among clear cell renal cell carcinoma patients with and without angioinvasion. Oxidative stress is believed to be a factor in the development and progression of renal cell carcinoma (RCC). The identification of the oxidative and nitrosative modification of proteins and the definition of their roles in clear cell RCC (ccRCC) may be helpful in the elaboration of targeted therapeutic approaches to mitigate protein damage. This study aimed to investigate the status of oxidative/nitrosative stress and to explore its role in the development and progression. The studied group consisted of 48 newly diagnosed ccRCC and 30 healthy controls. Serum levels of oxidative stress markers—advanced oxidation protein products (AOPP), thiol groups, Amadori reaction products, 3-nitrotyrosine, nitrate/nitrite, malondialdehyde (MDA), 4-hydroxy-2-nonenal and total antioxidant capacity (TAC)—were determined. Additionally, associations between tumour stage assessed according to TNM classification, histological grade, and the effect of the presence of angioinvasion on the level of stress markers were evaluated. The levels of Amadori products, 3-nitrotyrosine, and nitrate/nitrite were elevated, while the levels of thiol groups and TAC decreased in the ccRCC group. The levels of AOPP, Amadori, and 3-nitrotyrosine increased, and thiol groups and TAC levels decreased with the increasing pathological stage of the tumour. In the case of advanced histological assessment of the tumour, we found decreasing levels of thiol groups and increasing levels of MDA. In patients with angioinvasion, nitrate/nitrite and MDA levels were significantly elevated compared to those in patients without angioinvasion. Oxidative stress increased with the progression of the disease assessed according to the TNM and histological grade. These results demonstrate systemic oxidative stress in ccRCC, suggesting the therapeutic application of antioxidants. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is an autoimmune disease caused by production of antibodies against acetylcholine receptors of the neuromuscular junction (Ab). The aim of this study was to ascertain if oxidative stress accompanies MG by estimation of the several independent parameters of oxidative damage, mainly the levels of oxidative modifications of blood serum proteins. The group studied consisted of 50 MG patients (28 females and 22 males), 24 with ocular MG (OMG) and 26 with generalized MG (GMG), of mean age of 66.7 (30–81) years (y), mean disease duration of 9.5 (0.5–34) y, mean level of Ab of 8.9 (0.1–85) nmol/ml, and 25 age-matched healthy controls. MG patients were stratified into groups according to disease duration (< 5 y or > 5 y), Ab level (low, < 3 or high, > 3 nmol/l) as well as symptoms (GMG or OMG). Glycophore fluorescence was increased in OMG a . Dityrosine was increased in both types of MG c , in patients ill < 5 b and > 5 c y, with low c and high c levels of Ab. N-formylkynurenine was increased in OMG a and GMG b , in both disease duration groups a , in the group of low Ab a . Kynurenine was increased in the group with high Ab a . Tryptophan fluorescence was decreased in OMG b and GMG c , in patients ill for < 5 b and > 5 a y, with low a and high c Ab. Serum thiol group concentration were decreased in GMG c , in patients ill for > 5 y b . AOPP level was elevated in OMG a , in patients ill for > 5 y a with high Ab a . Protein carbonyls were increased in both OMG c and GMG c , in patients ill for > 5 a y, with low b and high b Ab. FRAP and ABTS • scavenging by fast antioxidants were unchanged, but ABTS • scavenging by slow antioxidants was lower in OMG b and GMG c , in patients ill for > 5 c y, in patients with low c and high b Ab ( a p < 0.05, b p < 0.01, c p < 0.001). These results demonstrate systemic oxidative stress in MG, suggesting therapeutic use of antioxidants. [ABSTRACT FROM AUTHOR]

Exercise training is employed as supplementary therapy to patients with heart failure due to its multiple beneficial cardiac effects including physiological remodeling of the heart. However, precautions might be taken for the concomitant high oxidant release. Nigella sativa (NS) has been found to induce cardiac hypertrophy and enhance cardiac function. Combination of NS supplementation and exercise training might induce a safer model of cardiac hypertrophy. Our aim was to study biomarkers associated with cardiac hypertrophy induced by NS supplementation of exercise-trained rats. Forty-five adult male Wistar rats (body weight 150-220 g) were divided equally into three groups: control, exercise-trained (ET) and NS-treated-exercise-trained (NSET) groups. Daily 800 mg/kg NS was administered orally to NSET group for 8 weeks. Rats of the ET and NSET groups were subjected to treadmill running sessions for 2 h/day for 8 weeks. By the end of the experiment, the following were recorded: body, heart and left ventricular weights (BW, HW, LVW), cardiomyocyte diameter, serum growth hormone, insulin growth factor-I (IGF-I), thyroid hormones, catecholamines, total nitrate, ICAM and antioxidant capacity. A homogenous cardiac hypertrophy was evidenced by increased HW/BW, LVW/BW ratios and cardiomyocyte diameter in the two groups of exercise-trained compared with control rats. Rats of ET group had higher growth hormone. Those of NSET group developed higher IGF-I and total antioxidant capacity, as well as lower serum thyroxin level. Simultaneous NS supplementation to an exercise training program preserves and augments exercise-induced physiological cardiac hypertrophy with step-forward adaptive signs of increased IGF-I and reduced thyroxin level, and with an added advantage of elevation of total serum antioxidant capacity. Thus, the novel model of NSET-induced cardiac hypertrophy might be introduced as a new therapeutic strategy for the treatment of heart failure with superior advantages to exercise training alone. [ABSTRACT FROM AUTHOR]

Background and Aims: Oxidative stress (OS) induces the production of fibroblast growth factor 21 (FGF21). Previous data have revealed that FGF21 protects cells from OS injury and death, making it a potential therapeutic option for many diseases with increased OS. However, the association of this growth factor with OS markers in humans with chronic kidney disease (CKD) remains unknown. This study aims to evaluate the association of serum FGF21 with serum total antioxidant capacity (TAC) and oxidized low-density lipoproteins (OxLDL) in subjects in different stages of kidney disease., Methods: This is a cross-sectional study that included 382 subjects with different stages of CKD, irrespective of type 2 diabetes (T2D) diagnosis. Associations of serum FGF21 with OxLDL, TAC, sex, age, body mass index (BMI), fasting plasma glucose, estimated glomerular filtration rate (eGFR), T2D, and smoking, were evaluated through bivariate and partial correlation analyses. Independent associations of these variables with serum FGF21 were evaluated using multiple linear regression analysis., Results: Serum FGF21 was significantly and positively correlated with age ( r  = 0.236), TAC (lnTAC) ( r  = 0.217), and negatively correlated with eGFR ( r  = -0.429) and male sex ( r  = -0.102). After controlling by age, sex, BMI, T2D, smoking, and eGFR; both TAC and OxLDL were positively correlated with FGF21 ( r  = 0.117 and 0.158 respectively, p  < 0.05). Using multiple linear regression analysis, eGFR, male sex, T2D, OxLDL, and TAC were independently associated with serum FGF21 (STDβ = -0.475, 0.162, -0.153, 0.142 and 0.136 respectively; p  < 0.05 for all) adjusted for age, BMI, smoking, and fasting plasma glucose., Conclusion: A positive association between serum FGF21 and OS has been found independently of renal function in humans. Results from the present study provide novel information for deeper understanding of the role of FGF21 in OS in humans with CKD and T2D; mechanistic studies to explain the association of serum FGF21 with oxidative stress in CKD are needed., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Objective To determine whether there was an association between serum total antioxidant capacity (TAC) levels prior to in liver transplantation (LT) for hepatocellular carcinoma (HCC) and 1-year LT mortality. Methods This observational retrospective single-centre study of patients with LT for HCC measured serum levels of TAC and malondialdehyde (as a biomarker of lipid peroxidation) before LT. The study endpoint was 1-year LT mortality. Results This study included 142 patients who underwent LT for HCC. Patients who survived the first year ( n = 127) had significantly lower aged liver donors, significantly higher serum TAC levels, and significantly lower serum malondialdehyde levels compared with the non-survivors ( n = 15). Logistic regression analysis found that serum TAC levels (odds ratio [OR] 0.275; 95% confidence interval [CI] 0.135, 0.562) and the age of the LT donor (OR 1.050; 95% CI 1.009, 1.094) were associated with 1-year LT mortality. There was an inverse association between serum levels of TAC and malondialdehyde levels (rho = -0.22). Conclusions There was an association between low serum TAC levels prior to LT for HCC and mortality during the first year after LT. There was an inverse association between serum TAC levels and lipid peroxidation as measured by malondialdehyde levels.

Preeclampsia (PE) is one of the major disorders in pregnancy leading to many adverse maternal outcomes. Although the etiology of PE is not fully understood, resent studies suggest that an imbalance between free radicals production and the antioxidant defense system might have key role. Our aim of the current study was to evaluate the association between dietary total antioxidant capacity (TAC), serum TAC and risk of PE in women with preeclampsia and normal pregnancy. This case-control study conducted on 55 women with preeclampsia and 93 with normal pregnancy. Dietary intakes were obtained by a semi-quantitative food frequency questionnaire (FFQ) with 168 itmes. Dietary TAC was assessed according to United States Department of Agriculture (USDA) Database for oxygen radical absorbance capacity (ORAC), Release 2. Serum TAC was measured by a double-antibody sandwich enzyme-linked immunesorbent assay (ELISA). After adjusting for energy, pre-pregnant body mass index (BMI) and history of PE, no relationship was found between intake of hydrophilic-ORAC (H-ORAC), lipophilic-ORAC (L-ORAC), total phenolics (TP), total-ORAC (T-ORAC), and PE risk. However, serum TAC had a significant positive relationship with the risk of PE after adjusting for energy (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.16-0.35), BMI and history of PE (OR, 0.04; 95% CI, 0.01-0.32). Findings of this study indicate that serum TAC is positively associated with the risk of PE but no association was found between intake of antioxidant indices and PE risk., Competing Interests: The authors declare that they have no competing interests.