Advanced Oxidation Protein Products Research Articles

Longevity Spinach (Gynura procumbens) Ameliorated Oxidative Stress and Inflammatory Mediators in Cisplatin-Induced Organ Dysfunction in Rats: Comprehensive in vivo and in silico Studies.

This study focused to assess the efficacy of Gynura procumbens (GP) leaf extract against cisplatin (CP)-induced hepatorenal complications in Wister albino rats. Additionally, it aims to detect polyphenolic compounds using high-performance liquid chromatography with diode-array detection (HPLC-DAD). The rats were treated intraperitoneally with CP (7.5 mg/kg) to mediate hepatorenal damage. They were then treated with GP extract (75 and 150 mg/kg, P.O.) for 7 consecutive days. Although GP extract significantly ameliorated CP-mediated hepatorenal biomarkers like alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) levels in a dose-dependent manner, GP extract at 150 mg/kg dose normalized hepatorenal biomarkers ALP (45.11 U/L), ALT (34 U/L), AST (29 U/L), creatinine (10.3 mg/dl) and BUN (11.19 mg/dl) while comparing to control and disease group. Similarly, though it significantly reduced CP-induced oxidative stress inducers, including nitric oxide (NO) and advanced oxidative protein products (AOPP), higher dose (150 mg/kg) exhibited better activity in reducing NO (281.54 mmol/gm tissue in liver and 52.73 mmol/gm tissue in the kidney) and AOPP (770.95 mmol/mg protein in liver and 651.90 mmol/mg protein in the kidney). Besides, it showed better enhancement in the antioxidant enzymes superoxide dismutase, and glutathione levels at a higher dose (150 mg/kg). Histopathological studies showed that CP caused collagen accumulation in the liver and kidney tissues. GP extract drained the collagen mass and acted against hepatorenal damage. Ellagic acid, gallic acid, quercetin hydrate, kaempferol, and rutin hydrate were revealed in GP extract. In-silico modelling showed good docking scores of the polyphenolic compounds with molecular targets including CYP4502E1, NF-κB, caspase-3, and TNF-α. GP could be an effective therapeutic option for management of anticancer drugs' complications like CP-induced organ damage, although clinical studies are required to establish herbal formulation.

Are Advanced Oxidation Protein Products (AOPPs) Levels Altered in Neuropsychiatric Disorders? An Integrative Review.

Neuropsychiatric disorders such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) are considered a public health problem since it interferes in personal relationships and at work. The pathophysiological mechanisms of these mental disorders are still not completely understood. The variety and heterogeneity of symptoms, as well as the absence of biomarkers, make the diagnosis, prognosis, and treatment of these disorders difficult. However, oxidative stress appears to play a role in the pathophysiology of these diseases. In this context, advanced oxidation protein products (AOPPs) are considered a biomarker of protein oxidative damage and have been associated with neuroinflammatory diseases. In patients with neuropsychiatric disorders, increased levels of AOPPs were associated with the severity of symptoms and decreased quality of life. Thus, the objective of this integrative review is to investigate and discuss the relationship between AOPPs levels and MDD, BD, and SZ. Different databases were consulted and approximately 112 scientific articles were found relating AOPPs and psychiatric disorders. In the majority of studies, the blood levels of AOPPs were increased in MDD, BD, and SZ and associated with the severity of the disorders. Although the association of this marker with the risk of developing one of these mental disorders is more uncertain, some studies have suggested this relationship. Of the twenty-four studies highlighted, only four did not find significant differences in AOPPs levels in patients with the disorders mentioned. In summary, it may be suggested that the assessment of AOPPs levels can be a useful tool in the evaluation of neuropsychiatric disorders, at least for prognostic evaluation. However, the role of this biomarker in the pathophysiology of mental disorders is still unclear, as well as whether reducing its levels represents a potential therapeutic strategy.

Reactivation of herpesvirus type 6 and IgA/IgM-mediated responses to activin-A underpin long COVID, including affective symptoms and chronic fatigue syndrome.

Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in long COVID. To investigate whether long COVID and depressive, anxiety, and chronic fatigue syndrome (CFS) symptoms are associated with IgA/IgM/IgG to SARS-CoV-2, human herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers. We examined 90 long COVID patients and ninety healthy controls. We measured serum IgA/IgM/IgG against HHV-6 and EBV and their deoxyuridine 5′-triphosphate nucleotidohydrolase (duTPase), SARS-CoV-2, and activin-A, C-reactive protein (CRP), advanced oxidation protein products (AOPP), and insulin resistance (HOMA2-IR). Long COVID patients showed significant elevations in IgG/IgM-SARS-CoV-2, IgG/IgM-HHV-6, and HHV-6-duTPase, IgA/IgM-activin-A, CRP, AOPP, and HOMA2-IR. Neural network analysis yielded a highly significant predictive accuracy of 80.6% for the long COVID diagnosis (sensitivity: 78.9%, specificity: 81.8%, area under the ROC curve = 0.876); the topmost predictors were as follows: IGA-activin-A, IgG-HHV-6, IgM-HHV-6-duTPase, IgG-SARS-CoV-2, and IgM-HHV-6 (all positively) and a factor extracted from all IgA levels to all viral antigens (inversely). The top 5 predictors of affective symptoms due to long COVID were IgM-HHV-6-duTPase, IgG-HHV-6, CRP, education, IgA-activin-A (predictive accuracy of r = 0.636). The top 5 predictors of CFS due to long COVID were in descending order: CRP, IgG-HHV-6-duTPase, IgM-activin-A, IgM-SARS-CoV-2, and IgA-activin-A (predictive accuracy: r = 0.709). Reactivation of HHV-6, SARS-CoV-2 persistence, and autoimmune reactions to activin-A combined with activated immune-oxidative pathways play a major role in the pathophysiology of long COVID as well as the severity of its affective symptoms and CFS.

Redox Biomarkers - An Effective Tool for Diagnosing COVID-19 Patients and Convalescents.

COVID-19 triggers the overproduction of reactive oxygen species (ROS) which, in combination with a weakened antioxidant barrier, can lead to protein oxidation and lipid peroxidation. The aim of this study was to evaluate enzymatic and non-enzymatic antioxidants, the overall redox potential, and protein and lipid peroxidation products in COVID-19 patients, convalescents, and healthy subjects, and to the determine the diagnostic applicability of these parameters in COVID-19 patients. The study involved 218 patients with COVID-19, 69 convalescents, and 48 healthy subjects who were selected for the research based on age and sex. The study was conducted between 20 February 2021 and 20 November 2021 in Białystok, Poland. The antioxidant barrier, redox status, and oxidative damage products were assessed in serum/plasma samples with the use of colorimetric and spectrophotometric assays. Glutathione reductase (GR) activity was higher, whereas total antioxidant capacity (TAC) was lower in COVID-19 patients than in convalescents (p<0.0001) and the control group (p<0.0001). The concentrations of advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were higher in COVID-19 patients (p<0.0001) and convalescents (p<0.0001) than in the control group. AGEs were the most effective diagnostic biomarker for differentiating COVID-19 patients from the control group (AUC=0.9971) and convalescents from the control group (AUC=1.000). An infection with the SARS-CoV-2 disrupts the redox balance and increases protein oxidation and lipid peroxidation. AGEs fulfill the criteria for a potential diagnostic biomarker in COVID-19 patients and convalescents.

Comparison of the clinical effects of dual-modality endoscopy and traditional laparotomy for the treatment of intra- and extrahepatic bile duct stones.

Bile duct stones (BDSs) may cause patients to develop liver cirrhosis or even liver cancer. Currently, the success rate of surgical treatment for intrahepatic and extrahepatic BDSs is not satisfactory, and there is a risk of postoperative complications. To compare the clinical effects of dual-modality endoscopy (duodenoscopy and laparoscopy) with those of traditional laparotomy in the treatment of intra- and extrahepatic BDSs. Ninety-five patients with intra- and extrahepatic BDSs who sought medical services at Wuhan No.1 Hospital between August 2019 and May 2023 were selected; 45 patients in the control group were treated by traditional laparotomy, and 50 patients in the research group were treated by dual-modality endoscopy. The following factors were collected for analysis: curative effects, safety (incision infection, biliary fistula, lung infection, hemobilia), surgical factors [surgery time, intraoperative blood loss (IBL) volume, gastrointestinal function recovery time, and length of hospital stay], serum inflammatory markers [tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8], and oxidative stress [glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), malondialdehyde (MDA), and advanced protein oxidation products (AOPPs)]. The analysis revealed markedly better efficacy (an obviously higher total effective rate) in the research group than in the control group. In addition, an evidently lower postoperative complication rate, shorter surgical duration, gastrointestinal function recovery time and hospital stay, and lower IBL volume were observed in the research group. Furthermore, the posttreatment serum inflammatory marker (TNF-α, IL-6, and IL-8) levels were significantly lower in the research group than in the control group. Compared with those in the control group, the posttreatment GSH-Px, SOD, MDA and AOPPs in the research group were equivalent to the pretreatment levels; for example, the GSH-Px and SOD levels were significantly higher, while the MDA and AOPP levels were lower. Dual-modality endoscopy therapy (duodenoscopy and laparoscopy) is more effective than traditional laparotomy in the treatment of intra- and extrahepatic BDSs and has a lower risk of postoperative complications; significantly shortened surgical time; shorter gastrointestinal function recovery time; shorter hospital stay; and lower intraoperative bleeding volume, while having a significant inhibitory effect on excessive serum inflammation and causing little postoperative oxidative stress.

NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats.

Aging is closely related to the main aspects of multiple sclerosis (MS). The average age of the MS population is increasing and the number of elderly MS patients is expected to increase. In addition to neurons, N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as immune cells. The aim of this study was to investigate the role of NMDARs in experimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and aged Dark Agouti rats from day 7 after immunization. Antagonizing NMDARs had a more favourable effect on clinical disease, reactivation, and apoptosis of CD4+ T cells in the target organ of aged EAE rats. The expression of the fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent in aged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes' mRNA expression in brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advanced oxidation protein products in brain tissue were consistent with previous results. Overall, our results suggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats.

Advanced Oxidation Protein Products Are Strongly Associated with the Serum Levels and Lipid Contents of Lipoprotein Subclasses in Healthy Volunteers and Patients with Metabolic Syndrome.

The association between advanced oxidation protein products (AOPPs) and lipoprotein subclasses remains unexplored. Therefore, we performed comprehensive lipoprotein profiling of serum using NMR spectroscopy and examined the associations of lipoprotein subclasses with the serum levels of AOPPs in healthy volunteers (HVs) and patients with metabolic syndrome (MS). The serum levels of AOPPs were significantly positively correlated with the serum levels of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL); however, they were significantly negatively correlated with high-density lipoprotein (HDL). These lipoproteins (and their subclasses) differed markedly regarding the direction of correlations between their lipid contents and AOPPs. The strength of the correlations and the relative contributions of the subclasses to the correlations were different in the HVs and patients with MS. As revealed by orthogonal partial least squares discriminant analyses, the serum levels of IDL were strong determinants of AOPPs in the HVs, whereas the serum levels of VLDL and the lipid content of LDL were strong determinants in both groups. We conclude that IDL, VLDL, and LDL facilitate, whereas HDL diminishes the bioavailability of serum AOPPs. The presence of MS and the lipid contents of the subclasses affect the relationship between lipoproteins and AOPPs.

Potential Hepatoprotective Effect of Matricaria Pubescens on High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats.

This study aimed to identify the phytochemical compounds of Matricaria pubescens by LC-MS/MS and evaluate the potential protective effect of its supplementation in high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in adult rats through modulation of oxidative stress and histopathological changes. Twenty-four male rats were randomly divided into four groups. The first group served as control and received the standard diet. The second group (HFD) received a high-fat diet only (30 % of sheep fat). The third group's (control+MP) animals received a standard diet supplemented with 5 % M. pubescens (w/w). The fourth group (HFD+MP) received a high-fat diet supplemented with 5 % M. pubescens for 16 weeks. LC-MS/MS analysis showed that M. pubescens contains many phytochemical compounds. It was observed that the ethanolic extract of M. pubescens has a higher phenolic content than the aqueous extract. The supplementation of M. pubescens (5 % w/w) to HFD rats decreased significantly (p<0.01) body weight, liver and epididymal adipose tissue relative weights, glycemia, triglycerides (TG), insulin resistance, liver markers, TNF-α, malondialdehyde (MDA), protein carbonyl (PCO), advanced oxidation protein products (AOPP) level, and increased reduced glutathione (GSH) level, glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase activities as well as ameliorated histological alterations through the reduction hepatic lipid deposition and adipocytes hypertrophy compared to the HFD group. We conclude that M. pubescens powder may be effective for correcting hyperglycemia, hypertriglyceridemia, insulin resistance, and liver markers while decreasing inflammation and oxidative stress in the liver of high-fat diet-fed rats.

A Preliminary Evaluation of Advanced Oxidation Protein Products (AOPPs) as a Potential Approach to Evaluating Prognosis in Early-Stage Breast Cancer Patients and Its Implication in Tumour Angiogenesis: A 7-Year Single-Centre Study.

Breast cancer (BrC) is a highly prevalent tumour among women. The high incidence and mortality rate of BrC prompts researchers to search for new markers that will provide information on the possible impact of the therapy on the risk of cancer-related events. This study aimed to investigate whether the level of advanced oxidation protein products (AOPPs) may have a potential impact on disease-free (DFS) and overall survival (OS) in BrC patients with early-stage cancer. Additionally, we tried to assess the relationship between AOPPs and angiogenic parameters. In this study, the pre- and post-treatment AOPP levels were examined in the serum of 70 newly diagnosed BrC women. The receiver operating characteristic curve identified pre- and post-treatment AOPPs to be above 9.37 μM and 10.39 μM, respectively, as the best cut-off values to predict the risk of cancer relapse. Additionally, Kaplan-Meier survival analysis indicated that pre- and post-treatment AOPPs above 9.37 μM and 10.39 μM were associated with significantly poorer OS. The uni- and multivariate Cox regression analysis highlighted that lower levels of pre- and post-treatment AOPPs were associated with a longer duration without relapse or cancer-related death. A positive correlation between concentrations of pre-treatment AOPPs and vascular endothelial growth factor A, and negative correlations with levels of soluble forms of vascular endothelial growth factor receptor type 1 and 2, were found. In conclusion, AOPPs appear to have an important role in predicting cancer-related events and may potentially serve as a simple prognostic marker in clinical practice.

Evaluation of the Effects of Alpha-Tocopherol, Quercetin and their Combination on Ethanol-Induced Pancreatic and Duodenal Mucosal injuries: An Experimental Study

Aim: In this study, the effects of alpha-tocopherol (AT), quercetin (QT) or their combination on ethanol-induced pancreatic and duodenal mucosal damage were investigated in rats using morphological and biochemical evaluations.&#x0D; Study Design: Experimental study.&#x0D; Place and Duration of Study: University of Ibadan, Ibadan, Nigeria.&#x0D; Methodology: Ethanol-induced injuries were produced by oral administration of 40% ethanol (0.2 ml/day) for 40 consecutive days, while a control group of rats was served distilled water. Other groups received AT (2.5 mg/kg), QT (50 mg/kg) or their combination with 40% ethanol during the experimental period.&#x0D; Results: Blood glucose level was significantly (p&lt;0.05) increased in ethanol-treated rats relative to controls. Ethanol administration caused shrinkage of insulin-secreting islets tissues in the pancreas, while lesions such as erosions, loss of villi and severe inflammatory cell infiltrations of the mucosa and sub-mucosa were observed in the duodenum. These changes were accompanied by significant elevation in the levels of hydrogen peroxide (H2O2), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) in the pancreas and duodenum, along with reduced activities of glutathione peroxidase (GPx) and glutathione S-transferase (GST). Treatment of rats with AT, QT, and especially their combination, yielded profound reversal of ethanol-induced effects indicated by restoration of blood glucose to control levels, preservation of pancreatic and duodenal morphology and the inhibition of ethanol-induced oxidative stress.&#x0D; Conclusion: Overall, dietary supplementation with AT and/or QT could potentially counteract the adverse effects associated with chronic alcohol consumption.

Increased oxidative stress in shoe industry workers with low-level exposure to a mixture of volatile organic compounds.

This study aimed to assess the redox status and trace metal levels in 49 shoe industry workers (11 men and 38 women) occupationally exposed to a mixture of volatile organic compounds (VOCs), which includes aliphatic hydrocarbons, aromatic hydrocarbons, ketones, esters, ethers, and carboxylic acids. All measured VOCs were below the permitted occupational exposure limits. The control group included 50 unexposed participants (25 men and 25 women). The following plasma parameters were analysed: superoxide anion (O2 •-), advanced oxidation protein products (AOPP), total oxidative status (TOS), prooxidant-antioxidant balance (PAB), oxidative stress index (OSI), superoxide dismutase (SOD) and paraoxonase-1 (PON1) enzyme activity, total SH group content (SHG), and total antioxidant status (TAS). Trace metal levels (copper, zinc, iron, magnesium, and manganese) were analysed in whole blood. All oxidative stress and antioxidative defence parameters were higher in the exposed workers than controls, except for PON1 activity. Higher Fe, Mg, and Zn, and lower Cu were observed in the exposed vs control men, while the exposed women had higher Fe and lower Mg, Zn, and Cu than their controls. Our findings confirm that combined exposure to a mixture of VOCs, even at permitted levels, may result in additive or synergistic adverse health effects and related disorders. This raises concern about current risk assessments, which mainly rely on the effects of individual chemicals, and calls for risk assessment approaches that can explain combined exposure to multiple chemicals.

Exploring the Interplay of Uric Acid and Advanced Oxidation Protein Products Following Myocardial Infarction

Recent studies have underscored the potential elevation of Advanced Oxidation Protein Products (AOPP) and uric acid following myocardial infarction, suggesting their involvement in the development and progression of coronary artery disease and potentially influencing patient outcomes. This study focuses explicitly on examining uric acid and AOPP in the same patients to address the research gap in these biomarkers’ interplay. Recognizing the dual character of uric acid as both an antioxidant and a pro-oxidant, this study delves into its complex biological implications. An analysis was conducted on 40 patients who had experienced myocardial infarction. AOPP levels were quantified using absorbance at 340 nm. Results demonstrated significantly increased AOPP levels in myocardial infarction patients compared to healthy controls, especially in those with high serum uric acid. The serum uric acid and AOPP relationship exhibits a J-shaped curve, indicating a complex, multifactorial interaction. These findings offer new insights into the intricate relationship between serum uric acid and AOPP in myocardial infarction patients, underscoring the significance of these biomarkers in enhancing our understanding of clinical outcomes and informing targeted management strategies for coronary artery disease.

Influence of Maternal Dietary Pattern on the Pro-Oxidant and Antioxidant Status of Mother's Own Milk.

Human milk is essential for a child's best development. However, what a mother eats while breastfeeding can directly influence the composition of mother's milk. This study aimed to assess the antioxidant-oxidant profile of human milk and establish a connection between this profile and the dietary habits of the mothers. A cross-sectional study was conducted at the Hospital Infantil e Maternidade Alzir Bernardino Alves (HIMABA), located in the municipality of Vila Velha-ES, Brazil. The sample included 98 participants. All volunteers completed a structured interview and a Food Frequency Questionnaire. Approximately 5-10 ml of colostrum, transitional milk, and mature milk were manually collected. The antioxidant activity of human milk was assessed using the colorimetric method for free radical scavenging with 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid. Oxidative stress was determined by measuring lipid peroxidation through malondialdehyde concentration, evaluating advanced oxidation protein products, and assessing total protein content using the Bradford method. The antioxidant profile of colostrum was higher than that observed in later phases of milk, whereas pro-oxidants increased in later phases. Maternal dietary patterns influenced the pro-oxidant status of human milk. Participants with a higher daily intake of milk, dairy products, vegetable oils, olive oils, and legumes exhibited lower levels of lipid peroxidation in colostrum, transition milk, and mature milk, respectively. Our study highlights the vital role of a balanced maternal diet in shaping the pro-oxidant status of human milk, with implications for infant health.

Advanced oxidation protein products attenuate the autophagy-lysosome pathway in ovarian granulosa cells by modulating the ROS-dependent mTOR-TFEB pathway

Oxidative stress dysfunction has recently been found to be involved in the pathogenesis of premature ovarian insufficiency (POI). Previously, we found that advanced oxidation protein products (AOPPs) in plasma were elevated in women with POI and had an adverse effect on granulosa cell proliferation. However, the mechanism underlying the effects of AOPPs on autophagy-lysosome pathway regulation in granulosa cells remains unclear. In this study, the effect of AOPPs on autophagy and lysosomal biogenesis and the underlying mechanisms were explored by a series of in vitro experiments in KGN and COV434 cell lines. AOPP-treated rat models were employed to determine the negative effect of AOPPs on the autophagy-lysosome systems in vivo. We found that increased AOPP levels activated the mammalian target of rapamycin (mTOR) pathway, and inhibited the autophagic response and lysosomal biogenesis in KGN and COV434 cells. Furthermore, scavenging of reactive oxygen species (ROS) with N-acetylcysteine and blockade of the mTOR pathway with rapamycin or via starvation alleviated the AOPP-induced inhibitory effects on autophagy and lysosomal biogenesis, suggesting that these effects of AOPPs are ROS-mTOR dependent. The protein expression and nuclear translocation of transcription factor EB (TFEB), the key regulator of lysosomal and autophagic function, were also impaired by the AOPP-activated ROS-mTOR pathway. In addition, TFEB overexpression attenuated the AOPP-induced impairment of autophagic flux and lysosomal biogenesis in KGN and COV434 cells. Chronic AOPP stimulation in vivo also impaired autophagy and lysosomal biogenesis in granulosa cells of rat ovaries. The results highlight that AOPPs lead to impairment of autophagic flux and lysosomal biogenesis via ROS-mTOR-TFEB signaling in granulosa cells and participate in the pathogenesis of POI.

Incremental values of AOPP, IL-6, and GDF15 for identifying arteriosclerosis in patients with obstructive sleep apnea

BackgroundThe objective of this study was to determine the independent and incremental values of advanced oxidative protein product (AOPP), interleukin 6 (IL-6), and growth differentiation factor 15 (GDF15) in identifying arteriosclerosis in patients with obstructive sleep apnea (OSA).MethodsA total of 104 individuals diagnosed with OSA by polysomnography were recruited in our study. Arteriosclerosis was defined by measuring the ultrafast pulse wave velocity of the carotid artery. Peripheral venous blood samples were collected to analyze the levels of AOPP, IL-6, and GDF15 utilizing commercially available enzyme-linked immunosorbent assays.ResultsCompared to OSA patients without arteriosclerosis, those with arteriosclerosis exhibited significantly higher levels of AOPP, IL-6, and GDF15. GDF15 remained significantly associated with arteriosclerosis even after accounting for clinical factors such as age, gender, body mass index, systolic blood pressure, fasting blood glucose, smoking, and the apnea–hypoxia index (AHI). GDF15 demonstrated the largest area under the curve (AUC) for identifying arteriosclerosis in OSA patients (AUC, 0.85 [0.77–0.94]). The logistic regression model, combining clinical factors and AHI, was enhanced by the inclusion of AOPP and IL-6 (Chi-square = 25.06), and even further improved when GDF15 was added (Chi-square = 50.74). The integrated discrimination index increased by 0.06 to 0.16 when GDF15 was added to the models including clinical factors, AOPP, and IL-6.ConclusionsThis study verified the independent and incremental value of GDF15 in identifying arteriosclerosis in OSA patients, surpassing clinical risk factors and other serum biomarkers such as AOPP and IL-6.

Increased levels of advanced oxidation protein products (AOPPs) were associated with nociceptive behavior and clinical scores in an experimental progressive autoimmune encephalomyelitis model (PMS-EAE).

Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system (CNS) generating neuropathic pain and anxiety. Primary progressive MS (PPMS) is the most disabling clinical form, and the patients present an intense neurodegenerative process. In this context, the advanced oxidation protein products (AOPPs) are oxidized compounds and their accumulation in plasma has been related to clinical disability in MS patients. However, the involvement of AOPPs in neuropathic pain- and anxiety-like symptoms was not previously evaluated. To assess this, female mice C57BL/6J were used to induce progressive experimental autoimmune encephalomyelitis (PMS-EAE). Clinical score, weight, strength of plantar pressure, rotarod test, mechanical allodynia, and cold hypersensitivity were evaluated before induction (baseline) and on days 7th, 10th, and 14th post-immunization. We assessed nest building, open field, and elevated plus-maze tests 13 days post-immunization. Animals were killed at 14 days post-immunization; then, AOPPs levels, NADPH oxidase, and myeloperoxidase (MPO) activity were measured in the prefrontal cortex, hippocampus, and spinal cord samples. The clinical score increased 14th post-immunization without changes in weight and mobility. Reduced paw strength, mechanical allodynia, and cold allodynia increased in the PMS-EAE animals. PMS-EAE mice showed spontaneous nociception and anxiety-like behavior. AOPPs concentration, NADPH oxidase, and MPO activity increase in CNS structures. Multivariate analyses indicated that the rise of AOPPs levels, NADPH oxidase, and MPO activity influenced the clinical score and cold allodynia. Thus, we indicated the association between non-stimuli painful perception, anxiety-like, and CNS oxidative damage in the PMS-EAE model.

Protective effect of colchicine on albumin glycation and cellular oxidative stress: Insights into diabetic cardiomyopathy.

The present work elucidates the role of colchicine (COL) on albumin glycation and cellular oxidative stress in diabetic cardiomyopathy (DCM). Human serum albumin (HSA) was glycated with methylglyoxalin the presence of COL (2.5, 3.75, and 5 µM), whereas positive and negative control samples were maintained separately. The effects of COL on HSA glycation, structural and functional modifications in glycated HSA were analyzed using different spectroscopical andfluorescence techniques. Increased fructosamine, carbonyl, and pentosidine formation in glycated HSA samples were inhibited in the presence of COL. Structural conformation of HSA and glycated HSA samples was examined by field emission scanning electron microscopy, circular dichroism, Fourier transform infrared, and proton nuclear magnetic resonance analyses, where COL maintained both secondary and tertiary structures of HSA against glycation. Functional marker assays included ABTS•+ radical scavenging and total antioxidant activities, advanced oxidative protein product formation, and turbidimetry, which showed preserved functional properties of glycated HSA in COL-containing samples. Afterward, rat cardiomyoblast (H9c2 cell line) was treated with glycated HSA-COL complex (400 μg/mL) for examining various cellular antioxidants (nitric oxide, catalase, superoxide dismutase, and glutathione) and detoxification enzymes (aldose reductase, glyoxalase I, andII) levels. All three concentrations of COL exhibited effective anti-glycation properties, enhanced cellular antioxidant levels, and detoxification enzyme activities. The report comprehensively analyzes the potential anti-glycation and properties of COL during its initial assessment.

Pulsed Hyperoxia Acts on Plasmatic Advanced Glycation End Products and Advanced Oxidation Protein Products and Modulates Mitochondrial Biogenesis in Human Peripheral Blood Mononuclear Cells: A Pilot Study on the "Normobaric Oxygen Paradox".

The "normobaric oxygen paradox" (NOP) describes the response to the return to normoxia after a hyperoxic event, sensed by tissues as an oxygen shortage, up-regulating redox-sensitive transcription factors. We have previously characterized the time trend of oxygen-sensitive transcription factors in human PBMCs, in which the return to normoxia after 30% oxygen is sensed as a hypoxic trigger, characterized by hypoxia-induced factor (HIF-1) activation. On the contrary, 100% and 140% oxygen induce a shift toward an oxidative stress response, characterized by NRF2 and NF-kB activation in the first 24 h post exposure. Herein, we investigate whether this paradigm triggers Advanced Glycation End products (AGEs) and Advanced Oxidation Protein Products (AOPPs) as circulating biomarkers of oxidative stress. Secondly, we studied if mitochondrial biogenesis was involved to link the cellular response to oxidative stress in human PBMCs. Our results show that AGEs and AOPPs increase in a different manner according to oxygen dose. Mitochondrial levels of peroxiredoxin (PRX3) supported the cellular response to oxidative stress and increased at 24 h after mild hyperoxia, MH (30% O2), and high hyperoxia, HH (100% O2), while during very high hyperoxia, VHH (140% O2), the activation was significantly high only at 3 h after oxygen exposure. Mitochondrial biogenesis was activated through nuclear translocation of PGC-1α in all the experimental conditions. However, the consequent release of nuclear Mitochondrial Transcription Factor A (TFAM) was observed only after MH exposure. Conversely, HH and VHH are associated with a progressive loss of NOP response in the ability to induce TFAM expression despite a nuclear translocation of PGC-1α also occurring in these conditions. This study confirms that pulsed high oxygen treatment elicits specific cellular responses, according to its partial pressure and time of administration, and further emphasizes the importance of targeting the use of oxygen to activate specific effects on the whole organism.

Tacrolimus trough level and oxidative stress in Tunisian kidney transplanted patients

Background The effect of tacrolimus (TAC) on oxidative stress after kidney transplantation (KT) is unclear. This study aimed to evaluate the influence of TAC trough levels of oxidative stress status in Tunisian KT patients during the post-transplantation period (PTP). Methods A prospective study including 90 KT patients was performed. TAC whole-blood concentrations were measured by the microparticle enzyme immunoassay method and adjusted according to the target range. Plasma levels of oxidants (malondialdehyde (MDA) and advanced oxidation protein products (AOPP)) and antioxidants (ascorbic acid, glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) were measured using spectrophotometry. The subjects were subdivided according to PTP into three groups: patients with early, intermediate, and late PT. According to the TAC level, they were subdivided into LL-TAC, NL-TAC, and HL-TAC groups. Results A decrease in MDA levels, SOD activity, and an increase in GSH levels and GPx activity were observed in patients with late PT compared to those with early and intermediate PT (p < 0.05). Patients with LL-TAC had lower MDA levels and higher GSH levels and GPx activity compared with the NL-TAC and HL-TAC groups (p < 0.05). Conclusion Our results have shown that in KT patients, despite the recovery of kidney function, the TAC reduced but did not normalize oxidative stress levels in long-term therapy, and the TAC effect significantly depends on the concentration used.

Anti-Inflammatory and Immunomodulatory Properties of a Crude Polysaccharide Derived from Green Seaweed Halimeda tuna: Computational and Experimental Evidences.

In this study, we investigated for the first time the anti-inflammatory and immunomodulatory properties of crude polysaccharide (PSHT) extracted from green marine algae Halimeda tuna. PSHT exhibited anti-oxidant activity in vitro through scavenging 1, 1-diphenyl-2-picryl hydroxyl free radical, reducing Fe3+/ferricyanide complex, and inhibiting nitric oxide. PSHT maintained the erythrocyte membrane integrity and prevented hemolysis. Our results also showed that PSHT exerted a significant anti-edematic effect in vivo by decreasing advanced oxidation protein products and malondialdehyde levels and increasing the superoxide dismutase and glutathione peroxidase activities in rat's paw model and erythrocytes. Interestingly, PSHT increased the viability of murine RAW264.7 macrophages and exerted an anti-inflammatory effect on lipopolysaccharide-stimulated cells by decreasing pro-inflammatory molecule levels, including nitric oxide, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-α). Our findings indicate that PSHT could be used as a potential immunomodulatory, anti-inflammatory, anti-hemolytic, and anti-oxidant agent. These results could be explained by the computational findings showing that polysaccharide building blocks bound both cyclooxygenase-2 (COX-2) and TNF-α with acceptable affinities.