Advanced Oxidation Protein Products Concentrations Research Articles

Shedding light on the shadows: oxidative stress and its pivotal role in prostate cancer progression.

Data on oxidative protein damage, total antioxidant capacity (TAC) and lipid peroxidation in progression of prostate cancer remain elusive. So far, the influence of the presence of perineural invasion on the level of oxidative stress has not been described. Additionally, there is limited data on the level of oxidative stress in patients' urine. We compared the levels of oxidative stress markers in serum and urine in 50 patients with prostate cancer depending on the tumor stage and histological grade, the Gleason score, and the presence of perineural invasion. We found a significantly de-creased level of serum thiol groups and TAC in participants with prostate cancer. Similarly, serum Amadori products and malondialdehyde (MDA) were higher in patients than in healthy men. There was a significantly decrease in TAC and a significantly increased MDA in the urine of prostate cancer patients. As the stage of cancer increased, a decrease in the thiol group concentration and TAC as well as an increase in the concentration of lipid peroxidation products in the serum was observed. The serum level of advanced oxidation protein products (AOPP) increased in the group with Gleason scores greater than 7. Furthermore, serum thiol groups and TAC were reduced in the group with Gleason >7 as compared to Gleason <7. The presence of perineural invasion significantly reduced serum and urinary TAC and increased urinary AOPP concentration. These results indicate a significant role for oxidative damage in prostate carcinogenesis and its progression. Characterizing oxidative and nitrosative damage to proteins may be useful in designing targeted therapies for prostate cancer patients.

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.

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.

Assessment of the glutathione system and the biomolecules oxidation products contribution to the state of free radical homeostasis in women of two ethnic groups with insomnia

Own and literature data showed a change in the free radical oxidation products and indicators of the glutathione system concentration in menopausal women with insomnia. The change in the studied parameters depended on the ethnicity of the patients. The aim of the study was to assess the informative value of these indicators and their contribution to the state of free radical homeostasis in menopausal women of Russian and Buryat ethnic groups with insomnia. Material and methods. The study involved women of the menopausal period of the Russian (n = 136) and Buryat ethnos (n = 94). The women underwent a general clinical examination and a questionnaire. Then they were divided into climacteric phases, control groups and groups with insomnia. Enzyme immunoassay, spectrophotometric and fluorometric methods of analysis were used to determine values of glutathione system and biomolecule oxidation products. The informative value of the studied indicators and their contribution to the state of free-radical homeostasis was assessed with the help of discriminant analysis. Results and discussion. The most informative indicators in the group of Russian women with insomnia in perimenopause were content of advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), products of DNA oxidative modification, oxidized glutathione, glutathione reductase activity; in postmenopause – concentration of AOPP, products of DNA oxidative modification, and glutathione reductase activity. In Buryat perimenopausal women the most informative values were content of AGEs, of reduced and oxidized glutathione and their ratio, and in postmenopause – content of AGEs, of oxidized glutathione and glutathione reductase activity. Mathematical models have been developed that demonstrate the prevalence of the redox balance prooxidant component contribution in Russian ethnic group and the antioxidant component in Buryat ethnic group and allow characterizing patients with insomnia with high accuracy depending on the phase of menopause and ethnicity. Conclusions. In women of the Russian ethnic group with insomnia in the menopausal period, the greatest contribution to the state of free radical homeostasis is made by the products of oxidation of biomolecules, which characterizes the predominance of the processes of disadaptation. In women of the Buryat ethnic group, in response to insomnia in the climacteric period, the components of the glutathione system make the greatest contribution to the state of free radical homeostasis, which characterizes the activation of adaptive capabilities throughout the climacteric period.

Melatonin in Newborn Infants Undergoing Surgery: A Pilot Study on Its Effects on Postoperative Oxidative Stress

Surgery is frequently associated with excessive oxidative stress. Melatonin acts as an antioxidant and transient melatonin deficiency has been described in neonatal surgical patients. This randomized, blinded, prospective pilot study tested the hypothesis that oral melatonin supplementation in newborn infants undergoing surgery is effective in reducing perioperative oxidative stress. A total of twenty-three newborn infants requiring surgery were enrolled: 10 received a single dose of oral melatonin 0.5 mg/kg in the morning, before surgery (MEL group), and 13 newborns served as the control group (untreated group). Plasma concentrations of melatonin, Non-Protein-Bound Iron (NPBI), Advanced Oxidation Protein Products (AOPP), and F2-Isoprostanes (F2-IsoPs) were measured. Both in the pre- and postoperative period, melatonin concentrations were significantly higher in the MEL group than in the untreated group (preoperative: 1265.50 ± 717.03 vs. 23.23 ± 17.71 pg/mL, p < 0.0001; postoperative: 1465.20 ± 538.38 vs. 56.47 ± 37.18 pg/mL, p < 0.0001). Melatonin significantly increased from the pre- to postoperative period in the untreated group (23.23 ± 17.71 vs. 56.47 ± 37.18 pg/mL; pg/mL p = 0.006). In the MEL group, the mean blood concentrations of NPBI, F2-IsoPs, and AOPP significantly decreased from the pre- to the postoperative period (4.69 ± 3.85 vs. 1.65 ± 1.18 micromol/dL, p = 0.049; 128.40 ± 92.30 vs. 50.25 ± 47.47 pg/mL, p = 0.037 and 65.18 ± 15.50 vs. 43.98 ± 17.92 micromol/dL, p = 0.022, respectively). Melatonin concentration increases physiologically from the pre- to the postoperative period, suggesting a defensive physiologic response to counteract oxidative stress. The administration of exogenous melatonin in newborn infants undergoing surgery reduces lipid and protein peroxidation in the postoperative period, showing a potential role in protecting babies from the deleterious consequences of oxidative stress.

PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products

Osteoblast apoptosis plays an important role in age-related bone loss and osteoporosis. Our previous study revealed that advanced oxidation protein products (AOPPs) could induce nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species (ROS) production, cause mitochondrial membrane potential (ΔΨm) depolarization, trigger the mitochondria-dependent intrinsic apoptosis pathway, and lead to osteoblast apoptosis and ultimately osteopenia and bone microstructural destruction. In this study, we found that AOPPs also induced mitochondrial ROS (mtROS) generation in osteoblastic MC3T3-E1 cells, which was closely related to NOX-derived ROS, and aggravated the oxidative stress condition, thereby further promoting apoptosis. Removing excessive ROS and damaged mitochondria is the key factor in reversing AOPP-induced apoptosis. Here, by in vitro studies, we showed that rapamycin further activated PINK1/Parkin-mediated mitophagy in AOPP-stimulated MC3T3-E1 cells and significantly alleviated AOPP-induced cell apoptosis by eliminating ROS and damaged mitochondria. Our in vivo studies revealed that PINK1/Parkin-mediated mitophagy could decrease the plasma AOPP concentration and inhibit AOPP-induced osteoblast apoptosis, thus ameliorating AOPP accumulation-related bone loss, bone microstructural destruction and bone mineral density (BMD) loss. Together, our study indicated that therapeutic strategies aimed at upregulating osteoblast mitophagy and preserving mitochondrial function might have potential for treating age-related osteoporosis.

Evaluation of Selected Oxidant/Antioxidant Parameters in Patients with Relapsing-Remitting Multiple Sclerosis Undergoing Disease-Modifying Therapies.

The aim of this study was to evaluate oxidative stress parameters, specifically the concentration of advanced oxidation protein products (AOPP) and ferric-reducing antioxidant power (FRAP), in the serum of patients with relapsing-remitting multiple sclerosis (RRMS). We also analyzed the relationships between each parameter and selected clinical/laboratory multiple-sclerosis-related parameters. The study group comprised 204 patients with RRMS and 29 healthy, age-matched controls. The concentration of AOPP was significantly higher in the RRMS patients than in controls. ROC analysis showed the ability of AOPP to distinguish between the patients with RRMS and controls (the value of AUC was 94.8%, with a sensitivity of 89.69% and specificity of 89.3%). AOPP and FRAP were significantly higher in male than in female RRMS patients. Correlations were found between AOPP and the laboratory markers of inflammation. AOPP differed in the subgroups of patients treated with particular medications. Our findings indicate an increase in the markers of oxidative stress in the serum of RRMS patients, possibly linked with chronic inflammation. Gender and type of treatment affected the markers of oxidative stress.

Are There Associations between Seminal Plasma Advanced Oxidation Protein Products and Selected Redox-Associated Biochemical Parameters in Infertile Male Patients? A Preliminary Report.

Oxidative stress (OS) is one of the reasons for male infertility. Seminal plasma contains a multitude of enzymes and ions which influence OS and thus may affect male fertility. The aim of the study was to check for associations between seminal plasma advanced oxidation protein products (AOPP) concentrations and levels of selected biochemical parameters (total protein, iron, uric acid, magnesium, calcium) in infertile men, and establish whether they are associated with sperm disorders. Seminal plasma AOPP, as well as total protein, iron, uric acid, calcium, and magnesium concentrations, were determined for the following patient groups: normozoospermic (N; n = 33), teratozoospermic (T; n = 30), asthenoteratozoospermic (AT; n = 18), and oligoasthenoteratozoospermic (OAT; n = 28). AOPP concentrations were significantly higher in N and T groups in comparison to AT and OAT groups. Total protein concentrations were significantly lower in the T group in comparison to the AT and OAT groups, whereas iron concentrations significantly decreased in the OAT group in comparison to the T and N patients. AOPP differentiates AT patients from men with other sperm disorders. Our results suggest that asthenozoospermia may be connected with total protein levels. Insufficient iron levels may reflect a decrease in sperm count.

Effect of Advanced Oxidation Protein Products (AOPPs) and aging on the osteoclast differentiation of Myeloid-Derived Suppressor Cells (MDSCs) and its preliminary mechanism

To verify the osteoclast differentiation ability of MDSCs from mice of different ages and explore the effect of AOPPs on the osteoclast differentiation of bone marrow MDSCs.Bone marrow cells from C57BL/6 (a.k.a C57) mice of different ages were subjected to flow cytometry, and CD11b+Ly6C+Ly6G+ MDSCs were sorted out. After induction of osteoclast differentiation, these cells were subjected to tartrate-resistant acid phosphatase (TRAP) and F-actin. MDSCs from bone marrows of old mice were injected into the tibial medullary cavity of young mice. One week later, the bone marrows were subjected to histological examination, TRAP, and cell count. MDSCs from bone marrows of old mice were sorted for induction of osteoclast differentiation, intervened with reactive oxygen species (ROS) scavenger, inducible nitric oxide synthase (iNOS) inhibitor, and nitric oxide (NO) scavenger, and then subjected to TRAP. 8-weeks-old C57 mice were injected with the same concentrations of either AOPPs or mouse serum albumin (MSA). Four weeks later, MDSCs from bone marrows were sorted and subjected to induction of osteoclast differentiation, followed by IHC staining and TRAP. MDSCs of 8-weeks-old C57 mice were extracted and subjected to in vitro induction of osteoclast differentiation with different concentrations of AOPPs, followed by TRAP training.The number of MDSCs in the bone marrows of old mice was significantly higher than that in young mice. MDSCs from bone marrows of old mice differentiated into large multinucleated TRAP+ osteoclasts, which were significantly different from those in the middle-aged and young mice in terms of cell quantity and morphology. The actin rings formed in the differentiated osteoclasts from MDSCs of bone marrows were densely distributed in the whole field of view, which were significantly denser than those in the middle-aged and young mice. After injection of MDSCs of old mice, the number of TRAP + osteoclasts in the tibial medullary cavity of young mice was significantly increased. NO inhibitor can significantly inhibit the osteoclast differentiation capacity of MDSCs from bone marrows of old mice. In vivo treatment with AOPPs significantly increased the proportion of MDSCs in the bone marrow, which is up to 55.2%. After injection of AOPPs in 8-week-old mice and induction of osteoclast differentiation from the MDSCs, the ratios of CD11b+ and Gr1+ cells were significantly higher than that in the control and MSA groups but was not significantly different from that in the 15-month-old mice. Upon in vitro treatment with different concentrations of AOPPs, the MDSCs did not show any sign of osteoclast differentiation.MDSCs can directly undergo osteoclast differentiation, the capacity of which is stronger in MDSCs of bone marrows of old mice; the NO pathway is a potential mechanism underlying this phenomenon. In vivo but not in vitro AOPPs treatment can induce osteoclast differentiation of MDSCs, indicating there might be other factors in the body that can interact with AOPPs to induce osteoclast differentiation of MDSCs.

Iontophoresis Corneal Cross-linking With Oxygen Supplementation in Ovine Eyes.

To evaluate the biomechanical changes and advanced oxidation protein products (AOPP) production after different corneal cross-linking (CXL) protocols with or without oxygen supplementation. Ovine eyes in the study were equally distributed to five groups as control, standard Dresden protocol, diluted alcohol- and iontophoresis-assisted CXL (DAI-CXL), and 0.1% and 0.2% riboflavin-mediated iontophoresis-assisted CXL with oxygen supplementation (I-CXL). Corneas that received CXL were divided into two equal parts, one part was used for uniaxial tensiometry and one part was used for AOPP measurement. All treatment groups showed higher Young's modulus and stiffness compared to the control group (P < .05). Both oxygen-assisted I-CXL groups with 0.1% and 0.2% riboflavin concentrations had higher corneal Young's modulus (P = .009 and .006, respectively) and stiffness (P = .009) values, whereas the DAI-CXL group had lesser Young's modulus and stiffness values (P = .032) compared to the Dresden protocol group. All treatment groups showed higher AOPP concentrations compared to the control group (P < .05). DAI-CXL and I-CXL groups showed similar AOPP formation compared to the Dresden protocol (P = .673). When the epithelium is intact, the desired increase in corneal stiffness might not be achieved. However, increasing the oxygen in the environment might provide a sufficient increase in stiffness in cases undergoing epitheliumon I-CXL, which might be promising in terms of shortening the CXL therapy and decreasing the complications. [J Refract Surg. 2022;38(10):674-681.].

Relationships between Biomarkers of Oxidative Stress in Seminal Plasma and Sperm Motility in Bulls before and after Cryopreservation.

Simple SummaryThe early detection of (in)fertility biomarkers is of great interest in the enhancement of artificial insemination programs, with the objective of providing equal access to food resources and potentially improving conservation strategies for endangered species. (In)Fertility is a complex trait governed by a multitude of physiological, molecular, and external factors, and it has low heritability. Accurately assessing fertility markers in vitro and predicting reproduction outcomes in vivo is thus a difficult task. The current study aimed at evaluating the relationship between sperm motility parameters and oxidative stress (OS) markers of seminal plasma (SP) in bulls before and after cryopreservation. In this study, advanced oxidative protein products (AOPP) and thiol concentrations were found to be positively related to the higher motility of fresh ejaculates; on the other hand, they did not affect the motility parameters of frozen–thawed semen. These observations give an alternative perspective on the relationship between sperm motility and SP composition, in which increased OS in SP does not necessarily negatively affect sperm motility. There are still gaps in the knowledge about the effect of cryopreservation on sperm quality and the role of SP in the process. Nevertheless, sperm motility and OS parameters (AOPP and thiols) could be considered as effective biomarkers of bull (in)fertility.This study aimed at evaluating the relationship between biomarkers of oxidative stress (OS) in seminal plasma and sperm motility in bulls before and after cryopreservation. Three ejaculates per bull were collected from 20 young bulls. Each ejaculate was analyzed for motility before and after cryopreservation (by CASA), and the SP concentration of Advanced Oxidation Protein Products (AOPP), thiols, and carbonyl groups (CT) were examined. Then, based on their motility, the ejaculates were grouped into: high motility fresh (HMF), low motility fresh (LMF), high motility thawed (HMT), and low motility thawed (LMT) groups. Higher AOPP and thiol concentrations on SP were related (p < 0.05) to the higher LIN and BCF and lower ALH of fresh semen. In addition, AOPP and thiols were significantly higher in HMF than LMF. As a confirmation of this, the Receiver Operating Characteristic (ROC) curve analysis showed that AOPP and thiol concentrations in SP were able to discriminate between HMF and LMF ejaculates (Area Under the Curve of 71.67% and 72.04%, respectively). These observations give an alternative perspective on the relationship between sperm motility and the OS parameters of SP, which need further investigations.

The influence of cord blood renalase and advanced oxidation protein products (AOPPs) on perinatal and anthropometric parameters of newborns of mothers with gestational hypertension.

Renalase is an enzyme secreted by the kidneys, which takes part in the regulation of arterial pressure, myocardial contractility and modulation of vascular resistance, but its effect on renalase levels in newborns has not been studied yet. The levels of advanced oxidation protein products (AOPPs) were also evaluated as a marker of oxidative stress. This study examined whether renalase and AOPP levels are different in the cord blood of newborns exposed to gestational hypertension (HT). The association of both factors with perinatal and anthropometric data among the studied patients was assessed. The study included 89 newborns: 30 newborns from the study group, whose mothers were diagnosed with gestational HT, and 59 newborns born from normal pregnancies, who formed the control group. Anthropometric measurements and perinatal data in newborns in both groups were recorded. A significantly lower (p < 0.001) concentration of renalase was found in the study group (median (Q1-Q3): 23.96 μg/mL (20.63-26.91 μg/mL)) as compared to the control group (median (Q1-Q3): 37.54 μg/mL (33.78-40.02 μg/mL)). In case of AOPPs, a significantly higher (p < 0.001) concentration of AOPPs was observed in the study group (median (Q1-Q3): 131.65 μmol/L (113.80-146.10 μmol/L)) than in the controls (median (Q1-Q3): 93.70 μmol/L (87.10-111.20 μmol/L)). A significant difference between renalase and AOPP concentrations between the study and control groups has been demonstrated. Both factors may influence anthropometric and perinatal outcomes of newborns.

Evaluation of Genetic Polymorphisms of the Antioxidant Enzymes and Biomarkers of Oxidative Stress in Preterm Neonates With Respiratory Distress Syndrome Receiving External Surfactant.

Preterm neonates, particularly extremely preterm, are susceptible to respiratory distress syndrome (RDS) due to surfactant deficiency. Single nucleotide polymorphisms (SNPs) in the antioxidant enzymes influence the balance between antioxidant and oxidative stress molecules. To ascertain the role of SNPs of antioxidant enzymes and oxidative stress biomarkers in preterm neonates with RDS. Observational, cross-sectional study. Preterm neonates diagnosed with RDS receiving external surfactant within 24 hours were considered as the cases and those without RDS were the control group. Umbilical cord blood and peripheral blood samples before administering surfactant (day 1), and on days 2 and 3 were collected. Plasma malondialdehyde, 8-hydroxy-2-deoxy guanosine (8-OH-dG), advanced oxidation protein products (AOPP), total antioxidant capacity (TAC), visfatin, reduced glutathione, and chaperonin 60 were evaluated using enzyme-linked immunosorbent assay. SNPs in manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase (Cu/Zn SOD), glutathione peroxidase (GPX1 and GPX3), catalase (CAT), glutathione S-transferase (GSTP1) were evaluated using real-time polymerase-chain-reaction. The receiver-operating characteristics curve was used for predicting the accuracy of biomarkers using the area under the curve (AUC) and 95% confidence intervals (95% CI). GSTP1, MnSOD, and eNOS (rs1799983) SNPs were observed to significantly influence the oxidative biomarker concentrations in the entire study population. SNPs in GSTP1, MnSOD, and eNOS (rs1799983) were significantly associated with differences in oxidative stress biomarkers. MnSOD (rs4880) significantly increased the risk of pulmonary complications in neonates with RDS. DNA damage product (8-OH-dG) concentrations before surfactant administration has the best predictive accuracy (AUC: 0.8; 95% CI: 0.7-1; P = .001) for pulmonary complications with a cut-off value of 5008.8 pg/mL. TAC concentrations are significantly greater on day 2 and day 3 amongst neonates receiving surfactant compared to the control group. AOPP in the umbilical cord blood was observed to significantly predict the severity of RDS (AUC: 0.8; 95% CI: 0.6-1; P = .01) with an optimal cut-off value of 88.78 µmol/L. We observed that SNPs in eNOS and MnSOD significantly influence the production of oxidative stress biomarkers in preterm neonates. Baseline 8-OH-dG concentrations best predict the risk of pulmonary complications and AOPP concentrations in the umbilical cord blood predict the risk of RDS severity.

Improvement in Redox Homeostasis after Cytoreductive Surgery in Colorectal Adenocarcinoma.

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

Advanced Oxidation Protein Products Induce G1/G0-Phase Arrest in Ovarian Granulosa Cells via the ROS-JNK/p38 MAPK-p21 Pathway in Premature Ovarian Insufficiency.

The mechanism underlying the role of oxidative stress and advanced oxidation protein products (AOPPs) in the aetiology of premature ovarian insufficiency (POI) is poorly understood. Here, we investigated the plasma AOPP level in POI patients and the effects of AOPPs on granulosa cells both in vitro and in vivo. KGN cells were treated with different AOPP doses, and cell cycle distribution, intracellular reactive oxygen species (ROS), and protein expression levels were measured. Sprague–Dawley (SD) rats were treated daily with PBS, rat serum albumin, AOPP, or AOPP+ N-acetylcysteine (NAC) for 12 weeks to explore the effect of AOPPs on ovarian function. Plasma AOPP concentrations were significantly higher in both POI and biochemical POI patients than in controls and negatively correlated with anti-Müllerian hormone and the antral follicle count. KGN cells treated with AOPP exhibited G1/G0-phase arrest. AOPP induced G1/G0-phase arrest in KGN cells by activating the ROS-c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK)-p21 pathway. Pretreatment with NAC, SP600125, SB203580, and si-p21 blocked AOPP-induced G1/G0-phase arrest. In SD rats, AOPP treatment increased the proportion of atretic follicles, and NAC attenuated the adverse effects of AOPPs in the ovary. In conclusion, we provide mechanistic evidence that AOPPs may induce cell cycle arrest in granulosa cells via the ROS-JNK/p38 MAPK-p21 pathway and thus may be a novel biomarker of POI.

Serum Biomarkers in Differential Diagnosis of Idiopathic Pulmonary Fibrosis and Connective Tissue Disease-Associated Interstitial Lung Disease.

Introduction: The goal of this study is to determine whether Advanced glycosylated end-products (AGE), Advanced oxidation protein products (AOPP) and Matrix metalloproteinase 7 (MMP7) could be used as differential biomarkers for idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). Method: Seventy-three patients were enrolled: 29 with IPF, 14 with CTD-ILD, and 30 healthy controls. The study included a single visit by participants. A blood sample was drawn and serum was analysed for AGE using spectrofluorimetry, AOPP by spectrophotometry, and MMP7 using sandwich-type enzyme-linked immunosorbent assay. Results: AGE, AOPP and MMP7 serum levels were significantly higher in both IPF and CTD-ILD patients versus healthy controls; and AGE was also significantly elevated in CTD-ILD compared to the IPF group. AGE plasma levels clearly distinguished CTD-ILD patients from healthy participants (AUC = 0.95; 95% IC 0.86–1), whereas in IPF patients, the distinction was moderate (AUC = 0.78; 95% IC 0.60–0.97). Conclusion: In summary, our results provide support for the potential value of serum AGE, AOPP and MMP7 concentrations as diagnostic biomarkers in IPF and CTD-ILD to differentiate between ILD patients and healthy controls. Furthermore, this study provides evidence, for the first time, for the possible use of AGE as a differential diagnostic biomarker to distinguish between IPF and CTD-ILD. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF and CTD-ILD diagnosis needs to be considered and further explored. Multicentre studies are necessary to understand the role of AGE in differential diagnosis.

Advanced oxidation protein products trigger apoptosis and block epithelial-to-mesenchymal transition in crypt epithelial cells.

Advanced oxidation protein products (AOPPs) are uremic toxins. The present study aimed to investigate the effects of AOPPs on the epithelial mesenchymal transition (EMT) and apoptosis of rat crypt epithelial cells, and to assess the signaling pathways involved. The oxidized rat serum albumin was obtained by sodium hypochlorite modification as AOPPs, and the rat serum albumin (RSA) without sodium hypochlorite modification was set as the control. Different concentrations of AOPPs or RSA were incubated with rat crypt epithelial cells (IEC-6 cells). After culturing for 48 and 72 h, apoptosis was detected by flow cytometry. IEC-6 cells were divided into three groups: A normal group, an AOPPs group and an RSA group. Three groups of cells were collected following treatment for 2 h, and the phosphorylation levels of Akt and p65 NF-κB were detected by western blotting. After 72 h of treatment, the cells were collected and the apoptotic rate was detected by flow cytometry. The expression of EMT-related proteins was detected by reverse transcription-quantitative polymerase chain reaction and western blotting. The apoptotic rate of IEC-6 cells increased with the concentration of AOPPs, and the apoptotic rate of the AOPPs group was higher than that of the RSA group. The expression of fibronectin, snail, slug and collagen I in the AOPPs group was lower than that in the RSA group, while the expression of E-cadherin was not significantly different between the two groups. In addition, the expression of fibronectin, snail, slug and collagen I genes in the AOPPs-treated group was equal to or lower than that in the normal group. Compared with the normal group, the Akt phosphorylation level was decreased and the p65 phosphorylation level was increased in the AOPPs- or RSA-treated groups. Compared with the AOPPs-treated group, Akt and p65 phosphorylation levels in RSA-treated group were slightly higher. In conclusion, AOPPs trigger apoptosis and inhibit the EMT of rat crypt epithelial cells, which may be associated with the inhibition of Akt phosphorylation and the promotion of p65 phosphorylation.

Serum oxidized low density lipoprotein serves as a mediator for the inverse relationship between serum d-ribose and cognitive performance in type 2 diabetic patients

Chronic hyperglycemia, proinflammatory state, and oxidative stress are implicated in the etiology of mild cognitive impairment (MCI) in type 2 diabetes mellitus (T2DM) patients. However, roles and mechanisms of the diabetes-related dys-regulation of serum d-ribose in the pathogenesis remain unclear. This study was to assess: 1) changes of serum d-ribose in T2DM patients with or without MCI compared with healthy controls; and 2) associations of serum d-ribose with key biomarkers of ribosylation [advanced glycation end products (AGEs) and receptor for advanced glycation end products (RAGE)], inflammation (IL-6 and NF-κB) and oxidative stress [oxidized low density lipoproteins (ox-LDL), advanced oxidation protein products (AOPP), total thiol, and non-protein thiol)]. A cross-sectional study was conducted with 1564 initial participants including 362 T2DM patients. Based on their fasting blood glucose concentrations and Montreal cognitive assessment (MoCA) scores, we selected 89 participants and divided them into three groups: 27 healthy controls, 26 T2DM patients with normal cognition, 36 T2DM patients with MCI. All participants were gone through standard anthropometric tests and biochemical examinations of serum clinical profiles and concentrations of d-ribose, AGE, RAGE, IL-6, NF-κB, ox-LDL, AOPP, total thiol, and non-protein thiol. Serum concentrations of d-ribose, ox-LDL, and AOPP were greater (P < 0.05) in the T2DM-MCI patients than that in the T2DM or controls. Serum d-ribose exhibited a positive correlation (P < 0.05) with serum AGEs, RAGE, ox-LDL, and fasting blood glucose, but a negative correlation (P < 0.05) with MoCA score. This negative relationship remained (P < 0.05) after adjusting various covariates, and was found to be mediated (P < 0.05) by serum ox-LDL. In conclusion, our results reveal serum ox-LDL as a potential mediator for the inverse relationship between the elevation of serum d-ribose concentration and the decline of cognitive performance in the T2DM-MCI patients.

Oxidative status in plasma, urine and saliva of girls with anorexia nervosa and healthy controls: a cross-sectional study

BackgroundAnorexia nervosa (AN) is a serious psychosomatic disorder with unclear pathomechanisms. Metabolic dysregulation is associated with disruption of redox homeostasis that might play a pivotal role in the development of AN. The aim of our study was to assess oxidative status and carbonyl stress in plasma, urine and saliva of patients with AN and healthy controls.MethodsPlasma, spot urine, and saliva were collected from 111 girls with AN (aged from 10 to 18 years) and from 29 age-matched controls. Markers of oxidative stress and antioxidant status were measured using spectrophotometric and fluorometric methods.ResultsPlasma advanced oxidation protein products (AOPP) and advanced glycation end products (AGEs) were significantly higher in patients with AN than in healthy controls (by 96, and 82%, respectively). Accordingly, urinary concentrations of AOPP and fructosamines and salivary concentrations of AGEs were higher in girls with AN compared with controls (by 250, and 41% in urine; by 92% in saliva, respectively). Concentrations of thiobarbituric acid reactive substances (TBARS) in saliva were 3-times higher in the patients with AN than in the controls. Overall antioxidants were lower in plasma of girls with AN compared to the controls, as shown by total antioxidant capacity and ratio of reduced and oxidized glutathione (by 43, and 31%, respectively).ConclusionsThis is the first study assessing wide range of markers of oxidative status in plasma, urine and saliva of the patients with AN. We showed that both, higher levels of markers of oxidative stress and lower antioxidants play a role in redox disruption. Restoration of redox homeostasis might be of the clinical relevance

POS-373 Advanced oxidation protein products activate oxidative stress in vitro via soluble (pro)renin receptor mediated intrarenal renin angiotensin system and Nox4/H2O2 pathway

Advanced oxidation protein products (AOPPs) are newly identified as a novel oxidative stress biomarkers. Previous research has indicated potential associations between AOPPs and activation intrarenal local renin angiotensin system (RAS). However, no known empirical research has focused on exploring relationships between AOPPs and the new member of RAS, (pro) renin receptor (PRR). Aim of this study was to test the role of soluble PRR (sPRR) in AOPPs-induced oxidative stress responses in cultured human renal proximal tubular cell line HK-2 cells. The HK-2 cells were incubated for 24h in the presence of different concentrations of AOPPs, or incubated for different time lengths in the presence of 100 μg/ml of AOPPs. In HK-2 cells treated with PRO20, furin inhibitors, GM6001, PF-429242, sPRR-His, or transfected with PRR siRNA, site-1 protease (S1P) siRNA, Nox4 siRNA prior to exposure to AOPPs, the changes in the protein expressions of PRR/sPRR and Nox4 were examined with Western blotting, mRNA lelvels of PRR, angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), angiotensinogen (AGT), intercellular adhesion molecule (ICAM1), tumor necrosis factor-α (TNF-α) by using real-time quantitative PCR, the cell medium for renin activity, ACE activity, sPRR, Ang II, H2O2, thiobarbituric acid reactive substances (TBARS) concentrations by using ELISA Assay kits. AOPPs showed time-dependent and dose-independent effects on PRR cleavage produces sPRR. AOPP-albumin treatment induced a >4-times increase in medium sPRR due to enhanced cleavage of PRR but unmodified albumin has no effect. Inhibition of S1P with PF-429242 or siRNA remarkably suppressed AOPPs-induced sPRR production. Surprisingly, this cleavage event was unaffected by inhibition of furin or ADAM19. AOPPs (100 μg/ml) treatment for 24 h induced renin activity and oxidative stress, both of which were attenuated by a PRR decoy inhibitor PRO20 and S1P inhibitor PF429242. What’s more, PF-429242 significantly decreased AOPPs stimulated Nox4 and H2O2 expression and administration of a recombinant sPRR, termed sPRR-His, reversed the effects of S1P inhibition. Taken together, these findings suggest that AOPPs induce oxidative stress via S1P-derived soluble (pro)renin receptor activation intrarenal renin angiotensin system and Nox4/H2O2 pathway in vitro.