Biomarker Of Oxidative Damage Research Articles

Cross-sectional and longitudinal associations of PAHs exposure with serum uric acid and hyperuricemia among Chinese urban residents: The potential role of oxidative damage

A few studies found polycyclic aromatic hydrocarbons (PAHs) were associated with serum uric acid (SUA) or hyperuricemia (HUA). However, the longitudinal study is vacant, and the underlying mechanisms remain unclear. We aimed to assess the cross-sectional and longitudinal associations of urinary PAHs metabolites with SUA levels and HUA risk, and explore the mediating effects of oxidative stress and inflammation. 10 urinary mono-hydroxylated PAHs metabolites and SUA levels were measured among 4047 Chinese urban residents at baseline and 1496 individuals at 6-year follow-up. Biomarkers of oxidative damage and inflammation in urine/plasma were determined at baseline. We adopted generalized linear mixed models and logistic regression to assess the associations of PAHs metabolites with SUA and HUA, weighted quantile sum regression and adaptive elastic net regression to evaluate the overall effects of multi-PAHs mixture, and mediation analysis to estimate the mediating roles of the biomarkers. In the cross-sectional study, each 1-unit increase in the ln-transformed values of 2-OHNa, 2-OHFlu, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 4.10-, 3.90-, 6.42-, 7.33-, 4.85-, 5.43-, 4.47-, 7.67-, and 5.22-μmol/L increase in SUA, respectively. Meanwhile, each 1-unit increase in the ln-transformed values of 1-OHNa, 2-OHNa, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 17, 14, 15, 22, 14, 19, 18, 27, and 21% increment in HUA risk, respectively. After 6 years, individuals with persistent high level of 9-OHPh had a 12.5 μmol/L increase in SUA compared with those with persistent low level. The overall effects of multi-PAHs mixture on SUA and HUA remain positive. 8-hydroxy-deoxyguanosine mediated the associations of PAHs metabolites with SUA and HUA, and the mediated proportion ranged from 5.39% to 15.34%. PAHs exposure was associated with the elevated SUA levels and increased HUA risk, and oxidative DNA damage may be one of the underlying mechanisms.

Toxicological insight of metiram: immuno-oxidative, neuro-behavioral, and hemato-biochemical changes during acute exposure of Nile tilapia (Oreochromis niloticus)

BackgroundThe inappropriate use of pesticides including fungicides creates severe biological hazards that can endanger fish health and impede sustainable aquaculture.ObjectiveThis study investigated the negative impacts of metiram (MET), a fungicide on the health status of Nile tilapia (Oreochromis niloticus) for a 96-hour duration as an acute exposure in a static renewal system.MethodsThree hundred fish (average body weight: 37.50 ± 0.22 g) were assigned into six groups (50 fish/group) with five replicates (10 fish/replicate). Fish were exposed to various six concentrations (0, 1.5, 3, 4.5, 6, and 7.5 mg/L) of MET as a water exposure to for 96-hour without water exchange. The fish’s behavior, clinical signs, and mortalities were documented every day of the exposure period. Additionally, MET’s impact on blood profile, stress biomarkers, hepato-renal functions, immune-antioxidant status, and brain biomarker were closely monitored.ResultsThe lethal concentration (LC50) of MET estimated using Finney’s probit technique was 3.77 mg/L. The fish’s behavior was severely impacted by acute MET exposure, as clear by an increase in surfacing, loss of equilibrium, unusual swimming, laterality, abnormal movement, and a decline in aggressive behaviors. The survivability and hematological indices (white and red blood cell count, differential white blood cell count, hematocrit value, and hemoglobin) were significantly reduced in a concentration-dependent manner following MET exposure. Acute exposure to MET (1.5–7.5 mg/L) incrementally increased stress biomarkers (nor-epinephrine, cortisol, and glucose), lipid peroxides (malondialdehyde), and brain oxidative DNA damage biomarker (8-hydroxy-2-deoxyguanosine). A hepato-renal dysfunction by MET exposure (4.5–7.5 mg/L) was evidenced by the significant increase in the alanine and aspartate aminotransferases and creatinine values. Moreover, a substantial decline in the immune parameters (lysozyme, complement 3, serum bactericidal activity, and antiprotease activity) and antioxidant variables (total antioxidant capacity, superoxide dismutase, and glutathione peroxidase) resulted from acute MET exposure.ConclusionAccording to these findings, the 96-hour LC50 of MET in Nile tilapia was 3.77 mg/L. MET exposure triggered toxicity in Nile tilapia, as seen by alterations in fish neuro-behaviors, immune-antioxidant status, hepato-renal functioning, and signifying physiological disturbances. This study emphasizes the potential ecological dangers provoked by MET as an environmental contaminant to aquatic systems. However, the long-term MET exposure is still needed to be investigated.

Donor-Dependent Variations in Systemic Oxidative Stress and Their Association with One-Year Graft Outcomes in Kidney Transplantation.

Oxidative stress has been implicated in complications after kidney transplantation (KT), including delayed graft function (DGF) and rejection. However, its role in long-term posttransplant outcomes remains unclear. We investigated oxidative damage and antioxidant defense dynamics, and their impact on the graft outcomes, in 41 KT recipients categorized by type of donation over 12 months. Oxidative status was determined using OxyScore and AntioxyScore indexes, which comprise several circulating biomarkers of oxidative damage and antioxidant defense. Donor types included donation after brain death (DBD [61.0%]), donation after circulatory death (DCD [26.8%]), and living donation (LD [12.1%]). There was an overall increase in oxidative damage early after transplantation, which was significantly higher in DCD as compared to DBD and LD recipients. The multivariate adjustment confirmed the independent association of OxyScore and type of deceased donation with DGF, donor kidney function, and induction therapy with antithymocyte globulin. There were no differences in terms of antioxidant defense. Lower oxidative damage at day 7 predicted better graft function at 1-year posttransplant only in DBD recipients. DCD induced greater short-term oxidative damage after KT, whereas the early levels of oxidative damage were predictive of the graft function 1 year after KT among DBD recipients.

#2432 DNA damage analysis with oxidative stress index in patients developing contrast nephropathy after coronary angiography

Abstract Background and Aims Contrast Nephropathy (KN) is acute kidney injury that occurs after exposure to contrast material. Advanced age, chronic kidney disease, heart failure, anemia, hypertension, diabetes mellitus, and hyperuricemia have been reported in the literature to increase the risk of KN development. In addition, oxygen radicals have an important place in the pathogenesis of contrast nephropathy development. Specific biomarkers are used in clinics to determine oxidative stress and antioxidant status. In particular, measurement of total antioxidant status (TAS) and total oxidant status (TOS) can provide useful information about an individual's overall serum antioxidative status. The ratio of TOS to TAS level gives the oxidative stress index (OSI). One of the most investigated metabolites for DNA damage is 8-hydroxy-2-deoxyguanosine (8-OhdG), which is accepted as a biomarker of oxidative damage to DNA. In our study, we planned to investigate DNA damage and important predisposing factors for contrast nephropathy using oxidative stress markers. Method Between February 2021 and April 2022, blood was taken from 191 patients who underwent coronary angiography (CAG) by the Cardiology Department at ESOGU before CAG and at 72 hours after CAG. Patients who met the criteria for contrast nephropathy development (those with a serum creatinine increase of 25% or more compared to baseline or an increase of 0.5 mg/dl or more) were included as the case group in our study. Our study is a prospective study consisting of 85 cases and 106 controls, totaling 191 participants. TAS, TOS, OSI, and 8-OhDG levels were compared between both groups and before-after procedure. This study was supported by ESOGU BAP project number 1621. Results The mean age of the developing group was calculated as 68.13 ± 10.37, while it was calculated as 61.03 ± 9.97 in the control group (p = 0.00). In the case group, there were 30 (35.3%) without heart failure, while there were 75 (70.8%) without heart failure in the control group (p = 0.00). In univariate analyzes, we found that advanced age and heart failure were the most important indicators for KMN. When we compared those with and without KMN, we saw that TOS values decreased less in the group with post-angiography nephropathy than in those without it. We found a positive correlation between uric acid and TAS. In the KMN group, it was found that there was a statistically significant increase in TAS value after CAG, while there was a decrease in OSI value, and no statistically significant difference was found for TOS and 8-OhDG. In patients who underwent percutaneous intervention, it was found that there was a statistically significant increase in TAS value after CAG, while TOS and OSI decreased, and no significant difference was found for 8-OhDG. Conclusion Although previous studies have shown that oxidative stress plays an important role in contrast nephropathy pathogenesis, a strong relationship between KMN development and oxidative stress could not be found in our study. Our study is the first study to examine DNA damage with 8-OhDG in KMN, and it has been shown that there is no increase in DNA damage with KMN development. It is thought that one of the reasons leading to this result may be that contrast agents used today are selected as less toxic substances used in less volumes during processing, which may prevent DNA damage from occurring. Another result reached in our study is that TAS level increased in patients undergoing percutaneous intervention, while TOS and OSI decreased; that is, revascularization can reduce TOS and ultimately oxidative status.”

Captopril's influence on Danio rerio embryonic development: Unveiling significant toxic outcomes at environmentally relevant concentrations

Anticipating a global increase in cardiovascular diseases, there is an expected surge in the use of angiotensin-converting enzyme inhibitors, notably captopril (CAP). This heightened usage raises significant environmental apprehensions, mainly due to limited knowledge regarding CAP's toxic effects on aquatic species. In response to these concerns, the current study aimed to tackle this knowledge gap by evaluating the potential influence of nominal concentrations of CAP (0.2–2000 μg/L) on the embryonic development of Danio rerio. The findings revealed that CAP at all concentrations, even at concentrations considered environmentally significant (0.2 and 2 μg/L), induced various malformations in the embryos, ultimately leading to their mortality. Main malformations included pericardial edema, craniofacial malformation, scoliosis, tail deformation, and yolk sac deformation. In addition, CAP significantly altered the antioxidant activity of superoxide dismutase and catalase across all concentrations. Simultaneously, it elevated lipid peroxidation levels, hydroperoxides, and carbonylic proteins in the embryos, eliciting a substantial oxidative stress response. Likewise, CAP, at all concentrations, exerted significant modulatory effects on the expression of genes associated with apoptosis (bax, bcl2, p53, and casp3), organogenesis (tbx2a, tbx2b, and irx3b), and ion exchange (slc12a1 and kcnj1) in Danio rerio embryos. Both augmentation and reduction in the expression levels of these genes characterized this modulation. The Pearson correlation analysis indicated a close association between oxidative damage biomarkers and the expression patterns of all examined genes with the elevated incidence of malformations and mortality in the embryos. In summary, it can be deduced that CAP poses a threat to aquatic species. Nevertheless, further research is imperative to enhance our understanding of the environmental implications of this pharmaceutical compound.

The halotolerant white sea anemone Anthothoe chilensis, highly abundant in brine discharges zones, as a promising biomonitoring species for evaluating the impacts of desalination plants

Seawater desalination raises concerns about its environmental repercussions, particularly the impact of brine discharge on benthic communities. In this study, we evaluated the effects of desalination and artificial brines on the sea anemone Anthothoe chilensis, following its observed proliferation near a brine outfall from a Chilean desalination plant. We measured biomarkers for oxidative stress (ROS content, lipid peroxidation, and protein carbonylation), antioxidant response (thiols), and osmotic stress (free amino acids and proline) in individuals collected from a brine discharge pipe (∼56 psu) and compared them to a population living in natural seawater salinity. Additionally, we conducted controlled laboratory experiments where A. chilensis specimens were exposed to a control salinity of 33 psu and to elevated salinities of 37 and 42 psu for 24 and 48 h. Results revealed a significant decrease in oxidative damage biomarkers, such as protein carbonylation and ROS content, along with an increase in free amino acids, proline, and thiols content at higher salinity levels, particularly under controlled conditions. These findings demonstrate the remarkable efficient cellular stress responses of this highly halotolerant species, which could potentially promote risky A. chilensis blooms in brine discharges areas. Additionally, this study provides valuable biomarker information for assessing the short-term impacts of brine discharges, which can be used in biomonitoring programs within the desalination sector.

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.

Performance, HSP70 expression, antioxidant enzymes, oxidative DNA damage biomarkers, metabolic hormones, and intestinal microbiota of broiler chickens fed mistletoe leaf powder supplemented diets under tropical high ambient temperatures

The study investigated the impact of Mistletoe Leaf Powder (MLP) supplementation on some parameters in heat-stressed broiler chickens. The standard baseline diets, comprising four different formulations, were provided during the starter and finisher stages. Chickens were randomly assigned to the 4 dietary groups: a negative control (CON) with no supplementation, a positive control (VTC) with 200 mg/kg vitamin C, and 2 experimental treatment groups with 2500 mg/kg (MLP2) and 5000 mg/kg (MLP5) MLP supplementation. The Body Weight Gain (BWG) in MLP2 and MLP5 treatment groups was comparable (P > 0.05) to those in VTC, while the CON group exhibited significantly (P < 0.05) lower BWG. Feed consumption was significantly (P < 0.05) lower broiler chickens in the CON group compared to those VTC, MLP2, and MLP5. Heat shock protein 70 (HSP70) levels were lower in broiler chickens belonging to VTC, MLP2, and MLP5 groups compared to those in CON, and MLP2 showed no difference (P > 0.05) from MLP5 and VTC. Serum glutathione peroxidase and catalase concentrations were higher (P < 0.05) in birds belonging to MLP5, MLP2, and VTC groups compared to CON. The 8-hydroxy-2′-deoxyguanosine concentration was lower (P < 0.05) in birds of VTC, MLP2, and MLP5 compared to the CON, with VTC showing the least concentration. Serum insulin levels were higher (P < 0.05) in MLP5 compared to those in CON, while serum triiodothyronine and leptin concentrations were lower (P < 0.05) in CON compared to birds in VTC, MLP2, and MLP5. Microbiota analysis revealed that the Coliform bacteria population was higher (P < 0.05) in birds belonging to CON compared to those in VTC, MLP2, and MLP5 groups, whereas lactic acid-producing bacteria were significantly (P < 0.05) lower in birds of CON and highest in MLP2 and MLP5 groups. In conclusion, dietary supplementation of MLP at 5000 mg/kg enhanced performance, oxidative status, influenced metabolic hormones, and gut microbiota in broiler chickens raised under high ambient temperature.

Hyperbaric Oxygen Reduces Oxidative Stress Impairment and DNA Damage and Simultaneously Increases HIF-1α in Ischemia-Reperfusion Acute Kidney Injury.

The central exacerbating factor in the pathophysiology of ischemic-reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a result of postischemic AKI. γH2AX(S139) histone has been identified as a potentially useful biomarker of DNA DSBs. On the other hand, hypoxia-inducible factor (HIF) is the "master switch" for hypoxic adaptation in cells and tissues. The aim of this research was to evaluate the influence of hyperbaric oxygen (HBO) preconditioning on antioxidant capacity estimated by FRAP (ferric reducing antioxidant power) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, as well as on oxidative stress parameter 3-nitrotyrosine, and to assess its effects on γH2AX(S139), HIF-1α, and nuclear factor-κB (NF-κB) expression, in an experimental model of postischemic AKI induced in spontaneously hypertensive rats. The animals were divided randomly into three experimental groups: sham-operated rats (SHAM, n = 6), rats with induced postischemic AKI (AKI, n = 6), and group exposed to HBO preconditioning before AKI induction (AKI + HBO, n = 6). A significant improvement in the estimated glomerular filtration rate, eGFR, in AKI + HBO group (p < 0.05 vs. AKI group) was accompanied with a significant increase in plasma antioxidant capacity estimated by FRAP (p < 0.05 vs. SHAM group) and a reduced immunohistochemical expression of 3-nitrotyrosine and γH2AX(S139). Also, HBO pretreatment significantly increased HIF-1α expression (p < 0.001 vs. AKI group), estimated by Western blot and immunohistochemical analysis in kidney tissue, and decreased immunohistochemical NF-κB renal expression (p < 0.01). Taking all of these results together, we may conclude that HBO preconditioning has beneficial effects on acute kidney injury induced in spontaneously hypertensive rats.

Targeting SIRT1, NLRP3 inflammasome, and Nrf2 signaling with chrysin alleviates the iron-triggered hepatotoxicity in rats

Blood transfusion-requiring diseases such as sickle cell anemia and thalassemia are characterized by an imbalance between iron intake and excretion, resulting in an iron overload (IOL) disorder. Hepatotoxicity is prevalent under the IOL disorder because of the associated hepatocellular redox and inflammatory perturbation. The current work was devoted to investigate the potential protection against the IOL-associated hepatotoxicity using chrysin, a naturally-occurring flavone. IOL model was created in male Wistar rats by intraperitoneal injection of 100 mg/kg elemental iron subdivided on five equal injections; one injection was applied every other day over ten days. Chrysin was administered in a daily dose of 50 mg/kg over the ten-day iron treatment period. On day eleven, blood and liver samples were collected and subjected to histopathological, biochemical, and molecular investigations. Chrysin suppressed the IOL-induced hepatocellular damage as revealed by decreased serum activity of the intracellular liver enzymes and improved liver histological picture. Oxidative damage biomarkers, and pro-inflammatory cytokines were significantly suppressed. Mechanistically, the levels of the redox and inflammation-controlling proteins SIRT1 and PPARγ were efficiently up-regulated. The liver iron load, NLRP3 inflammasome activation, and NF-κB acetylation and nuclear shift were significantly suppressed in the iron-intoxicated rats. Equally important, the level of the antioxidant protein Nrf2 and its target HO-1 were up-regulated. In addition, chrysin significantly ameliorated the IOL-induced apoptosis as indicated by reduction in caspase-3 activity and modulation of BAX and Bcl2 protein abundance. Together, these findings highlight the alleviating activity of chrysin against the IOL-associated hepatotoxicity and shed light on the role of SIRT1, NLRP3 inflammasome, and Nrf2 signaling as potential contributing molecular mechanisms.

Protective Effect of Quercetin against Paraquat-induced Brain Mitochondrial Disruption in Mice.

Paraquat is a highly toxic quaternary ammonium herbicide widely used in agriculture. It is an agent that induces pulmonary toxicity via the redox cyclic reaction. The present study investigated the protective effect of quercetin against paraquatinduced brain mitochondria disruption in mice. Paraquat (1.25 mg/kg, intraperitoneally) was administered to the mice, and then quercetin (50, 100, 200 mg/kg) was injected i.p. Oxidative damage biomarkers such as reactive oxygen species, protein carbonyl, lipid peroxidation, glutathione content, and mitochondrial function were assessed in the brain mitochondria. The results showed that paraquat significantly (P < 0.001) increased the reactive oxygen species, protein carbonyl, and lipid peroxidation and significantly (P < 0.0001) decreased the glutathione content and mitochondrial function in the brain cells. Administration of the quercetin at doses of 50, 100, and 200 mg/kg significantly reduced reactive oxygen species, lipid peroxidation, and protein carbonyl and improved mitochondrial function and glutathione content in the mice brain mitochondrial compared to the paraquat group. Quercetin at 200 mg/kg dose had better effectiveness than 50 and 100 mg/kg doses. Our results suggest that quercetin in a dose-dependent manner has neuroprotective effects, probably by free radicals scavenging or enhancing the antioxidant mechanisms in the brain mitochondria. It seems that quercetin could modulate protein and lipid oxidation and improve oxidative damage induced by paraquat in the early stages.

Elucidating the effects of pure glyphosate and a commercial formulation on early life stages of zebrafish using a complete biomarker approach: All-or-nothing!

The search for new methods in the toxicology field has increased the use of early life stages of zebrafish (Danio rerio) as a versatile organism model. Here, we use early stages of zebrafish to evaluate glyphosate as pure active ingredient and within a commercial formulation in terms of oxidative stress. Biomarkers involved in the oxidative status were evaluated along with other markers of neurotoxicity, genotoxicity, cytotoxicity, energy balance and motor performance, and the selected tools were evaluated by its sensitivity in determining early-warning events. Zebrafish embryos exposed to glyphosate active ingredient and glyphosate-based formulation were under oxidative stress, but only the commercial formulation delayed the embryogenesis, affected the cholinergic neurotransmission and induced DNA damage. Both altered the motor performance of larvae at very low concentrations, becoming larvae hypoactive. The energy balance was also impaired, as embryos under oxidative stress had lower lipids reserves. Although data suggest that glyphosate-based formulation has higher toxicity than the active ingredient itself, the most sensitive biomarkers detected early-warning effects at very low concentrations of the active ingredient. Biochemical biomarkers of defense system and oxidative damage were the most sensitive tools, detecting pro-oxidant responses at very low concentrations, along with markers of motor performance that showed high sensitivity and high throughput, suitable for detecting early effects linked to neurotoxicity. Alterations on morphology during embryogenesis showed the lowest sensitivity, thus morphological alterations appeared after several alterations at biochemical levels. Tools evaluating DNA damage and cell proliferation showed mid-sensitivity, but low throughput, thus they could be used as complementary markers.

Measurement of 8-hydroxy-2'-deoxyguanosine in serum and cerebrospinal fluid of horses with neuroaxonal degeneration and other causes of proprioceptive ataxia.

Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses. We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses. Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November 2010 and March 2022. Case-control study using biobanked samples was performed and commercial competitive ELISA kit (Highly Sensitive 8-OHdG Check ELISA) utilized. Concentration of 8-OHdG was quantitated in both CSF and serum and compared between groups. No correlation was established between the measures of 8-OHdG in serum and CSF and group. CSF median [8-OHdG] for NAD/DM was 169.9 pg/mL (IQR25-75 : 67.18-210.6), CVSM 157.1 pg/mL (IQR25-75 : 132.1-229.1), EPM 131.4 pg/mL (IQR25-75 : 102.1-193.2), and control 149.8 pg/mL (IQR25-75 : 113.3-196.4). Serum median [8-OHdG] for NAD/DM was 130 pg/mL (IQR25-75 : 51.73-157.2), CVSM 125.8 pg/mL (IQR25-75 : 62.8-170.8), EPM 120.6 pg/mL (IQR25-75 : 87.23-229.7), and control 157.6 pg/mL (IQR25-75 : 97.15-245.6). Poisson regression analysis showed no difference established once confounding variables were considered. Eight-OHdG did not aid in antemortem diagnosis of NAD/DM in this cohort of horses. At the time of diagnosis horses with NAD/DM do not have ongoing oxidative stress.

Identification of novel F2-isoprostane metabolites by specific UDP-glucuronosyltransferases

UDP-glucuronosyltransferases (UGTs) catalyze the conjugation of glucuronic acid with endogenous and exogenous lipophilic small molecules to facilitate their inactivation and excretion from the body. This represents approximately 35 % of all phase II metabolic transformations. Fatty acids and their oxidized eicosanoid derivatives can be metabolized by UGTs. F2-isoprostanes (F2-IsoPs) are eicosanoids formed from the free radical oxidation of arachidonic acid. These molecules are potent vasoconstrictors and are widely used as biomarkers of endogenous oxidative damage. An increasing body of evidence demonstrates the efficacy of measuring the β-oxidation metabolites of F2-IsoPs rather than the unmetabolized F2-IsoPs to quantify oxidative damage in certain settings. Yet, the metabolism of F2-IsoPs is incompletely understood. This study sought to identify and characterize novel phase II metabolites of 15-F2t-IsoP and 5-epi-5-F2t-IsoP, two abundantly produced F2-IsoPs, in human liver microsomes (HLM). Utilizing liquid chromatography-mass spectrometry, we demonstrated that glucuronide conjugates are the major metabolites of these F2-IsoPs in HLM. Further, we showed that these molecules are metabolized by specific UGT isoforms. 15-F2t-IsoP is metabolized by UGT1A3, 1A9, and 2B7, while 5-epi-5-F2t-IsoP is metabolized by UGT1A7, 1A9, and 2B7. We identified, for the first time, the formation of intact glucuronide F2-IsoPs in human urine and showed that F2-IsoP glucuronidation is reduced in people supplemented with eicosapentaenoic and docosahexaenoic acids for 12 weeks. These studies demonstrate that endogenous F2-IsoP levels can be modified by factors other than redox mechanisms.

Exploring 8-hydroxy-2-deoxyguanosine as a biomarker of oxidative DNA damage in various diseases and pathological conditions: Review

Exploring 8-hydroxy-2-deoxyguanosine as a biomarker of oxidative DNA damage in various diseases and pathological conditions: Review

Influence of Body Mass Index on the Markers of Inflammation and Oxidative Stress among Young Females during Menstrual Cycle

Background: Fluctuating levels of biomarkers of inflammation and oxidative damage are observed during different phases of the menstrual cycle. Recent studies suggest an involvement of oxidative stress (OS) and inflammation in the development of Polycystic ovary syndrome (PCOS). As obesity increases the risk of PCOS, the present study aims to compare these biomarkers among young females across different Body Mass Index (BMI) groups. Objectives: To determine variations in the concentrations of Malondialdehyde (MDA) and Total Antioxidant Capacity (TAC) as biomarkers of oxidative stress, and high sensitivity C-reactive protein (hs-CRP) as a biomarker of inflammation, and compare among normal and obese young females during the phases of menstrual cycle. Methods:The study included 37 females (20 normal and 17 obese) aged 18 – 22 years. Serum analysis for hs-CRP, MDA, and TAC were performed. Paired and Independent sample T-tests were appropriately used comparing the parameters between early follicular (EFP) and mid-luteal phase (MLP) among the normal and obese subjects. Results: Significant differences were seen in the concentrations of hs-CRP, MDA, and TAC during EFP and MLP of the menstrual cycle among the normal and obese females. An elevated concentration of hs-CRP and MDA, and reduced TAC were observed in the obese compared to normal throughout the menstrual cycle. More than 82.5% of obese subjects having the hs-CRP above normal is alarming, increasing their risk of future CVD and PCOS. Conclusion: Our findings warrant clinical evaluation with prevention strategies for our obese young females. Also, the findings recommend future elaborate research including various biological parameters connected to inflammation and oxidative stress, resolving the etiology of hormonal disorders causing reproductive issues like PCOS in women.

Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina.

Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage, which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested to be more sensitive and specific for imaging spectral characteristics of lipofuscin fluorescence.

Arsenic exposure and oxidative damage to lipid, DNA, and protein among general Chinese adults: A repeated-measures cross-sectional and longitudinal study

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2′-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (β: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.

Ameliorative effects of Sida acuta and vitamin C on serum DNA damage, pro-inflammatory and anti-inflammatory cytokines in roosters fed aflatoxin B1 contaminated diets

The ameliorative effects of Sida acuta leaf meal (SALM) and vitamin C on the serum pro-inflammatory and anti-inflammatory cytokines as well as DNA damage of cocks fed aflatoxin B1 (AFB1) contaminated diets were examined. The experiment was a completely randomized design with a total of 250 sexually mature Isa White cocks aged 24 weeks, randomly allotted into five experimental diets; each diet contained 5 replicates with 10 roosters. The diets were A (control/basal diet), B (A + 1 mg/kg AFB1), C (B + 200 mg/kg vitamin C), D (B + 2.5 g/kg SALM) and E (B + 5.0 g/kg SALM). Fresh and clean water was also provided for the whole experimental period of twelve weeks. Inclusion of 1 mg/kg AFB1 without vitamin C or SALM increased TNF-α and IL-1β as well as 8-OHdG and NF-κB in the serum significantly (P < 0.05) among the cocks on diet B. However, the fortification of AFB1 contaminated diets with vitamin C and SALM depressed serum TNF-α, IL-1β, 8-OHdG and NF-κB concentrations of the cocks significantly (P < 0.05). Conversely, serum IL-4 and IL-10 in birds given 1 mg/kg AFB1 without vitamin C or SALM decreased significantly (P < 0.05) in comparison with the roosters on the control. However, improvements (P < 0.05) in IL-4 and IL-10 concentrations with corresponding reduction (P < 0.05) in TNF-α, IL-1β, 8-OHdG and NF-κB concentrations were recorded among cocks fed Diets C, D and E, respectively. Therefore, dietary addition of SALM at the level used in this study was beneficial and has comparable effects with inorganic antioxidant (C vitamin) by significantly reducing the inflammatory cytokines and oxidative damage biomarkers as well as enhancing the anti-inflammatory cytokines thereby promoting the health status of the cocks fed AFB1 contaminated ration.

Origanum majorana Essential Oil Ameliorated the Behavioral, Biochemical, Physiological and Performance Perturbations Induced by Aflatoxin B1 in Growing Rabbits

Abstract The current study assessed the benefits of marjoram essential oil (MEO) in reducing the aflatoxin B1 (AFB1) toxicity in growing rabbits. Forty-eight rabbits, aged 4 weeks, were randomly assigned to four groups (4 replications of 3 rabbits/replicate) as follows: BD group (control); AFB1 group (supplemented with AFB1 0.3 mg/kg diet); MEO-supplemented group (1 g MEO/kg diet); AFB1 + MEO group (AFB1 0.3 mg/kg diet + 1 g MEO/kg diet). AFB1 exposure resulted in reduction of rabbit growth and total protein and albumin content in serum; increased liver function related enzymes (ALP, ALT and AST); induced oxidative stress displayed by lower level of antioxidant enzymes (CAT and GSH), increased biomarkers of DNA and lipid oxidative damage with significant upregulation of the tumor suppressor protein interferon-γ, interleukin 1β, tumor necrosis factor-α and heat shock protein-70 when compared to the control (P&lt;0.05). Moreover, exposure to AFB1 increased the bioaccumulation of AFB1 residues in rabbit liver. Supplementation of MEO in the AFB1-exposed rabbits alleviated all of its negative effects. In conclusion, dietary addition of 1 g MEO could effectively ameliorate the adverse impacts of AFB1 on rabbit growth; enhanced their antioxidants and reduced oxidative stress and inflammatory response indicators, as well as the AFB1 residues in liver.