Deoxyguanosine Levels Research Articles

3,5-Dihydroxy-4-methoxybenzyl alcohol, a novel antioxidant isolated from oyster meat, inhibits the hypothalamus–pituitary–adrenal axis to regulate the stress response

BackgroundAntioxidants that can scavenge reactive oxygen in the brain and inhibit hyperactivity of the HPA axis are desirable. AimsWe investigated the cerebral translocation of the antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) and the effects of DHMBA administration on the hypothalamus–pituitary–adrenal (HPA) axis in stress-loaded rats. MethodsExperiment 1: Plasma and brain DHMBA concentrations were measured over time after oral DHMBA administration to male B6 mice. Experiment 2: Female Wistar Imamichi rats were used. The normal group was not subjected to stress. The stress, DHMBA, and vitamin E groups were subjected to individual and overcrowding stress. Brain and hippocampal 8-hydroxy-2′-deoxyguanosine levels, hippocampal glucocorticoid receptor-α levels, plasma corticosterone levels and RNA levels of glutathione peroxidase 4, catalase, and glutathione reductase in the hippocampus were measured. ResultsIn Experiment 1, DHMBA was not detected in the plasma or brain before DHMBA administration but was detected in both after administration. In Experiment 2, brain and hippocampal 8-hydroxy-2′-deoxyguanosine levels and plasma corticosterone levels were significantly lower in the DHMBA than in the stress group. Glucocorticoid receptor-α levels were higher in the DHMBA than in the stress group. DHMBA increased RNA levels of antioxidant enzymes in the hippocampus. Conclusion: DHMBA was translocated to the brain after administration. DHMBA administration decreased 8-hydroxy-2′-deoxyguanosine levels in the brain and hippocampus, increased hippocampal glucocorticoid receptor-α levels, and decreased the plasma corticosterone concentration, suggesting that DHMBA inhibits hyperactivity of the HPA axis. Nrf2 pathway activity induced by DHMBA resulted in increased antioxidant enzyme levels in the hippocampus.

Detrimental effects of glyphosate on muscle metabolism in grass carp (Ctenopharyngodon idellus)

Glyphosate, a commonly used herbicide, has been associated with environmental pollution and potential health risks to aquatic organisms. This study investigated the effects of glyphosate on the muscle metabolism of grass carp (Ctenopharyngodon idellus) following exposure to environmentally relevant concentrations. Over a 14-day exposure period to varying glyphosate levels, significant disruptions were observed in antioxidant capacity and muscle health. These disruptions were evidenced by reductions in total antioxidant capacity (T-AOC), increases in malondialdehyde (MDA) levels, and decreases in activities of glutathione peroxidase (GSH-PX) and catalase (CAT). Furthermore, exposure to glyphosate resulted in a reduction of vitamin E content and an elevation of hormonal levels, suggesting the potential for endocrine disruption. Metabolomics analysis identified 605 distinct metabolites, with notable alterations in amino acid, carbohydrate, and nucleotide metabolism pathways. Specifically, arginine and glutathione metabolisms were severely impacted, with decreases in key amino acids such as glycine and glutathione at higher glyphosate concentrations. Nucleotide metabolism, particularly purine synthesis, was also significantly affected, with reduced levels of deoxyguanosine and other purine-related compounds. The study further investigated the origins of these differential metabolites using the MetOrigin platform, suggesting a potential involvement of the intestinal microbiota in the metabolic response to glyphosate. These findings highlight the multifaceted adverse effects of glyphosate on fish muscle, including oxidative stress and metabolic dysregulation, which may contribute to diminished muscle quality and health risks for aquatic organisms.

Methylation alterations of imprinted genes in different placental diseases

BackgroundImprinted genes play important functions in placentation and pregnancy; however, research on their roles in different placental diseases is limited. It is believed that epigenetic alterations, such as DNA methylation, of placental imprinting genes may contribute to the different pathological features of severe placental diseases, such as pre-eclampsia (PE) and placenta accreta spectrum disorders (PAS).ResultsIn this study, we conducted a comparative analysis of the methylation and expression of placental imprinted genes between PE and PAS using bisulfite sequencing polymerase chain reaction (PCR) and quantitative PCR, respectively. Additionally, we assessed oxidative damage of placental DNA by determining 8-hydroxy-2′-deoxyguanosine levels and fetal growth by determining insulin-like growth factor 2 (IGF2) and cortisol levels in the umbilical cord blood using enzyme-linked immunosorbent assay. Our results indicated that methylation and expression of potassium voltage-gated channel subfamily Q member 1, GNAS complex locus, mesoderm specific transcript, and IGF2 were significantly altered in both PE and PAS placentas. Additionally, our results revealed that the maternal imprinted genes were significantly over-expressed in PE and significantly under-expressed in PAS compared with a normal pregnancy. Moreover, DNA oxidative damage was elevated and positively correlated with IGF2 DNA methylation in both PE and PAS placentas, and cortisol and IGF2 levels were significantly decreased in PE and PAS.ConclusionsThis study suggested that DNA methylation and expression of imprinted genes are aberrant in both PE and PAS placentas and that PE and PAS have different methylation profiles, which may be linked to their unique pathogenesis.

Exposure of Cattle Breeding Herds to Naturally Co-Contaminated Zearalenone and Deoxynivalenol: The Relevance of a Urinary Mycotoxin Monitoring System for Herd Health and Food Safety.

The widespread presence of Fusarium mycotoxins in animal feed is a global issue, not only for the health of livestock but also for ensure the safety of food as an end product. High concentrations of zearalenone (ZEN) and deoxynivalenol (DON) have been detected in the diets of Japanese Black (JB) and Holstein Friesian (HF) breeding herds. Consequently, we monitored serum biochemical parameters over a long time in both herds, focusing on anti-Müllerian hormone (AMH) levels and acute-phase inflammation. Additionally, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and progesterone levels were measured in the HF herd. The JB herd, a ZEN-dominant model with low DON contamination, demonstrated ZEN levels that exceeded the Japanese limit in the purchased total mixed rations (TMR). Conversely, the HF herd, which primary consumes DON-dominant feed with low ZEN contamination, had high DON levels in the dent corn silage. Specifically, the JB herd's TMR contained 1.79 mg/kg ZEN and 0.58 mg/kg DON, whereas the HF herd's silage had 15.3 mg/kg DON (dried sample) and 0.1 mg/kg ZEN. Enzyme-linked immunoassay were used to measure urinary ZEN-DON levels following confirmation through liquid chromatography-tandem mass spectrometry. Urinary ZEN-DON levels measured were significantly correlated (p < 0.05, r > 0.6) in both herds. In the HF herd, AMH levels increased (p = 0.01) and serum amyloid A (SAA) levels decreased (p = 0.02) when contaminated and at the end of the monitoring period. Additionally, urinary ZEN and DON levels were significantly correlated with SAA levels (ZEN: p = 0.00, r = 0.46; DON: p = 0.03, r = 0.33), with an increase in ZEN and DON levels resulting in higher SAA levels. The JB herd showed no significant differences. Additionally, in the HF herd, 8-OHdG/Cre levels increased significantly during major contamination periods (p < 0.05). Clinical data from the HF herd indicated an increase in mastitis cases and treatment rates during periods of major contamination. Abortion rates in the HF herd decreased from 22.9% (before monitoring) to 8.9% (during the high contamination period) and finally to 1% (at the end of the monitoring period), with corresponding increases in progesterone levels. ZEN-DON contamination adversely affects breeding cattle's productivity, reproductive performance, and health. Therefore, monitoring urinary ZEN-DON is valuable for detecting contaminants and ensuring the safety of food products.

Synergistic Mitochondrial Genotoxicity of Carbon Dots and Arsenate in Earthworms Eisenia fetida across Generations: The Critical Role of Binding.

The escalating utilization of carbon dots (CDs) in agriculture raises ecological concerns. However, their combined toxicity with arsenic remains poorly understood. Herein, we investigated the combined mitochondrial genotoxicity of CDs and arsenate at environmentally relevant concentrations across successive earthworm generations. Iron-doped CDs (CDs-Fe) strongly bound to arsenate and arsenite, while nitrogen-doped CDs (CDs-N) exhibited weaker binding. Both CDs enhanced arsenate bioaccumulation without affecting its biotransformation, with most arsenate being reduced to arsenite. CDs-Fe generated significantly more reactive oxygen species than did CDs-N, causing stronger mitochondrial DNA (mtDNA) damage. Arsenate further exacerbated the oxidative mtDNA damage induced by CDs-N, as evidenced by increased reactive oxygen species, elevated 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG) levels, and a higher correlation between 8-OHdG and mtDNA damage. This was due to arsenic inhibiting the antioxidant enzyme catalase. This exacerbation was negligible with CDs-Fe because their strong binding with arsenic prevented catalase inhibition. Maternal mitochondrial DNA damage was inherited by filial earthworms, which experienced significant weight loss in coexposure groups coupled with mtDNA toxicity. This study reveals the synergistic genotoxicity of CDs and arsenate, suggesting that CDs could disrupt the arsenic biogeochemical cycle, increase arsenate risk to terrestrial animals, and influence ecosystem stability and health through multigenerational impacts.

Salivary 8-hydroxy-2′-deoxyguanosine levels in patients with oral cancer: a systematic review and meta-analysis

BackgroundDNA is an important target for oxidative attack and its modification may increase the risk of mutagenesis. The aim of this study was to evaluate and compare salivary levels of the oxidative stress biomarker 8-hydroxy-2′-deoxyguanosine (8-OHdG) in patients with oral cancer (OC) compared to the control group by a comprehensive search of the available literature.MethodsThe present systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered in Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/X3YMR. Four electronic databases were used to identify studies for this systematic review: PubMed, Scopus, ScienceDirect, and Web of Science from January 15, 2005, to April 15, 2021. The Joanna Briggs Institute (JBI) tool was used to assess article quality.ResultsOf the 166 articles identified, 130 articles were excluded on the basis of title and abstract screening (duplicates, reviews, etc.). Thirty-six articles were evaluated at full text and 7 articles met the inclusion criteria. Of these, only 5 studies had compatible data for quantitative analysis. An increase in salivary 8-OHdG levels was found in patients with OC compared to healthy subjects, but without statistical significance. 8-OHdG: SMD = 2,72 (95%CI= -0.25–5.70); *p = 0.07.ConclusionsThis systematic review and meta-analysis suggests a clear trend of increased 8-OHdG levels in saliva of OC patients compared to the control group. However, further studies are required to clarify and understand the altered levels of this oxidative stress marker.

Assessment of 8-Hydroxy-2’-Deoxyguanosine (8-OH-dG) Level in Urine as a Urinary Marker of Oxidative Stress in Children with Autism Spectrum Disorder

Abstract Background Autism spectrum disorder (ASD) is a developmental disorder characterized by deficits in social interaction, restricted interest and repetitive behavior. Oxidative stress in response to environmental exposure plays a role in virtually every human disease and represents a significant avenue of research into the etiology of ASD. Objective The aim of this study was to asses 8-hydroxy-2’-deoxyguanosine (8-OH-dG) level in urine as a urinary marker of oxidative stress in children with autism spectrum disorder in comparison to sex and age matched healthy control group. Patients and Methods We included 51 children with autism (43 males and 8 females whose age ranged from 2 to 16 years). They were compared to 51 children of the same age as a control group. The diagnosis of autism was made based on the criteria of autistic disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSMV). In the patients group, detailed medical history included sociodemographic form and family history was taken for autistic group also Intelligence Quotient test IQ test and Childhood Autism Rating Scale (CARS) used to measure the severity of autism. In the study, 8-OHdG values in urine were investigated using the enzyme-linked immunosorbent assay (ELISA) method and Urinary creatinine was determined with the Beckham Coulter analyzer and was used to normalize all biochemical measurements then the urinary 8-OHdG/creatinine levels were corrected to the urinary concentration of creatinine. Results The median age was 9.9 in the ASD group and 9.1 in the control group (P = 0.256). In the ASD group, (8-OH-dG)/creatinine ratio values were found to be significantly higher than those of the controls (P &amp;lt; 0.001). but also No statistically significant correlation between (8-OH- dG)/creatinie ratio and CARS score or IQ score (P = 0,7). Conclusion The data from this study supported the hypothesis of the oxidant/antioxidant balance as a key piece that may contribute to the autistic pathology

Magnolin alleviates cyclophosphamide-induced oxidative stress, inflammation, and apoptosis via Nrf2/HO-1 signaling pathway.

In the present study, we investigated the protective effect of magnolin (MAG) against oxidative stress induced by cyclophosphamide (CP) and its role in the Nrf2/HO-1 signaling pathway. Rats were administered MAG (1mg/kg, i.p.) for 14days and CP (75mg/kg, i.p.) on the 14th day. CP administration increased tissue damage, as evidenced by elevated levels of transaminases (aspartate and alanine), alkaline phosphatase, and renal parameters (blood urea nitrogen and creatinine). Additionally, 8-hydroxy-2'-deoxyguanosine and malondialdehyde levels were increased, whereas glutathione levels, along with catalase and superoxide dismutase activities, decreased in CP-treated rats. CP also down-regulated the expression of Bcl-2, HO-1, Nrf2, and NQO-1, while up-regulating Bax, Cas-3, TNF-α, Cox-2, iNOS, IL-6, IL-1β, and NFκB in liver and kidney tissues. In addition, CP treatment caused histopathological changes in heart, lung, liver, kidney, brain, and testis tissues. Treatment with MAG improved biochemical and oxidative stress parameters and prevented histopathological changes in CP-treated rats. Moreover, MAG suppressed the expression of inflammatory cytokines and apoptosis markers. In conclusion, MAG effectively prevented CP-induced toxicity by reducing oxidative stress, inflammation, and apoptosis, with its protective efficacy associated with the up-regulation of Nrf2/HO-1 signaling.

Histological and biochemical effects of an ethanolic extract of Myrtus communis leaf on the pancreases of rats fed high fat diets

ABSTRACT We investigated the effects of an ethanolic extract of Myrtus communis subsp. communis (MC) leaves on the pancreases of rats fed with a high fat diet (HFD). Wistar albino rats were fed either with standard lab chow (Control group) or with a 45% fat diet (HFD and HFD+MC groups) for 4 months, with the MC extract (100 mg/kg) being administered by orogastric gavage to rats in the HFD+MC group during the last month. Blood and pancreas samples were collected from all experimental groups at the end of the study. Insulin and leptin levels, and the lipid profile, were analyzed in the blood serum. Pancreatic injury was assessed histologically. Insulin, nuclear factor kappa beta (NF-κB), and alpha-smooth muscle actin (α-SMA) were assessed using immunohistochemistry. Apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) immunohistochemistry. In addition, oxidant/antioxidant activity was analyzed by biochemical methods. Increased body weight, serum insulin and leptin levels, blood glucose level and pancreatic tissue malondialdehyde (MDA), 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels, myeloperoxidase (MPO) activity and decreased tissue glutathione (GSH) level were observed in the HFD group compared to the Control group, in addition to dyslipidemia. An increased histopathological damage score, pancreatic islet area, insulin, TUNEL, NF-κB and α-SMA immunoreactivity were seen in animals from the HFD group compared to the Control group. However, such pathological changes were reduced in the HFD+MC group. Our data indicate further investigation of MC extract as a therapeutic adjuvant for HFD-induced pancreatic injury, acting via anti-inflammatory and antioxidant mechanisms, is worth carrying out.

Effects of Tanshinone IIA on Cognitive Impairment in Alzheimer’s Disease Rats Via Oxidative Stress, Inflammatory Responses and Apoptosis

Background The rationale for the pathogenesis of Alzheimer’s disease (AD) is the production of amyloid-beta (Aβ) and its resultant toxic effects. Purpose In this work, rats with AD were used as models to assess the modulatory effects of tanshinone IIA (tan IIA) in alleviating cognitive impairment, oxidative damage, inflammation and apoptosis. Materials and Methods Aβ1–42 was injected bilaterally in the hippocampus to establish an AD rat model. The effects of tan II A on the learning and memory capacities of AD rats were detected by ethological experiments. Tan IIA’s anti-inflammatory and antioxidant capacities were examined in this study using biochemical and immunohistochemical methods on rat hippocampus tissues. Results The experimental data showed that the cognitive ability of rats could be significantly improved by tan IIA. Furthermore, fewer injured neuron apoptosis was demonstrated in the tan IIA rats than in the AD group. More importantly, on the one hand, we discovered that the tan IIA group had considerably lower levels of interleukin 1 beta, tumour necrosis factor-alpha and inducible nitric oxide synthase. On the other hand, tan IIA was discovered to prevent oxidative stress by raising glutathione and superoxide dismutase activity and lowering malondialdehyde, protein carbonyl and 8-hydroxy-2′-deoxyguanosine levels. Conclusion Tan IIA can alleviate cognitive impairment and neuronal cell damage by inhibiting oxidative stress and inflammatory responses during AD.

Oxidative Stress Assessment in Colorectal Cancer Patients

Colorectal cancer (CRC), a global health challenge, exhibits rising incidence in low-income nations due to lifestyle changes. Oxidative stress, indicated by reactive oxygen species imbalance and Malondialdehyde (MDA), is linked to CRC. This study investigates oxidative stress markers, antioxidant enzymes, genetic markers, cellular regulation markers, and Vitamin E in CRC patients in Erbil. Ninety CRC patients and 30 healthy controls provided blood samples, processed and stored at –20°C. Enzyme-linked immunosorbent assay kits quantified oxidative stress, antioxidant markers, and Vitamin E. Oxidative stress markers showed significant differences, with elevated MDA and 8-hydroxy-2’-deoxyguanosine levels in patients. Nitrotyrosine exhibited lower expression in patients. Antioxidant enzymes glutathione peroxidase and superoxide dismutase were enhanced in patients, while glutathione (GSH), glutathione reductase and catalase levels were significantly lower in patients. The genetic marker KRAS showed a substantial decrease in patients (&lt;0.0001) but both adenomatous polyposis coli (APC) and CRC antigen (CCA) were higher. Serum vitamin E levels were significantly lower in patients (71.78 ± 6.368) compared to controls (142.3 ± 4.828, p &lt; 0.0001). Elevated oxidative stress, altered enzymatic activity, significantly lower expression of KRAS, and higher expression of APC and CCA in the patient group. Furthermore, reduced Vitamin E levels were observed in the patient group, highlighting potential challenges in antioxidant defense.

H2O2-Induced Oxidative Stress Responses in Eriocheir sinensis: Antioxidant Defense and Immune Gene Expression Dynamics.

Eriocheir sinensis, a key species in China's freshwater aquaculture, is threatened by various diseases, which were verified to be closely associated with oxidative stress. This study aimed to investigate the response of E. sinensis to hydrogen peroxide (H2O2)-induced oxidative stress to understand the biological processes behind these diseases. Crabs were exposed to different concentrations of H2O2 and their antioxidant enzyme activities and gene expressions for defense and immunity were measured. Results showed that activities of antioxidant enzymes-specificallysuperoxide dismutase (SOD), catalase (CAT), total antioxidant capacity(T-AOC), glutathione (GSH), and glutathione peroxidase (GSH-Px)-varied with exposure concentration and duration, initially increasing then decreasing. Notably, SOD, GSH-Px, and T-AOC activities dropped below control levels at 96 h. Concurrently, oxidative damage markers, including malondialdehyde (MDA), H2O2, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, increased with exposure duration. The mRNA expression of SOD, CAT, and GSH-Px also showed an initial increase followed by a decrease, peaking at 72 h. The upregulation of phenoloxidaseloxidase (proPO) and peroxinectin (PX) was also detected, but proPO was suppressed under high levels of H2O2. Heat shock protein 70 (HSP70) expression gradually increased with higher H2O2 concentrations, whereas induced nitrogen monoxide synthase (iNOS) was upregulated but decreased at 96 h. These findings emphasize H2O2's significant impact on the crab's oxidative and immune responses, highlighting the importance of understanding cellular stress responses for disease prevention and therapy development.

Effect of hyperbaric oxygen treatment on ischaemia-reperfusion injury in rats detorsioned after experimental ovarian torsion.

This study aimed to investigate whether hyperbaric oxygen treatment (HBOT) could ameliorate ischaemia-reperfusion injury in a rat model of ovarian torsion-detorsion. Twenty-seven rats were divided among four groups: surgical sham rats (S) (n = 6) underwent identical anaesthesia and surgical incisions to other groups (n = 7 per group) but with no ovary intervention; torsion rats (T) underwent laparotomy, ovarian torsion, relaparotomy and sacrifice after three hours; torsion and detorsion rats (T/DT) underwent laparotomy, ovarian torsion (three hours), relaparotomy and detorsion, and sacrifice after one week; torsion, detorsion, hyperbaric oxygen rats (T/DT/HBOT) underwent laparotomy, ovarian torsion, relaparotomy and detorsion, and sacrifice after one week during which HBOT was provided 21 times (100% oxygen at 600 kPa for 50 min). In all groups blood collection for markers of oxidative stress or related responses, and ovary collection for histology were performed after sacrifice. When the T/DT, and T/DT/HBOT groups were compared, 8-hydroxy-2'-deoxyguanosine (a marker of oxidative damage to DNA) and malondialdehyde (a product of lipid peroxidation) levels were lower in the T/DT/HBOT group. Anti-Mullerian hormone levels were higher in the T/DT/HBOT group compared to the T/DT group. In addition, oedema, vascular occlusion, neutrophilic infiltration and follicular cell damage were less in the T/DT/HBOT group than in the T/DT group. When biochemical and histopathological findings were evaluated together, HBOT appeared reduce ovarian ischaemia / reperfusion injury in this rat model of ovarian torsion-detorsion.

Ataxia telangiectasia and Rad3-related (ATR) inhibition by VE-822 potently reversed 5-flourouracil resistance in colorectal cancer cells through targeting DNA damage response.

VE-822 is a novel inhibitor of ATR, a key kinase involved in the DNA damage response pathway. The role of ATR inhibition in reversing drug resistance in various cancer types has been investigated. Therefore, this study investigated the effects of ATR inhibition by VE-822 on reversing 5-fluorouracil (5-FU) resistance in colorectal cancer cell line (Caco-2). Caco-2 and 5-FU resistance Caco-2 (Caco-2/5-FU) cells were treated with 5-FU and VE-822, alone and in combination. Cell proliferation and viability were assessed by MTT assay and Trypan Blue staining. P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) activities were measured by Rhodamine123 accumulation and uptake assay. The mRNA levels of P-gp, MRP-1, ataxia telangiectasia and Rad3-related (ATR) and checkpoint kinase 1 (CHK1) were measured by qRT-PCR. Western blot was used to measure the protein levels of P-gp, MRP-1, γ-H2AX, ATR and CHK1 in cells. 8-Oxo-2'-deoxyguanosine (8-oxo-dG) levels were determined via ELISA. Apoptosis was evaluated by ELISA death assay, DAPI staining and lactate dehydrogenase (LDH) assay. The Caco-2/5-FU cells showed lower levels of 5-FU mediated proliferation inhibition in comparison to Caco-2 cells. VE-822 decreased the IC50 value of 5-FU on resistant cells. In addition, the expression levels and activity of P-gp and MRP-1 were significantly decreased in resistant cells treated with VE-822 (P < 0.05). The combination of 5-FU and VE-822 increased apoptosis in Caco-2/5-FU cells by downregulating CHK1 and ATR and upregulating γ-H2AX and 8-oxo-dG. The simultaneous treatment of resistant colorectal cancer cells with 5-FU and ATR inhibitor, VE-822, was demonstrated to be effective in reversing drug resistance and potentiating 5-FU mediated anticancer effects via targeting DNA damage.

Correlation Between the 8-hydroxy-2'-deoxyguanosine Levelin the Peritoneal Solution of Patients Undergoing PeritonealDialysis and the Peritoneal Equilibration Test, Kt/V, Ferritin,and Albumin Levels.

Peritoneal dialysis (PD) is an effective treatment modality for advanced kidney failure, offering patients a significant degree of independence. However, the long-term use of PD is limited due to the degeneration of the peritoneal membrane, resulting in reduced dialysis adequacy. Evaluating the peritoneal membrane condition in patients with advanced kidney failure who are undergoing PD is challenging with existing methods. Therefore, this study aimed to investigate the correlation between 8-hydroxy-2'-deoxyguanosine (8OHDG) levels in the peritoneal solution of patients undergoing PD and various factors, such as peritoneal equilibration test (PET), dialysis adequacy (Kt/V), underlying diseases, serum ferritin, and albumin levels. 8OHDG is a sensitive marker of oxidative stress caused by DNA damage. A total of 56 patients were included in this cross-sectional study. Five milliliters of PD fluid were collected from the patients, and 8-OHdG levels were measured using ELISA method. Then, they were compared with PET, Kt/V, albumin, and ferritin markers in the patients' files, and the results were analyzed by statistical tests. The study examined the correlation between 8OHDG and other markers. It was found that this index had significant associations with PET and underlying HTN (P < .05), whereas no significant associations were identified with the other markers. The results of the present study demonstrate that the level of 8OHDG, as one of the oxidative stress markers, could be used to evaluate the function of the peritoneum in patients undergoing PD. DOI: 10.52547/ijkd.7654.

Excavatolide C/cisplatin combination induces antiproliferation and drives apoptosis and DNA damage in bladder cancer cells.

Excavatolide C (EXCC), a marine coral-derived compound, exhibits an antiproliferation effect on bladder cancer cells. The present study evaluated the improvement in the antiproliferation ability of EXCC by co-treatment with cisplatin in bladder cancer cells. EXCC/cisplatin (12.5 and 1μg/mL) showed higher antiproliferation effects on bladder cancer cells than single treatments (EXCC or cisplatin alone) in the 48h ATP assay. EXCC/cisplatin also enhanced the increase in subG1, annexin V-mediated apoptosis, and activation of poly (ADP-ribose) polymerase (PARP) and several caspases (caspases 3, 8, and 9) compared to the single treatments. Cellular and mitochondrial oxidative stress was enhanced with EXCC/cisplatin compared to the single treatments according to analyses of reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial membrane potential; in addition, cellular antioxidants, such as glutathione (GSH), and the mRNA expressions of antioxidant signaling genes (catalase and NFE2-like bZIP transcription factor 2) were downregulated. EXCC/cisplatin treatment produced more DNA damage than the single treatments, as indicated by γH2AX and 8-hydroxy-2'-deoxyguanosine levels. Moreover, several DNA repair genes for homologous recombination (HR) and non-homologous end joining (NHEJ) were downregulated in EXCC/cisplatin compared to others. The addition of the GSH precursor N-acetylcysteine, which has ROS scavenging activity, attenuated all EXCC/cisplatin-induced changes. Notably, EXCC/cisplatin showed lower antiproliferation, apoptosis, ROS induction, GSH depletion, and γH2AX DNA damage in normal cells than in bladder cancer cells. Therefore, the co-treatment of EXCC/cisplatin reduces the proliferation of bladder cancer cells via oxidative stress-mediated mechanisms with normal cell safety.

NMR Untargeted and HPLC-MS/MS Targeted Metabolomic Approaches for Evaluating Styrene Exposure in the Urine of Shipyard Workers.

Due to its chemical properties, styrene is largely employed in the manufacturing of several products including rubber, polymers and resins, and it is particularly suitable for shipbuilding industry purposes. In this context, the main exposure to styrene occurs in occupational settings. Despite its widespread use, its long-term effects on human health at the occupational level are still unclear. The aim of this pilot study was to evaluate changes in styrene exposure biomarkers related to the metabolic and oxidative stress profiles in the urine of seventeen shipyard workers and seventeen non-exposed subjects. Urinary metabolites were assessed by means of NMR spectroscopy, including mandelic and phenylglyoxylic acids; four oxidative stress biomarkers, namely 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydroguanosine, and 8-oxo-7,8-dihydro-2'-deoxyguanosine and 3-nitrotyrosine, were evaluated via HPLC-MS/MS. The metabolic profiles of exposed workers showed both long- and short-term metabolic responses to styrene exposure compared to non-exposed subjects. From the comparison between non-exposed and before-shift workers, only 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine levels were significantly different (long term exposure response). At the same time, comparing the non-exposed group with after-shift workers, we observed lower levels of pseudouridine and 1-methylnicotinamide and higher glutamine levels in after-shift workers. The comparison between before-shift and after-shift workers showed that 8-oxo-7,8-dihydroguanine significantly increased after the shift, suggesting its involvement in the exposure to styrene (short-term exposure response). The obtained results, although preliminary, allow us to lay the basis for further human studies aimed at establishing a global understanding of styrene metabolism.

GLI family zinc finger protein 2 promotes skin fibroblast proliferation and DNA damage repair by targeting the miR-200/ataxia telangiectasia mutated axis in diabetic wound healing.

Diabetic foot ulcer (DFU) is a serious complication of diabetic patients which negatively affects their foot health. This study aimed to estimate the role and mechanism of the miR-200 family in DNA damage of diabetic wound healing. Human foreskin fibroblasts (HFF-1 cells) were stimulated with high glucose (HG). Db/db mice were utilized to conduct the DFU in vivo model. Cell viability was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. Superoxide dismutase activity was determined using detection kits. Reactive oxygen species determination was conducted via dichlorodihydrofluorescein-diacetate assays. Enzyme-linked immunosorbent assay was used to evaluate 8-oxo-7,8-dihydro-2'deoxyguanosine levels. Genes and protein expression were analyzed by quantitative real-time polymerase chain reaction, western blotting, or immunohistochemical analyses. Luciferase reporter gene and RNA immunoprecipitation assays determined the interaction with miR-200a/b/c-3p and GLI family zinc finger protein 2 (GLI2) or ataxia telangiectasia mutated (ATM) kinase. HG repressed cell proliferation and DNA damage repair, promoted miR-200a/b/c-3p expression, and suppressed ATM and GLI2. MiR-200a/b/c-3p inhibition ameliorated HG-induced cell proliferation and DNA damage repair repression. MiR-200a/b/c-3p targeted ATM. Then, the silenced ATM reversed the miR-200a/b/c-3p inhibition-mediated alleviative effects under HG. Next, GLI2 overexpression alleviated the HG-induced cell proliferation and DNA damage repair inhibition via miR-200a/b/c-3p. MiR-200a/b/c-3p inhibition significantly promoted DNA damage repair and wound healing in DFU mice. GLI2 promoted cell proliferation and DNA damage repair by regulating the miR-200/ATM axis to enhance diabetic wound healing in DFU.

Temperature stability of urinary F2-isoprostane and 8-hydroxy-2′-deoxyguanosine

BackgroundClinical and epidemiological studies employ long-term temperature storage but the effect of temperature on the stability of oxidative stress (OS) markers is unknown. We investigated the effects of storage at −20 °C and −80 °C over 4–9 months on F2-isoprostanes (F2-IsoP) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in urine of children, a population group among whom the measurement of these markers is still limited. MethodsPaired spot urine samples from 87 children aged 8.9–16.9 years (52.9% boys) were analyzed. Samples were preserved with 0.005% (w/v) butylated hydroxytoluene, portioned and stored within 2.5 h (median) of collection. Samples were analyzed in duplicate or triplicate using commercial ELISA kits and their correlations were evaluated. ResultsF2-IsoP and 8-OHdG showed high correlations (Spearman rho of 0.90 and 0.97, respectively; P < 0.0001) with storage at −20 °C and −80 °C. There was a strong agreement among categories of values for F2-IsoP (Kappa = 0.76 ± 0.08, agreement = 83.9%, P < 0.0001) and 8-OHdG: (Kappa = 0.83 ± 0.08, agreement = 88.4%, P < 0.0001). The correlation between the temperatures for F2-IsoP concentrations was also high when stored for <4 (0.93), 4 (0.93), and 5 months (0.88), all P < 0.0001. For 8-OHdG, Spearman correlations at <8, 8, and 9 months of storage at −20 °C and −80 °C were 0.95, 0.98, and 0.96 (all P < 0.0001), respectively. ConclusionsUrine storage with BHT for up to nine months at a temperature of −20 °C to −80 °C yields highly comparable concentrations of F2-IsoP and 8-OHdG.

A lupin protein hydrolysate protects the central nervous system from oxidative stress in WD-fed ApoE-/- mice.

Oxidative stress plays a crucial role in neurodegenerative diseases like Parkinson's and Alzheimer's. Studies indicate the relationship between oxidative stress and the brain damage caused by a high-fat diet. It is previously found that a lupin protein hydrolysate (LPH) has antioxidant effects on human leukocytes, as well as on the plasma and liver of Western diet (WD)-fed ApoE-/- mice. Additionally, LPH shows anxiolytic effects in these mice. Given the connection between oxidative stress and anxiety, this study aimed to investigate the antioxidant effects of LPH on the brain of WD-fed ApoE-/- mice. LPH (100 mg kg-1) or a vehicle is administered daily for 12 weeks. Peptide analysis of LPH identified 101 amino acid sequences (36.33%) with antioxidant motifs. Treatment with LPH palliated the decrease in total antioxidant activity caused by WD ingestion and regulated the nitric oxide synthesis pathway in the brain of the animals. Furthermore, LPH increased cerebral glutathione levels and the activity of catalase and glutathione reductase antioxidant enzymes and reduced the 8-hydroxy-2'-deoxyguanosine levels, a DNA damage marker. These findings, for the first time, highlight the antioxidant activity of LPH in the brain. This hydrolysate could potentially be used in future nutraceutical therapies for neurodegenerative diseases.