Total Oxidative Stress Research Articles

CGAS regulates metabolic reprogramming independently of STING pathway in colorectal cancer

BackgroundCyclic GMP-AMP synthase (cGAS) is widely acknowledged for detecting cytosolic chromatin fragments and triggering innate immune responses through the production of the second messenger cGAMP, which subsequently activates the adaptor protein STING. However, the role of cGAS in regulating metabolic reprogramming independently of STING activation has not yet been explored. MethodsGene set enrichment pathway analysis (GSEA) based on TCGA transcriptomics, combined with Seahorse metabolic analysis of CRC cell lines and human normal colonic mucosa cell line FHC, was performed to profile the metabolic features in CRC. cGAS doxycycline- (dox) inducible knockout (iKO) CRC sublines were generated to investigate the role of cGAS in CRC. Transcriptome and proteome data from COAD cohorts were utilized to evaluate the RNA and protein expression levels of cGAS in COAD tissues and normal colon tissues. Overall survival information of patients with COAD was used to evaluate the prognostic value of cGAS expression. Colony formation assays were conducted to evaluate the clonogenicity of CRC cells under different situations. Flow cytometry detecting the signal of fluorogenic reactive oxygen species (ROS) probes was performed to evaluate the total cellular and mitochondrial oxidative stress level in CRC cells. A propidium iodide (PI) staining assay was used to evaluate the cell death level in CRC cells. Quantitative PCR (qPCR) was conducted to detect the RNA level of STING pathway downstream target genes. Mass spectrometry was used for the identification of novel binding partners of cGAS in CRC cells. Co-immunoprecipitation (co-IP) was conducted to confirm the interaction between cGAS and NDUFA4L2. ResultsBy integrating metabolic pathway analysis based on TCGA transcriptomics with Seahorse metabolic analysis of a panel CRC cell lines and the human normal colonic mucosa cell line FHC, we demonstrated that CRC cells exhibit typical characteristics of metabolic reprogramming, characterized by a shift from oxidative phosphorylation (OXPHOS) to glycolysis. We found that cGAS is critical for CRC cells to maintain this metabolic switch. Specifically, the suppression of cGAS through siRNA-mediated knockdown or doxycycline-inducible knockout reversed this metabolic switch, resulting in increased OXPHOS activity, elevated production of OXPHOS byproduct reactive oxygen species (ROS), and consequently caused oxidative stress. This disruption induced oxidative stress, ultimately resulting in cell death and reduced cell viability. Moreover, significant upregulation of cGAS in CRC tissues and cell lines and its association with poor prognosis in CRC patients was observed. Subsequently, we demonstrated that the role of cGAS in regulating metabolic reprogramming does not rely on the canonical cGAS-STING pathway. Co-immunoprecipitation combined with mass spectrometry identified NDUFA4L2 as a novel interactor of cGAS. Subsequent functional experiments, including mitochondrial respiration and oxidative stress assays, demonstrated that cGAS plays a crucial role in sustaining elevated levels of NDUFA4L2 protein expression. The increased expression of NDUFA4L2 is essential for cGAS-mediated regulation of metabolic reprogramming and cell survival in CRC cells. ConclusioncGAS regulates metabolic reprogramming and promotes cell survival in CRC cells through its interaction with NDUFA4L2, independently of the canonical cGAS-STING pathway.

Effects of Oregano Aromatic Water (Oreganum onites L.) Supplementation on Diets of Lactating Dairy cows on Milk Production Performance, Metabolic Health and Antioxidative Defense Mechanism

This study aimed to validate the effect of oregano aromatic water (OAW) on blood parameters, oxidative stress, and production and composition of milk when used as a feed additive. Thirty lactating Holstein cows (average 570 kg), average 74 days in milk and 2.44 lactation number, were randomly divided into three groups for a period of 60-days. These groups included: (G1) control ration, (G2) control ration + OAW (10 mg/kg of DM), (G3) control ration + OAW (20 mg/kg of DM). Milk production (MP) were unaffected by OAW doses (P>0.05). The supplementation of OAW did not affect the milk composition, and somatic cell count (SCC) (P>0.05). OAW supplementation did not affect blood biochemical values except ketone and glucose. The glucose value increased as the ketone decreased with OAW supplementation (P<0.05). The hematological blood values were not found to be significant. OAW significantly decreased Total oxidant capacity (TOC) and oxidative stress index (OSI) while increasing Total antioxidant capacity (TAC). The current study's findings indicated that OAW can be used as a feed additive to improve cow health and milk production.

Nigella sativa oil attenuates inflammation and oxidative stress in experimental myocardial infarction.

A growing interest in using Nigella sativa oil (NSO) in the prevention or treatment of several cardiovascular diseases has prompted this study. The research aims to investigate the effect of NSO on cardiac damage prevention after long-term administration in induced myocardial infarction (MI) in rats. NSO was analyzed for its fatty acids composition using gas chromatography-mass spectrometry (GC-MS) analysis and administered in rats before and after isoproterenol (45mg/kg body weight) induced myocardial infarction. The following parameters were assessed: electrocardiograms, histopathological examination, serum biochemical aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase-myocardial band (CK-MB), serum and heart inflammation (tumor necrosis factor-alpha (TNF), interleukin 1 beta (IL-1b), and interleukin 6 (IL-6)), and tissue oxidative stress (total antioxidant capacity (TAC), total oxidative stress (TOS), nitric oxide (NO), malondialdehyde (MDA), and the total thiols (THIOL)). Linoleic acid (C18:2n-6) and oleic acid (C18:1n-9) were approximately 89% of total fatty acids while palmitic acid (C16:0) was 6.10%. Administration of NSO for 28 days helped in preventing QT and QTc interval prolongation and reduced heart rate (HR), after MI induction. The histological assessment showed improvement in myofibrillary degeneration and necrosis and also better reduced inflammatory process in the groups treated with NSO. In serum, pro-inflammatory cytokines IL-1b and IL-6 were downregulated in chronic conditions (for IL-1b, NSO vs. control was 86.09vs 150.39 pg/mL, and for IL-6 NSO vs. control was 78.00 vs. 184.98 pg/ml). In the heart tissue, the downregulation was observed only for TNF in both acute and chronic conditions (acute NSO vs. control was 132.37 vs. 207.63 pg/mL, and chronic NSO vs. control was 135.83 vs. 183.29 pg/ml). The pro-oxidant parameters TOS, NO, MDA, and OSI, were reduced in the groups treated with NSO only after 14 days of treatment, suggesting that the NSO antioxidant effect is time-dependent. NSO administration might have a favourable impact on the regulation of oxidative stress and inflammation processes after MI induction in rats, and it is worth considering its administration as an adjuvant treatment.

Effects of Apelin-13 on auditory system in STZ-induced diabetic rats

AimDamage to the auditory pathways is one of the complications of diabetes. The aim of this study was to investigate the potential therapeutic effects of apelin-13 in the auditory pathways of rats with experimentally induced diabetes by examining its effect on auditory brainstem responses, cochlear oxidative stress and inflammatory cytokines. MethodsThirty-two male Wistar albino rats were divided into four groups: sham control, diabetes, apelin and diabetes + apelin. A single dose of 45 mg/kg streptozotocin (STZ) was administered to induce diabetes. The apelin group received 50 µg/kg apelin-13 for seven days intraperitoneally (ip). At the end of the apelin and STZ applications auditory brainstem responses (ABR) was recorded. At the end of the experiment, cochlea was removed and biochemical analyzes were performed. ResultsIn ABR recordings, the latencies of wave V in diabetic group were observed to be longer than those of the control, with the apelin treatment exhibiting a partial reversal of this situation, particularly at specific frequencies and intensity levels. Apelin treatment leads to a significant increase in total antioxidant status (TAS) and a reduction in total oxidant status (TOS) and oxidative stress index (OSI) in cochlea compared to diabetic groups. The levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1 beta) in cochlear tissue were found to be significantly reduced in the apelin-treated group compared to the diabetic group. ConclusionApelin-13 may have a protective effect on the auditory system and may be proposed as a potential new therapeutic strategy for the management diabetic auditory impairment.

Synergistic therapeutic effect of Guggul gum resin on antidiabetic activity of saxagliptin

Type 2 Diabetes Mellitus is an endocrine metabolic disorder leading to impaired glucose utilization. This disease is managed by both commercial drugs and herbal products eliciting various interactions. The evaluation of one such interaction between saxagliptin (SAXA, substrate of CYP3A4), and Guggul extract (GE) from Commiphora wightii is done in this present study. The concomitant administration of the SAXA with GE had restored the levels of otherwise increased blood glucose and biochemical parameters and otherwise decreased total glycogen and oxidative stress markers more effectively as compared to the solely consumed SAXA or GE. These results were corroborated by histopathological evaluation where the combination treatment showed better mitigation of hepatic, renal and pancreatic tissue damage that occurred due to induced diabetes. Furthermore, CYP3A11 mRNA (murine homolog to human CYP3A4) expression levels were observed to be reduced to non-diabetic levels in combination therapy which was otherwise unachievable. The molecular docking studies predicted improved interaction between CYP3A4 and bioactive content of GE, i.e., guggulsterone E-Z, possessing binding energy of -9.96 kcal/mol along with SAXA, confirming the co-existence of both the ligands at different binding sites of the metabolizing enzyme. The synergistic interactions of GE and SAXA helped in better restoration of tissue damage and increased CYP3A11 mRNA expression levels caused by induced diabetes.

Mistletoe (Loranthus europaeus Jacq.): antioxidant, antimicrobial and anticholinesterase activities

Plants are natural resources responsible for different biological activities. Determining the biological activities of plants is very important. In our study, some biological activities and total phenolic and flavonoid contents of Loranthus europaeus Jacq. were determined. In this context, ethanol and methanol extracts of the plant were obtained using the soxhlet device. Total antioxidant, total oxidant, and oxidative stress statuses were determined using Rel Assay kits. Antimicrobial activity was tested against standard bacterial and fungal strains using the agar dilution test. Anticholinesterase activity was determined by detecting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities. Determination of total phenolic content was determined using the Folin-Ciocalteu reagent. Total flavonoid quantification was performed using an aluminum chloride assay. As a result of the study, TAS values (Total antioxidant status) of ethanol and methanol extracts of the plant were determined as 5.620±0.134 and 6.384±0.134 mmol/L, respectively. TOS values (Total oxidant status) were determined as 10.997±0.183 and 13.368±0.222 µmol/L, respectively. OSI values (Oxidative stress index) were measured as 0.196±0.004 and 0.209±0.003, respectively. TPC (Total phenolic content) value was determined as 34.49±1.78 and 55.82±2.34 mg/g, respectively, and TFC (Total flavonoid content) value was determined as 46.10±2.40 and 55.49±1.15 mg/g, respectively. Ethanol and methanol extracts of the plant were found to be effective against bacterial and fungal strains at concentrations between 50-200 µg/mL. In addition, the anti-AChE values of ethanol and methanol extracts were determined as 13.51±0.81 and 22.79±1.86 µg/mL, respectively, and the anti-BChE values were determined as 27.84±0.62 and 33.08±1.63 µg/mL, respectively. According to the results obtained, it was determined that L. europaeus has antioxidant, antimicrobial, and anticholinesterase activity. In this context, it is thought that it can be used as a natural material in pharmacological designs.

The Dynamics of Allelochemicals and Phytotoxicity in Eisenia fetida during the Decomposition of Eucalyptus grandis Litter.

Allelopathy is an underlying and controversial mechanism for detrimental environmental effects in the management of Eucalyptus plantations. However, little attention has been paid to the dynamics of allelochemicals and phytotoxicity in soil fauna during litter decomposition. To explore the relationship between the dynamics of phytotoxicity and allelochemicals, a decomposition experiment was conducted using 4-year-old and 8-year-old Eucalyptus grandis litter (0, 10, 20, 30, and 45 days). The acute toxicity of Eisenia fetida was assessed, and a chemical analysis of the eucalyptus leaves was performed. Biochemical markers, including total protein, acetylcholinesterase (AChE) activity, and oxidative stress levels (SOD and MDA) were measured. A comet assay was used to determine DNA damage in E. fetida cells. The results showed that after 20-30 days of decomposition, E. grandis litter exhibited stronger phytotoxic effects on E. fetida in terms of growth and biochemical levels. After 20 days of decomposition, the weight and total protein content of E. fetida first decreased and then increased over time. SOD activity increased after 20 days but decreased after 30 days of decomposition before increasing again. MDA content increased after 20 days, then decreased or was stable. AChE activity was inhibited after 30 days of decomposition and then increased or stabilized with further decomposition. Soluble allelochemicals, such as betaine, chlorogenic acid, and isoquercitrin, significantly decreased or disappeared during the initial decomposition stage, but pipecolic acid significantly increased, along with newly emerging phenolic fractions that were present. More allelochemicals were released from 8-year-old litter than from 4-year-old E. grandis litter, resulting in consistently more severe phytotoxic responses and DNA damage in E. fetida. Scientific management measures, such as the appropriate removal of leaf litter in the early stages of decomposition, might help support greater biodiversity in E. grandis plantations.

Effects of 8-week strength training on basal hormone levels, sex hormone binding globulin, insulin-like growth factor binding protein-3, oxidative stress markers, and IL-6 levels in adolescent athletes.

The aim of the study was to investigate how 8-week strength training affects adolescent athletes' basal hormone concentrations, sex hormone binding globulin (SHBG), insulin-like growth factor binding protein-3 (IGFBP-3), cytokine, and oxidative stress markers. Twenty adolescent handball players participated in this study. The participants were randomly divided into the strength training group (ST, n = 10) and the control group (C, n = 10). ST participates in strength training 3 sessions a week for 8 weeks and C participates only in handball training. We quantified serum basal hormone concentration, SHBG, IGFBP3, oxidative stress markers, and IL-6 in each subject's blood samples before and after 8 weeks of strength training. Interestingly, while insulin-like growth factor-1 (IGF-1) concentration declined in group C (p < 0.05), it did not in ST (p > 0.05). Furthermore, the basal concentration of growth hormone (GH), total testosterone (T), cortisol (Cor), total antioxidant status (TAS), and serum-free androgen index (FAI) basal concentration did not change in ST and C. Basal IGFBP-3 and SHBG concentrations decreased only in ST (p < 0.05), but not in C (p > 0.05). Serum-free testosterone (FT) levels increased in ST and C (p > 0.05). Total oxidant status (TOS) and oxidative stress index (OSI) reduced ST and C (p < 0.05). Serum interleukin-6 (IL-6) levels did not alter groups ST and C. Strength training did not affect basal serum concentrations of T, GH, IGF-1, COR, IL-6, and TAS, but it caused a decrease in SHBG and IGFBP3 concentrations in ST. Increased basal FT concentration and improved serum TOS may not depend on strength training.

Determining the effects of erythrocyte suspension on total antioxidant status and total oxidative stress values in pediatric intensive care patients

Determining the effects of erythrocyte suspension on total antioxidant status and total oxidative stress values in pediatric intensive care patients

The effect of astaxanthin after varicocele surgery on antioxidant status and semen quality in infertile men: A triple-blind randomized clinical trial.

Varicocele (VC) is widely recognized as a prevalent etiological factor contributing to male infertility. It has been established that the generation of reactive oxygen species (ROS) plays a significant role in the progression and development of VC. Antioxidants may regulate ROS levels in these patients. Astaxanthin (ASX) is a carotenoid compound with notable antioxidant and anti-inflammatory characteristics. The current study postulated that the administration of ASX following varicocelectomy (VCT) could potentially enhance antioxidant status and semen quality in these patients. A total of 40 infertile males with clinical VC and abnormal semen analyses were randomly assigned to take part in the current trial. For 3 months following surgery, the intervention group took ASX (6 mg/day) while the control group received a placebo. After intervention, semen parameters, antioxidant status, and pro-inflammatory cytokines were compared between the two groups. Regarding semen parameters, antioxidant treatment led to a significant improvement in total and progressive motility in the treatment group (p < 0.05). Additionally, ASX led to a considerable increase in the expression levels of NRF2, Keap1, SOD2, SOD3, and BCL2, though the enhancement in the expression level of SOD3 was not statistically significant (p > .05). However, ASX significantly decreased the BAX expression level (p < .05). Even though the level of total antioxidant capacity (TAC) of seminal fluid (SF) increased significantly in the treatment group (p < .05), the level of total oxidative stress (TOS) in SF did not differ substantially between treatment and control groups (p > .05). Based on inflammatory factors in SF, ASX led to a considerable reduction in levels of TNF-α, IL-1β, and IL-6 (p < .05). Our findings demonstrated that ASX treatment provides an important contribution to VCT outcomes by modulating antioxidant status and pro-inflammatory cytokines. Our results indicated that ASX may be beneficial as an adjuvant therapy for infertile men following VCT.

Elucidating the effect of levothyroxine and triiodothyronine on methylglyoxal derived stress.

Methylglyoxal (MG) is the most potent precursor during the formation of the advanced glycation end products (AGEs). MG-dependent glycative stress contributes to pathogenesis of diabetes, age-related disorders, and cancer. There is a great need to study the reduction process of glycative stress for effective management of metabolic disorders. From natural compounds to synthetic drugs, each element contributes to the reduction of glycative stress. Previously, it was established that the lowering of uric acid, low-density lipoprotein cholesterol, and urine albumin excretion rate, as well as reducing total oxidative stress, were all achieved more effectively with a levothyroxine regimen. Still, there is no such study found that supports the MG-dependent glycative stress reduction with thyroid hormone compound. Our study aims to investigate the effects of T3 and T4 on MG-dependent glycative stress. The antiglycation effect was assayed through NBT assay, DNPH assay, ELISA, and fluorescence spectrophotometer. The intracellular reduction in reactive oxygen species (ROS) has been estimated through confocal microscopy. The results revealed an effective reduction in the formation of AGEs adducts and intracellular ROS formation. The investigation concludes AGEs formation was suppressed using these compounds, although in vivo and rigorous clinical trials are required in order to verify these findings.

Total Antioxidant Status and Oxidative Stress in Patients with COVID-19 Infection.

Oxidative stress (OS) may have a role in the pathogenesis and severity of the coronavirus disease 2019 (COVID-19) disease. The present study was conducted to estimate the association of inflammatory markers, total antioxidant status (TAS), and malondialdehyde (MDA) levels with the severity of the disease and to identify their trends after recovery. Adult patients admitted with moderate or severe COVID-19 were included after obtaining written informed consent from patient or next of kin. Patients who were critically ill, on ventilator, or in sepsis/septic shock were excluded. Levels of inflammatory markers, TAS, and OS as measured by MDA were estimated within 24 hours of admission and reevaluated at 12 weeks following discharge. The mean age of the 40 patients (42.5% females) was 55 ± 15 years. TAS values (in trolox equivalents/L) were significantly reduced in severe compared to moderate COVID-19 patients at admission (7.2 ± 4.19 vs 12.3 ± 5.21). These increased at 12 weeks after discharge. The MDA levels (in nmol/mL) were significantly higher in severe in comparison to moderate disease (7.1 ± 2.68 vs 4.1 ± 1.81). These values showed a downward trend 12 weeks after discharge in severe disease group. Admission levels of interleukin-6 (IL-6), D-dimer, and lactate dehydrogenase (LDH) were statistically higher in severe COVID-19 patients in contrast to moderate disease. Moderate and severe COVID-19 are associated with a state of high OS and a low total antioxidant levels which tend to recover at 3 months following discharge.

Effects of Sevoflurane and Fullerenol C60 on the Heart and Lung in Lower-Extremity Ischemia-Reperfusion Injury in Streptozotocin-Induced Diabetes Mice.

Background and Objectives: Lower-extremity ischemia-reperfusion injury can induce distant organ ischemia, and patients with diabetes are particularly susceptible to ischemia-reperfusion injury. Sevoflurane, a widely used halogenated inhalation anesthetic, and fullerenol C60, a potent antioxidant, were investigated for their effects on heart and lung tissues in lower-extremity ischemia-reperfusion injury in streptozotocin (STZ)-induced diabetic mice. Materials and Methods: A total of 41 mice were divided into six groups: control (n = 6), diabetes-control (n = 7), diabetes-ischemia (n = 7), diabetes-ischemia-fullerenol C60 (n = 7), diabetes-ischemia-sevoflurane (n = 7), and diabetes-ischemia-fullerenol C60-sevoflurane (n = 7). Diabetes was induced in mice using a single intraperitoneal dose of 55 mg/kg STZ in all groups except for the control group. Mice in the control and diabetes-control groups underwent midline laparotomy and were sacrificed after 120 min. The DIR group underwent 120 min of lower-extremity ischemia followed by 120 min of reperfusion. In the DIR-F group, mice received 100 μg/kg fullerenol C60 intraperitoneally 30 min before IR. In the DIR-S group, sevoflurane and oxygen were administered during the IR procedure. In the DIR-FS group, fullerenol C60 and sevoflurane were administered. Biochemical and histological evaluations were performed on collected heart and lung tissues. Results: Histological examination of heart tissues showed significantly higher necrosis, polymorphonuclear leukocyte infiltration, edema, and total damage scores in the DIR group compared to controls. These effects were attenuated in fullerenol-treated groups. Lung tissue examination revealed more alveolar wall edema, hemorrhage, vascular congestion, polymorphonuclear leukocyte infiltration, and higher total damage scores in the DIR group compared to controls, with reduced injury parameters in the fullerenol-treated groups. Biochemical analyses indicated significantly higher total oxidative stress, oxidative stress index, and paraoxonase-1 levels in the DIR group compared to the control and diabetic groups. These levels were lower in the fullerenol-treated groups. Conclusions: Distant organ damage in the lung and heart tissues due to lower-extremity ischemia-reperfusion injury can be significantly reduced by fullerenol C60.

The prophylactic and therapeutic effects of cannabidiol on lung injury secondary to cardiac ischemia model in rats via PERK/NRF2/CHOP/BCL2 pathway

Background Inflammation and oxidative stress are key players in lung injury stemming from cardiac ischemia (LISCI). Cannabidiol (CBD) demonstrates tissue-protective properties through its antioxidant, anti-inflammatory, and anti-apoptotic characteristics. This study aims to assess the preventive (p-CBD) and therapeutic (t-CBD) effects of CBD on LISCI. Methods Forty male Wistar Albino rats were divided into four groups: control (CON), LISCI, p-CBD, and t-CBD. The left anterior descending coronary artery was ligated for 30 min of ischemia followed by 30 min of reperfusion. Lung tissues were then extracted for histopathological, immunohistochemical, genetic, and biochemical analyses. Results Histopathologically, marked hyperemia, increased septal tissue thickness, and inflammatory cell infiltrations were observed in the lung tissues of the LISCI group. Spectrophotometrically, total oxidant status and oxidative stress index levels were elevated, while total antioxidant status levels were decreased. Immunohistochemically, expressions of cyclooxygenase-1 (COX1), granulocyte colony-stimulating factor (GCSF), interleukin-6 (IL6) were increased. In genetic analyses, PERK and CHOP expressions were increased, whereas Nuclear factor erythroid 2-related factor 2 (NRF2) and B-cell leukemia/lymphoma 2 protein (BCL2) expressions were decreased. These parameters were alleviated by both prophylactic and therapeutic CBD treatment protocols. Conclusion In LISCI-induced damage, both endoplasmic reticulum and mitochondrial stress, along with oxidative and inflammatory markers, were triggered, resulting in lung cell damage. However, both p-CBD and t-CBD treatments effectively reversed these mechanisms, normalizing all histopathological, biochemical, and PCR parameters.

Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial

BackgroundThis study was designed to examine the effect of resveratrol on mitochondrial biogenesis, oxidative stress (OS), and assisted reproductive technology (ART) outcomes in individuals with polycystic ovary syndrome (PCOS).MethodsFifty-six patients with PCOS were randomly assigned to receive 800 mg/day of resveratrol or placebo for 60 days. The primary outcome was OS in follicular fluid (FF). The secondary outcome involved assessing gene and protein expression related to mitochondrial biogenesis, mitochondrial DNA (mtDNA) copy number, and adenosine triphosphate (ATP) content in granulosa cells (GCs). ART outcomes were evaluated at the end of the trial.ResultsResveratrol significantly reduced the total oxidant status (TOS) and oxidative stress index (OSI) in FF (P = 0.0142 and P = 0.0039, respectively) while increasing the total antioxidant capacity (TAC) (P < 0.0009). Resveratrol consumption also led to significant increases in the expression of critical genes involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) and mitochondrial transcription factor A (TFAM) (P = 0.0032 and P = 0.0003, respectively). However, the effect on nuclear respiratory factor 1 (Nrf-1) expression was not statistically significant (P = 0.0611). Resveratrol significantly affected sirtuin1 (SIRT1) and PGC-1α protein levels (P < 0.0001 and P = 0.0036, respectively). Resveratrol treatment improved the mtDNA copy number (P < 0.0001) and ATP content in GCs (P = 0.0014). Clinically, the resveratrol group exhibited higher rates of oocyte maturity (P = 0.0012) and high-quality embryos (P = 0.0013) than did the placebo group. There were no significant differences between the groups in terms of chemical or clinical pregnancy rates (P > 0.05).ConclusionsThese findings indicate that resveratrol may be a promising therapeutic agent for patients with PCOS undergoing assisted reproduction.Trial registration numberhttp://www.irct.ir; IRCT20221106056417N1; 2023 February 09.

Neohesperidin Dihydrochalcone Ameliorates Experimental Colitis via Anti-Inflammatory, Antioxidative, and Antiapoptosis Effects.

Neohesperidin dihydrochalcone (NHDC) is a citrus-originated, seminatural sweetener. There is no investigation concerning the effect of NHDC on ulcerative colitis. The purpose of this study was to determine the therapeutic and protective effects of NHDC in Wistar Albino rats. NHDC was given for 7 days after or before colitis induction. The results showed that NHDC significantly reduced the interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) levels. Catalase levels did not show a significant difference between the groups. NHDC provided a remarkable decrease in the expression levels of cyclooxygenase-2 (COX-2), myeloperoxidase (MPO), malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and nuclear factor kappa B (NF-κB). Total antioxidant status (TAS) levels were significantly elevated in NHDC treatment groups, while total oxidant status (TOS) and oxidative stress index (OSI) levels were significantly decreased. NHDC provided remarkable improvement in histological symptoms such as epithelial erosion, edema, mucosal necrosis, inflammatory cell infiltration, and hemorrhage. Also, caspase-3 expression levels were statistically decreased in NHDC treatment groups. The results indicated that NHDC might be a protection or alternative treatment for ulcerative colitis.

Effect of Different Administered Doses of Capsaicin and Titanium Implant Osseointegration.

Background and Objectives: This study aimed to evaluate the histological and biochemical effects of capsaicin on implant osseointegration and oxidative stress. Materials and Methods: Male Wistar albino rats weighing between 250 and 300 g were used in this study. Twenty-four rats were randomly divided into three equal groups: implant + control (n = 8), implant + capsaicin-1 (n = 8), and implant + capsaicin-2 (n = 8). Additionally, 2.5 mm diameter and 4 mm length titanium implants were surgically integrated into the corticocancellous bone parts of the femurs. In the treatment groups, rats were injected intraperitoneally with 25 mg/kg (implant + capsaicin-1) and 50 mg/kg (implant + capsaicin-2) of capsaicin. No additional applications were made in the control group. Three rats in total died during and after the experiment as a result of the analyses performed on 21 animals. Results: The highest total antioxidant status value was found in capsaicin dose 2, according to the analysis. The control group had the highest total oxidant status and oxidative stress index values, while group 2 of capsaicin had the lowest. After analysis, we found that there was no observed positive effect on osteointegration in this study (p > 0.05), although the bone implant connection was higher in the groups treated with capsaicin. Conclusions: A positive effect on osteointegration was not observed in this study. This may be due to osteoclast activation. However, it was found that it has a positive effect on oxidative stress. Osteoclast activation may be the cause of this phenomenon. Capsaicin was found to have a positive effect on oxidative stress (p < 0.05). It was also observed to have a positive effect on oxidative stress.

P-501 Superovulation alters telomere length and telomerase expression in mouse oocytes, possibly by changing estradiol and progesterone levels

Abstract Study question How does the single and repeated superovulation affect the telomerase components expression and telomere length in mouse GV and MII oocytes? Summary answer Superovulation significantly altered the expression of the telomerase components Tert and Terc genes, TERT protein levels, and telomere length in the GV and MII oocytes. What is known already Assisted reproductive technologies (ARTs) are commonly used to treat infertility problems. One of the basic ART steps is controlled ovarian stimulation, also known as superovulation. Superovulation can lead to several adverse effects, such as increased oxidative stress, decreased oocyte and embryo quality, and mitochondrial dysfunction. These effects of superovulation largely overlap with those that causing telomere shortening. Study design, size, duration The effect of superovulation on the telomerase expression and telomere length of GV and MII oocytes is not fully addressed yet. In this study, we investigated the potential effects of single and repeated superovulation on telomerase expression and telomere length in mouse oocytes at germinal vesicle (GV) and metaphase II (MII) stages. In addition, we measured the estradiol and progesterone as well as oxidant and antioxidant capacity in serum samples of the oocytes-collected mice. Participants/materials, setting, methods Four groups of female Balb/C mice were formed: Control (C; n = 12), superovulated once (1S; n = 12), superovulated three times (3S; n = 12), and superovulated five times (5S; n = 12) at one-week intervals. The Tert and Terc gene expression, TERT protein levels, and telomere length in the mouse oocytes were assessed by RT-qPCR, immunofluorescence, and q-PCR, respectively. The hormone levels were analyzed by ELISA, and oxidant-antioxidant capacities were measured. All the ovarian follicles were counted in the H&amp;E stained-sections. Main results and the role of chance We found that superovulation (1S, 3S, and 5S) significantly altered expression of the telomerase components Tert and Terc genes, TERT protein levels, and telomere length in the GV and MII oocytes (P&amp;lt;0.05). While estradiol levels in GV oocyte-collected and progesterone levels of GV and MII oocyte-collected mice were higher in the 1S, 3S, and 5S groups compared with the C group (P&amp;lt;0.01), the estradiol levels in MII oocyte-collected mice decreased progressively from C to 5S groups (P&amp;lt;0.01). However, no significant changes were found in the total oxidant status (TOS), antioxidant status (TAS), and oxidative stress index (OSI) between the groups. Also, primordial and atretic follicle numbers in the ovaries of 3S and 5S groups were significantly decreased compared to the control and 1S groups (P&amp;lt;0.05). Limitations, reasons for caution The limitation of this study is that we could not evaluate telomerase activity and oxidative stress levels in the mouse oocytes. Wider implications of the findings All these results suggest that altered telomerase expression and telomere length in GV and MII oocytes, possibly due to changed estradiol and progesterone levels, may be associated with adverse effects of superovulation on oocyte maturation and even preimplantation embryo development. Trial registration number not applicaple

Protective effects of E-CG-01 (3,4-lacto cycloastragenol) against bleomycin-induced lung fibrosis in C57BL/6 mice

Idiopathic pulmonary fibrosis is an aging-related, chronic lung disease, with unclear pathogenesis and no effective treatment. One of the triggering factors in cell aging is oxidative stress and it is known to have a role in idiopathic pulmonary fibrosis. In this paper, the protective effect of the E-CG-01 (3,4-lacto-cycloastragenol) molecule in terms of its antioxidant properties was evaluated in the bleomycin induced mice lung fibrosis model. Bleomycin sulfate was administered as a single dose (2.5 U/kg body weight) intratracheally to induce lung fibrosis. E-CG-01 was administered intraperitoneally in three different doses (2 mg/kg/day, 6 mg/kg/day, and 10 mg/kg/day) for 14 days, starting three days before the bleomycin administration. Fibrosis was examined by Hematoxylin-Eosin, Masson Trichrome, and immunohistochemical staining for TGF-beta1, Type I collagen Ki-67, and gama-H2AX markers. Activity analysis of catalase and Superoxide dismutase enzymes, measurement of total oxidant, total glutathione, and Malondialdehyde levels. In histological analysis, it was determined that all three different doses of the molecule provided a prophylactic effect against the progression of fibrosis compared to the bleomycin control group. However, it was observed that only the molecule applied in the high dose decreased the total oxidant stress level. Lung weight ratio increased in the BLM group but significantly reduced with high-dose E-CG-01. E-CG-01 at all doses reduced collagen deposition, TGF-β expression, and Ki-67 expression compared to the BLM group. Intermediate and high doses of E-CG-01 also significantly reduced alveolar wall thickness and edema formation. These findings suggest that E-CG-01 has potential therapeutic effects in mitigating lung fibrosis through its antioxidant properties.

Serum Total Bilirubin and Oxidative Stress Status in Diabetic Retinopathy – A Hospital-Based Observational Study

Diabetic retinopathy (DR) is one of the common microvascular complications of Type 2 Diabetes Mellitus (T2DM). As an antioxidant, the serum total bilirubin is associated with vaso-occlusive disorders. Oxidative stress parameters such as Erythrocyte Glutathione (GSH) as an antioxidant and Malondialdehyde (MDA) as an oxidant are critical in the pathogenesis of diabetic complications. This study aimed to explore the possibilities of the endogenous protective role of serum total bilirubin on the retinal vasculature in DR patients by estimating and correlating the levels of serum total bilirubin, GSH, and MDA in DR cases. In this hospital-based case-control study, 288 participants were selected from R.L. Jalappa Hospital and Research Centre, Kolar, divided into three groups with 96 subjects per group. Group I: Controls, Group II: T2DM, and Group III: DR subjects. The fasting blood sugar, glycated hemoglobin, liver function test, and lipid profiles were estimated by standard methods. Oxidative stress parameters viz, GSH and MDA were assayed by chromogen 5,5'- di thiobis 2-nitrobenzoic acid (DTNB) and thiobarbituric acid reactive substances (TBARS) methods, respectively. The prevalence of DR was significantly lower among subjects with the highest bilirubin quartile than those with the lowest. There was a significant mean difference with p&lt;0.001 between the groups for total bilirubin, FBS, HbA1c, GGT, TC, TG, LDL, GSH, and MDA. A Negative correlation of serum total bilirubin with FBS (r = - 0.375), HbA1c (r = -0.351), and MDA(r=-0.323), and a positive correlation with GSH (r = 0.335) was observed in DR group with a significant p-value. T2DM subjects with higher levels of bilirubin within biological reference intervals were less likely to develop retinopathy. The severity of DR was inversely proportional to the total bilirubin levels. Therefore, serum total bilirubin levels could be a biomarker to predict the risk of developing retinopathy in people with T2DM.