GSH Levels Research Articles

Minimizing Oxidative Stress in the Lens: Alternative Measures for Elevating Glutathione in the Lens to Protect against Cataract.

Oxidative stress plays a major role in the formation of the cataract that is the result of advancing age, diabetes or which follows vitrectomy surgery. Glutathione (GSH) is the principal antioxidant in the lens, and so supplementation with GSH would seem like an intuitive strategy to counteract oxidative stress there. However, the delivery of glutathione to the lens is fraught with difficulties, including the limited bioavailability of GSH caused by its rapid degradation, anatomical barriers of the anterior eye that result in insufficient delivery of GSH to the lens, and intracellular barriers within the lens that limit delivery of GSH to its different regions. Hence, more attention should be focused on alternative methods by which to enhance GSH levels in the lens. In this review, we focus on the following three strategies, which utilize the natural molecular machinery of the lens to enhance GSH and/or antioxidant potential in its different regions: the NRF2 pathway, which regulates the transcription of genes involved in GSH homeostasis; the use of lipid permeable cysteine-based analogues to increase the availability of cysteine for GSH synthesis; and the upregulation of the lens's internal microcirculation system, which is a circulating current of Na+ ions that drives water transport in the lens and with it the potential delivery of cysteine or GSH. The first two strategies have the potential to restore GSH levels in the epithelium and cortex, while the ability to harness the lens's internal microcirculation system offers the exciting potential to deliver and elevate antioxidant levels in its nucleus. This is an important distinction, as the damage phenotypes for age-related (nuclear) and diabetic (cortical) cataract indicate that antioxidant delivery must be targeted to different regions of the lens in order to alleviate oxidative stress. Given our increasing aging and diabetic populations it has become increasingly important to consider how the natural machinery of the lens can be utilized to restore GSH levels in its different regions and to afford protection from cataract.

The Growth Inhibitory Effect of Resveratrol and Gallic Acid on Prostate Cancer Cell Lines through the Alteration of Oxidative Stress Balance: The Interplay between Nrf2, HO-1, and BACH1 Genes.

The association between oxidative stress and prostate cancer (PC) has been demonstrated both epidemiologically and experimentally. Balance in reactive oxygen species (ROS) levels depends on multiple factors, such as the expression of Nrf2, HO-1, and BACH1 genes. Natural polyphenols, such as resveratrol (RSV) and gallic acid (GA), affect cellular oxidative profiles. The present study investigated the possible effects of GA and RSV on the oxidative profiles of PC3 and DU145 cells, as well as Nrf2, HO-1, and BACH1 gene expression to achieve an understanding of the mechanisms involved. PC3 and DU145 cells were treated with ascending concentrations of RSV and GA for 72 h. Then cell growth and mRNA expression of Nrf2, HO-1, and BACH1 genes were analyzed by real-time PCR. Various spectrophotometric analyses were performed to measure oxidative stress markers. RSV and GA significantly decreased the growth of PC3 and DU145 cells compared to the control group in a concentration-dependent manner. RSV and GA also decreased ROS production in PC3 cells, but in DU145 cells, only the latter polyphenol significantly decreased ROS content. In addition, RSV and GA had ameliorating effects on SOD, GR, GPX, and CAT activities and GSH levels in both cell lines. Also, RSV and GA induced HO- 1 and Nrf2 gene expression in both cell lines. BACH1 gene expression was induced by RSV only at lower concentrations, in contrast to GA in both cell lines. Our data suggest that RSV and GA can prevent the growth of prostate cancer cells by disrupting oxidative stress-related pathways, such as changes in Nrf2, HO-1, and BACH1 gene expression.

Brain mitochondrial damage attenuation by quercetin and N-acetyl cysteine: peripheral and central antiemetic effects.

Nausea serves as a protective mechanism in organisms to prevent excessive consumption of toxic substances. Due to the adverse effects of chemical anti-nausea drugs, there is a growing interest in using herbal remedies and natural antioxidants. In this study, we evaluated the neuroprotective effects of quercetin (QU) and N-acetylcysteine (NAC) against oxidative damage induced by nausea. Emesis was induced in chickens using ipecac and copper sulfate (600 and 60mg/kg, orally, respectively). QU and NAC (with doses of 50, 100, 200mg/kg), and their combination were administered, along with a standard therapy (metoclopramide; MET 2mg/kg) for one-time. Mitochondrial function, lipid peroxidation (LPO), protein carbonyl (PC), glutathione level (GSH), and reactive oxygen species (ROS) as oxidative damage biomarkers were evaluated in the chicken's brain mitochondria. QU and NAC significantly reduced emesis induced by copper sulfate and ipecac compared to the control group (P<0.001). Significant differences in oxidative damage were observed in the groups received of copper sulfate and ipecac compared with control group. Levels of LPO, ROS, and PC were significantly decreased after the administration of QU and NAC in emesis induced by copper sulfate and ipecac. While, mitochondrial function and GSH levels were increased after the administration of QU and NAC. Combination therapy with QU and NAC yielded the most effective results. This study suggests that QU and NAC possess antiemetic effects through both peripheral and central mechanisms and exhibit neuroprotective effects against oxidative brain damage induced by emesis by increasing plasma antioxidants or scavenging free radicals.

Yap1 alleviates sepsis associated encephalopathy by inhibiting hippocampus ferroptosis via maintaining mitochondrial dynamic homeostasis.

Sepsis-associated encephalopathy (SAE) is a serious neurological complication accompanied by acute and long-term cognitive dysfunction. Ferroptosis is a newly discovered type of cell death that is produced by iron-dependent lipid peroxidation. As a key transcriptional coactivator in the Hippo signalling pathway, Yes-associated protein 1 (YAP1) could target ferroptosis-related genes. This study was aimed to determine whether Yap1 protects against SAE and inhibits ferroptosis via maintaining mitochondrial dynamic homeostasis. Caecal ligation puncture (CLP) was used to establish the SAE model, and LPS was applied in hippocampal cells to mimic the inflammatory model invitro. The results showed that Yap1 conditional knockout in hippocampal caused lower survival in SAE mice and cognitive dysfunction, as proved by Morri's water maze (MWM) task, tail suspension test (TST), open field test (OFT) and elevated plus maze test (EPMT). After Yap1 knockout, the production of ROS, MDA and Fe2+ and proinflammatory cytokines in the hippocampus were increased, indicating that Yap1 deficiency exacerbates CLP-induced brain injury and hippocampus ferroptosis. Meanwhile, GPX4, SLC7A11, ferritin (FTH1) and GSH levels were decreased in the Yap1 knockout group. Invitro, Yap1 overexpression mitigated LPS-induced hippocampal cell ferroptosis and improved mitochondrial function by inhibiting mitochondrial fission, as evidenced by lower mitochondrial ROS, cell viability, Fe2+ and the expression of Fis1 and Drp1. Further, the present study suggested that Yap1 could inhibit ferritinophagy-mediated ferroptosis in the hippocampus via inhibiting mitochondrial fission, thus reducing cognitive dysfunction in SAE mice.

Caffeic acid inhibits Staphylococcus aureus-induced endometritis through regulating AMPKα/mTOR/HIF-1α signalling pathway.

Endometritis is mostly caused by childbirth or postpartum uterine infection. It is one of the important reasons leading to female infertility. Caffeic acid (CA) and its derivatives are widely found in some foods and traditional Chinese medicine, and have biological activities such as antioxidant, free radical scavenging, anti-inflammatory, and anti-infection. In this study, we aimed to explore the effect of CA on Staphylococcus aureus-induced endometritis. The contents of TNF-α and IL-1β were detected by ELISA in S. aureus-induced endometritis model. Western blot assay was used to detect the expression of AMPKα/mTOR/HIF-1α pathway related proteins and GPX4 expression. In addition, the concentrations of MDA, GSH, and iron were tested by the assay kits. Compared with the model group, CA treatment significantly alleviated S. aureus-induced uterine injury, MPO activity, the contents of inflammatory factors TNF-α and IL-1β, and NF-κB activation. Meanwhile, CA significantly inhibited S. aureus-induced ferroptosis, as confirmed by decreased MDA and iron concentration and up-regulated GPX4 expression and GSH level. Furthermore, CA attenuated S. aureus-induced HIF-1α and phosphorylated mTOR expression and increased phosphorylated AMPK expression. In conclusion, CA inhibits inflammation and ferroptosis by regulating AMPKα/mTOR/HIF-1α signalling pathway to alleviate S. aureus-induced endometritis in mice.

USP4/CARM1 Axis Promotes the Malignant Transformation of Breast Cancer Cells by Upregulating SLC7A11 Expression

BackgroundCoactivator associated arginine methyltransferase 1 (CARM1) has been identified as a regulator of breast cancer (BC) progression, yet the underlying mechanisms remain elusive. MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the mRNA expression of CARM1 and solute carrier family 7 member 11 (SLC7A11). Western blotting was conducted to detect the protein expressions of CARM1, ubiquitin specific peptidase 4 (USP4), and SLC7A11. Cell viability, apoptosis, invasion, and migration were evaluated using CCK-8 assay, flow cytometry, transwell assay, and wound-healing assay, respectively. Fe2+ and GSH levels were determined by colorimetric assay. Fluorescence microscopy and flow cytometry were utilized to quantify reactive oxygen species (ROS) production. Co-immunoprecipitation (Co-IP) assay and cycloheximide (CHX) assay were performed to investigate the relationship between USP4 and CARM1. Xenograft mouse model assay was conducted to validate the effects of USP4 silencing and CARM1 overexpression on the malignant phenotypes of BC cells. ResultsCARM1 and SLC7A11 expression was upregulated in BC tissues and cells when compared with normal breast tissues and cells. Silencing of CARM1 inhibited the malignant phenotypes of BC cells, including decreased cell viability, invasion, and migration and increased cell apoptosis, ferroptosis and oxidative stress. In addition, USP4 stabilized CARM1 protein expression through its deubiquitinating activity. Overexpression of CARM1 attenuated the effects of USP4 silencing in both MCF-7 and MDA-MB-231 cells. Furthermore, silencing of CARM1 reduced SLC7A11 expression, and SLC7A11 overexpression relieved the CARM1 silencing-induced effects. Further, overexpression of CARM1 counteracted the inhibitory effects of USP4 silencing on tumor growth in vivo. ConclusionOur study reveals a novel mechanism by which USP4-dependent CARM1 promotes the malignant growth of BC cells by interacting with SLC7A11. Targeting this axis may provide a potential therapeutic strategy for BC.

Ethanolic and aqueous extracts of Lantana camara show antiepileptic and anxiolytic effects by inhibiting the ferroptosis pathway in kainate-treated mice

In Cameroon, epilepsy is one of the most common neurological diseases. Available anti-epileptic medication, on the other hand, have been associated with pharmacological toxicity and emotional impairment. The identification of a more efficient replacement is critical. Recent research reveals that ferroptosis contributes to the pathophysiology of epilepsy and related anxiety disorders. Lantana camara is a plant with a high neuropharmacological potential, but its mechanisms of action have yet to be understood. The purpose of this study was to determine the effect of ethanolic and aqueous extracts of Lantana camara on the kainate model of epilepsy in mice. The focus was on these extracts' capacity to suppress ferroptosis. Mice were injected with kainate (12 mg/kg, i.p.) to induce epilepsy. After status epilepticus, animals were left for 19 days, which correspond to an epileptogenic period. After the appearance of spontaneous recurrent seizures, mice were treated with distilled water (10 ml/kg, p.o.), levetiracetam (80 mg/kg, p.o.), sodium valproate (300 mg/kg, p.o.), ethanolic extract of L. camara (230, 460, 920 mg/kg, p.o.), or an aqueous extract of L. camara (460 mg/kg p.o.). These treatments lasted for 14 days. During this period, the number and duration of seizures were recorded. The mice were then subjected to elevated zero-maze and open field tests to assess anxiety-like behavior. At the end, mice were sacrificed and hippocampus, amygdala, and striatum were dissected out for biochemical and histological analyses. The extracts alleviated seizure- and anxiety-like behavior in KA-treated mice. Decreased iron levels, reflected by a decrease in ferritin levels and a increase in transferrin levels, were observed in the hippocampus, striatum and amygdala of the extract-treated group compared to the KA-treated group. In addition, increase in GABA and GSH levels, and a decrease in MDA levels were observed in these groups. Hematoxylin-eosin staining revealed less pronounced neuronal degeneration and a more sustained architecture in the brain region of extract-treated mice. These findings indicated that ethanolic and aqueous extracts of L. camara effectively attenuate seizures and anxiety disorders. Probable mechanisms of action include GABAergic, iron, GSH, and MDA modulations.

Exploring the Mechanism of Action of Sericin in Ameliorating non-Alcoholic Fatty Liver Disease in Mice Based on the Nrf2- GPX4/ NF-κB p65 Pathway

Objective: To explore the ameliorative effect and mechanism of action of sericin on liver injury in Non-Alcoholic Fatty Liver Disease (NAFLD) model mice. Methods: Mice were fed a high-fat diet for 8 weeks to establish NAFLD model mice. The NAFLD mice were then randomly divided into 6 groups and given 0, 250, 500, and 1000 mg/kg body weight of sericin, 1000 mg/kg sericin + ML385 (a protein inhibitor of Nrf2), and Zhibitai Capsules (a positive drug), by gavage, respectively. The levels of TC, TG, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in mouse serum and the levels of MDA, GSH, SOD, TNF-α, and IL-6 in liver tissues were measured. Pathological changes in liver tissues were evaluated using hematoxylin-eosin (HE) and Oil Red O staining. Protein expression of Nrf2, Keap1, HO-1, GPX4, and NF-κB p65 in liver tissues was detected by Western blotting, and the expression level of GPX4 in the liver was examined by immunohistochemistry. Results: Sericin and Zhibitai Capsules improved hepatic steatosis and lipid accumulation in NAFLD model mice. TC, TG, LDL-C, MDA, and TNF-α, IL-6 levels were down-regulated, and HDL-C and SOD levels were up-regulated. There was no significant difference in the expression of AST and ALT in all the groups. In addition, Sericin and Zhibitai Capsules upregulated the expression levels of Nrf2, keap1, HO-1, and GPX4 proteins and inhibited the expression of NF-κB p65 in the liver of NAFLD model mice. There was no significant difference in serum lipids and liver indices between the 1000 mg/kg sericin + ML385 group and the sericin dose groups. Conclusion: Sericin has an ameliorative effect on liver injury in NAFLD model mice by alleviating oxidative stress and inflammatory responses in liver injury. It remains to be explored whether this effect is regulated through the Nrf2- GPX4/ NF-κB p65 signaling pathway.

Early prediction of maize resistance to nicosulfuron using hyperspectral imaging and deep learning: Method and mechanism

Inappropriate use of herbicides in agricultural fields can result in significant phytotoxic effects on maize, adversely affecting both yield and quality. The development of herbicide-resistant maize varieties is a crucial strategy for managing herbicide-related challenges in agriculture. However, traditional methods for screening resistant strains are often time-consuming and inefficient, presenting several limitations. Consequently, there is a pressing need for a rapid and precise methodology to evaluate herbicide resistance in maize. This study involved a field trial to evaluate herbicide resistance in maize, utilizing two resistant and two sensitive varieties. We developed an ATT-RES model using hyperspectral data from maize leaves subjected to herbicide stress to predict resistance. The model’s accuracy and generalizability were confirmed by integrating datasets across different years, planting seasons, and varieties. Additionally, this study examined the correlation between leaf spectra and corresponding physiological and biochemical indicators under herbicide stress by constructing a regression model and investigated the mechanisms through which spectra can predict herbicide resistance in maize. The findings indicate that on the fourth day after herbicide treatment, the model’s predictive accuracy exceeded 90 %. The accuracy peaked on the seventh day, achieving up to 95 %. The ATT-RES-based transfer model attained prediction accuracy of 93.55 %, 90.63 %, and 95.86 % across various years, varieties, and seasons, respectively. The results presented here offer significant advantages over traditional models such as Support Vector Machines (SVM), Multilayer Perceptrons (MLP), and AlexNet. Furthermore, we employed Partial Least Squares Regression (PLSR) to analyze the relationship between leaf physiological-biochemical parameters and spectral data. The analysis revealed significant correlations between the spectra and key biochemical markers: glutathione (GSH, Rp2 = 0.59), malondialdehyde (MDA, Rp2 = 0.48), chlorophyll content (SPAD, Rp2 = 0.82), and water content (WC, Rp2 = 0.71). The prediction of resistance was primarily influenced by variations in leaf SPAD and WC, but also showed correlations with GSH and MDA levels in the leaves. This study contributes valuable theoretical and technological insights that facilitate early and precise prediction of herbicide resistance in maize. The advancements demonstrated in this research hold significant potential for improving crop management and reducing the adverse impacts of herbicides on the environment.

In vivo assessment of oxidative stress, neurotoxicity and histological alterations induction in the marine gastropod Stramonita haemastoma exposed to Cr2O3 and Al2O3 nanoparticles

The increased use of nanoparticles (NPs) is expected to raise their presence in the marine ecosystem, which is considered as the final destination of released NPs. This study investigated the toxicity of Cr2O3 (42 nm) and Al2O3 (38 nm) NPs (1, 2.5, and 5 mg/L) on the digestive glands of Stramonita haemastoma for 7, 14, and 28 days by oxidative stress biomarkers, neurotoxicity indicator assessment, and histological study. Results revealed an imbalance in antioxidants at all periods. Following 7 days, both NPs caused GSH depletion with marked impacts from Al2O3. GPx, CAT, and AChE were also decreased with the highest changes induced by Cr2O3. Both NPs inducted GSH and GST levels on days 14 and 28, with more effects from Cr2O3 exposure. GPx, AChE, and MDA induction were observed on day 28, while MT varied through NPs and time, with imbalanced levels at all periods noticed, SOD was mostly not affected. Histology revealed alterations including necrosis and interstitial deteriorations; quantitative analysis through the histological condition index revealed dose-dependent impacts, with the highest values attributed to Cr2O3 exposure. While PCA revealed the co-response of GSH, GST, GPx, CAT, and AchE with separated MT responses. This study reported oxidative stress induction through a multi-biomarkers investigation, neurotoxicity, and histological damages in the digestive gland of S. haemastoma following Cr2O3 and Al2O3 NPs exposure.

Changes in Oxidative Stress Markers in Pregnant Women of Advanced Maternal Age with Gestational Diabetes and Their Predictive Value for Neurodevelopmental Impact.

To explore the relationship between changes in oxidative stress markers in pregnant women of advanced maternal age with gestational diabetes mellitus (GDM) and adverse pregnancy outcomes and neonatal neurodevelopment, as well as their predictive value. Two hundred pregnant women of advanced maternal age were selected and divided into Group A (normal blood sugar) and Group B (GDM) based on the 75 g (Oral Glucose Tolerance Test) OGTT results. Oxidative stress markers were measured, and pregnancy outcomes and neonatal Neonatal Behavioral Assessment Scale (NABA) scores were recorded. Malondialdehyde (MDA) levels in Group B were higher than those in Group A, while Glutathione (GSH) and Superoxide Dismutase (SOD) levels were lower. Group B had higher rates of adverse pregnancy outcomes and neurological abnormalities than Group A. The Area Under the Curve (AUC) values for serum MDA, GSH, and SOD levels combined prediction were higher than those for individual predictions (P<0.05). Oxidative stress markers in pregnant women of advanced maternal age with GDM are associated with adverse pregnancy outcomes and neonatal abnormalities, and combined prediction has good predictive efficiency (AUC>0.7).

Evaluation of SO2, glutathione, and glutathione-rich inactive dry yeast as antioxidants on the fermentation properties of Roxburgh rose wine

Cili (Roxburgh rose) wine, which is rich in ascorbic acid, flavones, and polyphenols, presents unique challenges in wine production, including oxidation, aroma loss, and SO2 residues. This study investigated the effects of three antioxidants (SO2, glutathione (GSH), and GSH-rich inactive dry yeast (g-IDY)) on the fermentation properties of cili wine and evaluated the potential of g-IDY for addressing the aforementioned issues. g-IDY significantly enhanced the fermentation rate, as evidenced by increased CO2 production within 48 h, and maintained high levels of GSH, total phenolics, total flavones, and ascorbic acid, contributing to the antioxidant capacity and overall stability of the wine. g-IDY also improved the retention and concentration of key aromatic compounds, including higher alcohols, esters, and terpenes, thereby enhancing the sensory profile of the wine. Principal component analysis confirmed that different antioxidants significantly altered the volatile profile, with g-IDY demonstrating distinct improvements. The optimal concentration was 400 mg/L g-IDY. Compared with traditional antioxidants like SO2 and pure GSH, g-IDY offers a safer and more effective solution for preserving the quality of cili wine. This study provides experimental evidence for refining the fermentation process and promotes the use of g-IDY for enhancing the antioxidant capacity and sensory attributes of cili wine.

Atractylenolide II regulates the proliferation, ferroptosis, and immune escape of hepatocellular carcinoma cells by inactivating the TRAF6/NF-κB pathway.

Hepatocellular carcinoma (HCC) is a common and lethal tumor worldwide. Atractylenolide II (AT-II) is a natural sesquiterpenoid monomer, with anti-tumor effect. To address the effect and mechanisms of AT-II on HCC. The role and mechanisms of AT-II were assessed through cell counting kit-8, flow cytometry, enzyme-linked immunosorbent assay, immunofluorescence, and western blot experiments in Hep3B and Huh7 cells. In vivo experiments were conducted in BALB/c nude mice using immunohistochemistry and western blot assays. AT-II decreased the cell viability of Hep3B and Huh7 cells with a IC50 of 96.43 µM and 118.38 µM, respectively. AT-II increased relative Fe2+ level, which was further promoted with the incubation of erastin and declined with the ferrostatin-1 in Hep3B and Huh7 cells. AT-II enhanced the level of ROS and MDA, but reduced the GSH level, and the expression of xCT and GPX4. AT-II elevated the percent of CD8+ T cells and the IFN-γ contents, and declined the IL-10 concentrations and the expression of PD-L1 in Hep3B and Huh7 cells. AT-II downregulated the relative protein level of TRAF6, p-p65/p-65, and p-IkBα/IkBα, which was rescued with overexpression of TRAF6. Upregulation of TRAF6 also reversed the effect of AT-II on proliferation, ferroptosis, and immune escape in Hep3B cells. In vivo, AT-II reduced tumor volume and weight, the level of GPX4, xCT, and PD-L1, and the expression of TRAF6, p-p65/p-65, and p-IkBα/IkBα, with the increased expression of CD8. AT-II modulated the proliferation, ferroptosis, and immune escape of HCC cells by downregulating the TRAF6/NF-κB pathway.

Betaine and B12 Intake, Glutathione Concentration, and MTHFR, PEMT, and MTHFD1 Genotypes Are Associated with Diabetes-Related Parameters in Polish Adults

BackgroundThere is a growing body of evidence on associations between one-carbon metabolism (OCM) and diabetes-related parameters. For this reason, we aimed to examine the associations of plasma choline, betaine, trimethylamine N-oxide (TMAO), glutathione (GSH), serum folate, vitamin B12, dihydrofolate reductase (rs70991108) genotype, methylenetetrahydrofolate reductase (MTHFR) (rs180113) genotype, methylenetetrahydrofolate dehydrogenase (MTHFD1) (rs2236225) genotype, and phosphatidylethanolamine N-methyltransferase (rs7946 and rs12325817) genotype with fasting glucose level, insulin level, and diabetes-related indices. MethodsThe study group consisted of 421 Polish adults aged 20–40 y. Food intake was assessed using a 3-d food diary. Plasma concentrations of choline, betaine, and TMAO were determined by ultra-high-performance liquid chromatography-electrospray ionization mass spectrometry. The total plasma GSH level was measured by high-performance liquid chromatography. Insulin, folate, and vitamin B12 concentrations were estimated by enzyme-linked immunosorbent assay method. Genotyping was performed with TaqMan probes. ResultsGSH level was negatively associated with insulin (β = −0.11, P < 0.05) and gamma-glutamyl transferase (GGTP) (β = −0.12, P < 0.05), and positively associated with fasting glucose (β = 0.11, P < 0.05). Betaine intake was negatively associated with serum insulin concentration (β = −0.13, P < 0.05) and HOMA-IR (β = −0.12, P < 0.05). Choline intake was negatively associated with insulin (β = −0.17, P < 0.01). Serum folate level was negatively associated with GGTP (β = −0.11; P < 0.05). The methylenetetrahydrofolate reductase (MTHFR) CC genotype was associated with higher serum insulin levels (β = 0.15; P < 0.01) and higher HOMA-IR (β = 0.15, P < 0.01), whereas the MTHFD1 AA genotype was negatively associated with Quantitative Insulin Sensitivity Check Index (β = −0.11, P < 0.05). ConclusionsOur findings suggest that higher GSHL and higher intake of betaine, B12, and choline, as well as the TT genotype of MTHFR and the AA genotype of MTHFD1, are associated with lower diabetes-related parameters among adults.

Oleic Acid Inhibits SDC4 and Promotes Ferroptosis in Lung Cancer Through GPX4/ACSL4.

As a common malignancy, lung cancer has a relatively poor prognosis and a low survival rate. In recent years, ferroptosis, as an emerging filed, has great promise in the potential treatment of cancer. Brucea javanica oil (BJO) is often used to treat various cancers. Oleic acid (OA) is the main ingredient of BJO. In this study, we investigated the role and molecular mechanism of OA in lung cancer treatment by promoting ferroptosis. In this study, A549 cells and H1299 cells were used for invitro experiments, and a CCK-8 test, scratch test, and MTT experiment were carried out. We examined reactive oxygen species (ROS), the JC-1 probe, glutathione (GSH) expression, lipid peroxidation, SDC4 mRNA levels, and ACSL4, SLC7A11, GPX4, and SDC4 protein levels. The results showed that OA could inhibit the proliferation and migration of A549 cells and H1299 cells, SDC4 was a potential therapeutic target of OA against lung cancer, and OA treatment significantly inhibited the expression of SDC4 in A549 cells and H1299 cells. OA induces ferroptosis in A549 cells and H1299 cells, decreases GSH levels, increases lipid peroxidation levels, and decreases SDC4 mRNA expression; in addition, OA upregulates ACSL4 expression and decreases SLC7A11, GPX4, and SDC4 expression. This study confirmed that OA could inhibit SDC4 expression and promote the occurrence of ferroptosis in A549 cells and H1299 cells through the GPX4/ACSL4 pathway, providing an effective basis for the use of drugs targeting ferroptosis in lung cancer treatment.

Protective Effect of Chlorogenic Acid Against Testicular Damage Induced By Glyphosate Isopropilamine in Rats

The aim of this subchronic toxicity study was to determine the prophylactic effect of chlorogenic acid (CGA) on the histopathologic-histologic changes and oxidative stress induced by Glyphosate isopropylamine (GLF-ISO) in testicular tissues. A sum of 42 male Wistar rats were divided into six equal groups, each containing 7 rats. For pretreatment, rats were given CGA at doses of 12.5, 25 and 50 mg/kg (po) and GLF-ISO at 787.85 mg/kg (po) for 7 weeks. GLF-ISO significantly increased malondialdehyde levels while decreasing SOD and CAT activities and GSH levels in testicular tissues. On the contrary, these parameters were improved in CGA-treated groups. Furthermore, CGA ameliorated the histopathological and histological changes in testicular tissues induced by GLF-ISO in a dose-dependent manner. The results indicate that testicular damage caused by GLF-ISO can potentially be prevented or managed by CGA.

Lactoferrin alleviates gentamicin-induced acute kidney injury in rats by suppressing ferroptosis: Highlight on ACSL4, SLC7A11, NCOA4, FSP1 pathways and miR-378a-3p, LINC00618 expression

The use of gentamicin (GNT) is associated with acute kidney injury (AKI). Ferroptosis is a newly recognized iron-dependent, non-apoptotic cell death that can lead to AKI. Lactoferrin (LF), an iron-binding glycoprotein, was previously reported to be renoprotective. Nonetheless, LF's impact on GNT-induced AKI and ferroptosis has not yet been investigated. Accordingly, we assessed the dose-dependent effect of LF on GNT-induced AKI and its influence on ferroptosis. Thirty-six male rats were allocated as control, LF, GNT (100 mg/kg/day, i.p.), and groups given LF (100, 200, and 300 mg/kg, p.o.) for 14 days prior concurrently with GNT (Day 8–14). The high dose of LF (300 mg/kg) showed better histopathological picture, higher creatinine clearance, reduced serum and urine levels of kidney injury markers when compared to the GNT group and the lower two doses. These nephroprotective effects of LF can be attributed to the observed reduction in renal ferrous iron, 4-HNE, and MDA, miR-378a-3p and ALOX15 expression, TFR1, NCOA4, and ACSL4 protein expression and the increased LINC00618 expression, GSH levels, GPX4, SLC7A11, and FSP1 protein expression. In conclusion, LF high dose was the most renoprotective against GNT-induced AKI, in which suppression of ferroptosis pathways was a likely contributor to its protective mechanism.

Effect of Synthetic Wastewater on Antioxidant Defence System in Dreissena polymorpha

The effects of the synthetic wastewater on antioxidant defence system in Dreissena polymorpha evaluated. For this purpose, SOD, CAT, GPX activities and TBARS and GSH levels in tissues were determined by using commercial kits. The activities of SOD and CAT were in sythtetic group were determined lower than the control group in D. polymorpha during 24 and 96 h (p

Potential nephroprotective effect of dapagliflozin against renal ischemia reperfusion injury in rats via activation of autophagy pathway and inhibition of inflammation, oxidative stress and apoptosis

Renal ischemia/reperfusion injury is a common cause of acute kidney injury (AKI), causing tissue damage, inflammation and oxidative stress. Autophagy, responsible for breakdown and recycling of cytoplasmic components. In hypoxic and ischemic renal damage, autophagy may serve as a survival strategy for the cells. Dapagliflozin has been shown to have protective effects against ischemia. Objective: The study investigates the potential nephro-protective effects of dapagliflozin on renal ischemia reperfusion injury, evaluating its antioxidant, anti-inflammatory, anti-apoptotic effects and activation of autophagy via biochemical parameters and histopathological changes in adult male rats. Material and method: In this study, twenty eight male rats weighing between 200-300g, were divided into 4 groups sham, RIRI, DMSO, Dapagliflozin pretreated groups. All groups subjected to 30 min. of ischemia then 24 h of reperfusion except sham undergo the same anesthesia and surgical procedures except for bilateral renal ischemia. Dapagliflozin 1mg/kg and DMSO was given 2 hours before the induction of ischemia. Results: The study found that blood urea and serum creatinine levels increased in RIRI and DMSO groups when compared with sham group. Renal tissue levels of IL-6, Kim-1, caspase-3, LC-3 and Akt were also elevated in RIRI while GSH levels decreased in the RIRI. Dapagliflozin group showed significant increases in GSH, LC-3 and Akt levels when compared to sham group. Dapagliflozin reduced serum urea and creatinine levels, and renal tissue levels of IL-6, Kim-1, and caspase-3 also reduced. Conclusion: Dapagliflozin significantly reduced renal damage in rat model due to its antioxidant, anti-inflammatory, anti-apoptotic, and activation autophagy.

Glutaredoxin-1 and Others Antioxidants Enzymes in Two Subtypes (B-cell and T-cell) of Acute Lymphoblastic Leukemia Patients

The 5-year event-free viability for acute lymphoblastic leukemia (ALL) have enhanced in many study groups due to modern paediatric clinical trials, however T-cell ALL results are still lagging by 5–10% in most studies. The goal of this study was to measure the Glutaredoxin-1(Grx1) as an antioxidant, and also to measure each of the methionine sulfoxide reductaseA(MsrA),myeloperoxidase(MPO), catalase(CAT), xanthine oxidase(XO), glutathione (GSH), albumin (Alb), and complete blood counts (CBC) in two subtypes (B-cell and T-cell) of ALL patients compared with control group between the ages of two and fifteen years. Revealed with the results of this study, Grx1, CAT, MDA levels increased statistically significantly in two subtypes of acute lymphocytic leukemia Patients compared with control group, but MsrA, GSH, Alb, and CBC levels declined considerably in two subtypes for patients compared with control group. Finally MPO have non-significant difference in compared.The study concluded that there was a high increase in the level of Grx1, which participates in rescuing blood components from the process of breakdown in which a decrease was observed n for two subtypes (B-cell and T-cell), in addition to a decrease in MsrA, GSH, which works to repair the damage occurring in the proteins of cell components, including blood components, malignant B cells are particularly sensitive in contrast to the T cell.