Glutathione Peroxidase Research Articles

Dietary antioxidants: An overview

The substances which inhibit oxidation are called as antioxidants. They are also known as free radical scavengers. The decrease in concentration of antioxidant is termed as oxidative stress. The presence of antioxidants decreases the risk of inflammation, liver disease, cardiovascular, cataract, nephrotoxicity and neurodegenerative diseases. They are categorized as exogenous and endogenous. Endogenous antioxidants include enzymatic and non-enzymatic. Enzymatic antioxidants are glutathione peroxidase, superoxide dismutase and catalase whereas non-enzymatic are uric acid, metanonin lipoic acid, glutathione and bilirubin. Exogenous are carotenoids, Vitamin E, A, C and flavonoids. Apart from natural antioxidants, synthetic antioxidants such as octyl gallate, butylated hydroxyanisole, propyl gallate, hydroxytoluene and tertbutylhydroquinone are used to enhance flavor, color extending shelf life of the product. This paper discusses on the various role of antioxidants.

Antioxidant and anti-inflammatory potential of vanillic acid improves nephrotoxicity induced by sodium arsenite in mice

ABSTRACT This study examined the potential of vanillic acid (VA) to protect against renal oxidative stress and inflammation caused by sodium arsenite (SA) in mice. Mice were assigned to five groups: control, VA (100 mg/kg), SA (50 ppm in drinking water for 8 weeks), and SA + VA (50 and 100 mg/kg orally in the 7th and 8th weeks). After the experiment was ended, the Mice were sacrificed and serum and renal tissue samples were collected for additional assessments. Treatment with VA suppressed SA-induced increase in blood urea nitrogen and creatinine in the serum. Furthermore, renal histological damage induced by SA administration was ameliorated with VA treatment. Also, the increase in the level of lipid peroxidation marker (thiobarbituric acid reactive substances) along with the reduction in total thiol levels and the diminished activities of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in the renal tissue of SA-treated mice were effectively reversed following treatment with VA. The results exhibited that the VA-treated groups (50 and 100 mg/kg) mitigated the elevation of inflammatory markers in kidney tissue (tumor necrosis factor-α and nitric oxide) in SA-exposed mice. Our research findings indicate that VA could be a potential therapeutic agent for the management of SA-associated nephrotoxicity.

Combined bisoprolol and trimetazidine ameliorate arsenic trioxide -induced acute myocardial injury in rats: targeting PI3K/GSK-3β/Nrf2/HO-1 and NF-κB/iNOS signaling pathways, inflammatory mediators and apoptosis

Background Arsenic-trioxide (ATO) is an effective therapy for acute promyelocytic leukemia. Unfortunately, its utility is hindered by the risk of myocardial injury. Both bisoprolol (BIS) and trimetazidine (TMZ) have various pharmacological features, including anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Aim The cardioprotective effects of BIS and TMZ were studied, and their mechanistic role in ameliorating ATO-induced myocardial injury. Materials and Methods Forty male Wistar rats were randomly allotted into five groups as follows: normal control group (received normal saline, orally), ATO group (7.5 mg/kg, orally), BIS (8 mg/kg, orally), TMZ (60 mg/kg, orally), and finally combination group (BIS+TMZ+ATO). Following 21 days, samples of serum and cardiac tissues were obtained to perform biochemical, molecular, and histopathological investigations. Results The present study showed that ATO caused myocardial injury evidenced by changes in serum biomarkers (Aspatate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase-MB, and cardiac troponin-1), electrolyte imbalance, and lipid profiles alongside histopathologic changes. In addition, ATO administration significantly elevated malondialdehyde, nicotinamide adenine dinucleotide phosphate hydrogen oxidase, myloperoxidase, total nitrite, inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin-1β, interleukin-6, 8-Hydroxy-2’-deoxyguanosine, nuclear factor NF-kappa-B p65 subunit, glycogen synthase kinase-3 beta, and caspase-3 expression contemporaneously with down-regulation of reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, heme oxygenase 1, nuclear factor erythroid 2–related factor 2, phosphatidylinositol-3 kinase, p-PI3K, and Bcl-2 expression. Interestingly, pretreatment with BIS and TMZ significantly reversed the detrimental effects of ATO-induced myocardial injury at both cellular and molecular levels. Otherwise, combining the two drugs displayed more enhancement than each drug alone. Conclusion The present research depicted that BIS and TMZ have the potential to protect the heart and provide therapeutic benefits by preventing acute heart injury induced by ATO. This is achieved by reversing the redox-sensitive pathway, reducing inflammation, and inhibiting apoptosis.

Fishmeal intervention after short-term novel proteins stimulates compensatory growth and affects intestinal health in largemouth bass (Micropterus salmoides).

This research utilized a compensatory growth phenomenon aimed at reducing the use of fishmeal in aquatic animal feed. However, the compensatory growth triggered by fishmeal restriction with novel protein replacement has yet to be understood. Five isonitrogenous and isolipidic diets containing different proteins were manufactured, with fishmeal serving as the control and diets containing novel proteins, i.e., Chlorella (Chlorella vulgaris), cottonseed protein concentrate, Clostridium autoethanogenum, and yellow mealworm (Tenebrio molitor), serving as the experimental diets. Largemouth bass (Micropterus salmoides) with a starting body weight of 4.73 ± 0.04g were respectively fed these five diets for the first 29days (first stage), followed by a fishmeal diet for the remaining 29days (second stage). The diet of fishmeal, Chlorella vulgaris, cottonseed protein concentrate, Clostridium autoethanogenum, and Tenebrio molitor was referred to as FM, ChM, CSM, CAP, and TM, respectively. All novel protein groups showed a 60-73% higher weight gain compared to the fishmeal group during the second phase; however, they did not reach the weight level seen in the control group. In addition, the second stage of fishmeal intervention resulted in a reduction of approximately 35% in the area of positive Alcian blue (AB) staining of intestinal tissues in the CSM group, and about 40% in the CAP group, compared to the first stage. Furthermore, the area of intestinal apoptosis in TM was enlarged after fishmeal intervention while it was decreased in other experimental groups. At day 58, gene expression analysis of the CAP group fish at the end of the trial revealed increased levels of the anti-apoptotic gene bcl-2, as well as higher expression of intestinal inflammatory cytokines il-1β, tnf-α, nf-κb p65, and il-10, compared to the FM group. In terms of the biochemical indices, the levels of catalase (CAT) and glutathione peroxidase (GSH-Px) were reduced in CSM on day 58. An assessment of potential microbial function at end of trial demonstrated that CAP could reduce the lipid metabolism and amino acid metabolism, and increased carbohydrate metabolism pathways in the largemouth bass intestine. In conclusion, both CAP and ChM groups showed promise to reduce fishmeal with respect to intestinal health rather than growth. This study should be of value to practitioners wishing to use novel proteins to reduce fishmeal via the utilization of the compensatory growth phenomenon.

DEHP impairs the oxidative stress response and disrupts trace element and mineral metabolism within the mitochondria of detoxification organs.

Di(2-ethylhexyl) phthalate (DEHP), a widely utilized plasticizer in various consumer products, is classified as an endocrine disruptor and has been implicated in numerous adverse health effects, including oxidative stress, inflammation, and metabolic disturbances. Despite the growing body of literature addressing the systemic effects of DEHP, the specific influence of DEHP-induced oxidative stress on mitochondrial function within detoxification organs, particularly the liver and kidneys, remains largely unexplored. This study evaluated the effects of DEHP exposure (0, 100, 200, and 400mg/kg/day) on mitochondrial oxidative stress, trace elements, and mineral metabolism associated with signaling pathways in the liver and kidneys of rats. Altered mitochondrial oxidative stress status was indicated by impaired glucose 6-phosphate dehydrogenase (G6PD), 6-phosphoglucerate dehydrogenase (6-PGD), glutathione reductase (GR), glutathione s-transferase (GST), and glutathione peroxidase (GPx) activities, along with significant disruptions in essential minerals and trace elements, including Na, Mg, Cu, Zn, and Fe. Key oxidative stress signaling pathways, such as NF-κB, Akt, STAT3, and CREB, glucose, and tissue homeostasis, displayed dose-dependent responses to DEHP, indicating complex regulatory mechanisms. This study represents the first comprehensive investigation into DEHP-induced mitochondrial dysfunction, highlighting its effects on oxidative stress metabolism, trace element homeostasis, and cellular signaling pathways in detoxification organs. These findings provide novel insights into the mitochondrial mechanisms underlying DEHP toxicity and underscores the need for further research into the implications of plasticizer exposure on human health.

The Protective Effects and Mechanism of Mulberry Leaf Flavonoids on Type 2 Diabetic Nephropathy Mice

Purpose: This study investigated the protective effects and mechanism of mulberry leaf flavonoids on type 2 diabetic nephropathy (DN) in mice. Methods: The DPPH free radical scavenging activity of mulberry leaf flavonoids was measured in vitro. To establish a type 2 DN model, male ICR mice were induced with streptozotocin (STZ) after a high-fat diet regimen. The mice were then divided into groups: a normal control group, a DN model group (DM), a positive control group receiving 200 mg/kg metformin (Met group), and a treatment group receiving 1 g/kg mulberry leaf flavonoids (FM group). Both Met and FM groups received daily intragastric administration for 4 weeks, while the DM and control groups were given equivalent volumes of normal saline. Fasting blood glucose levels were recorded regularly during the intervention. After the treatment period, serum creatinine (CRE), blood urea nitrogen (BUN), superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, and renal glutathione peroxidase (GPx) activity were measured. Additionally, kidney histopathological changes and glycogen deposition were evaluated by HE and PAS staining, while Nrf2 and HO-1 expression in kidney tissue was assessed through immunohistochemistry. Results: Mulberry leaf flavonoids effectively scavenged free radicals, significantly reduced blood glucose levels, CRE, BUN, and MDA in serum and kidney tissues, and increased SOD and GPx activities. Histopathological improvements in kidney and pancreatic tissues were observed, alongside increased Nrf2 and HO-1 expression. Conclusions: Mulberry leaf flavonoids ameliorate renal damage in DN mice, potentially through oxidative stress reduction and activation of the Nrf2/HO-1 signaling pathway.

Effects of Subacute Ammonia Nitrogen Stress on the Growth, Antioxidant Capability, and Immunity of Blunt Snout Bream (Megalobrama amblycephala) Juveniles

To investigate the effects of subacute ammonia nitrogen stress on the growth, antioxidant capacity, and innate immunity of juvenile blunt snout bream (Megalobrama ambrycyphala), a sample of fish (average body weight 6.55 ± 0.24 g) was divided into three groups: a control group (G1), a 10% LC50 ammonia nitrogen stress group (G2), and a 20% LC50 ammonia nitrogen stress group (G3). The fish in G1 were reared in tap water with aeration. The fish in G2 were reared in water with 6.82 mg/L ammonium chloride at 10% LC50. The fish in G3 were reared in water with 13.64 mg/L ammonium chloride at 20% LC50. The feeding period was 4 weeks. Then, the growth, antioxidant, and immune response parameters of the fish were analyzed. The results showed that the median lethal concentration (LC50) of the ammonia nitrogen solution for blunt snout bream juveniles at 96 h was 68.18 mg/L. The final body weight, weight gain, specific growth rate (SGR), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), albumin, globulin, acid phosphatase (ACP), and alkaline phosphatase (AKP) of fish in the stress groups were significantly lower than in the control group (p < 0.05); however, the MDA content of fish in the control group was significantly lower than that of those in the stress groups (p < 0.05). Furthermore, the relative expression levels of the GHRa, GHRb, IGF1, and IGF2 genes in the muscles of fish in the stress groups were significantly downregulated compared to the control group (p < 0.05). The relative expression levels of the SOD, CAT, Leap1, and Leap2 genes in the liver of fish in the stress groups were significantly lower than those in fish in the control group (p < 0.05). In conclusion, subacute ammonia nitrogen stress inhibited growth performance and decreased the antioxidant capacity and immunity of blunt snout bream.

Hepatic GPx1 and GIT1 expression altered by ethanol exposure during third trimester-equivalent development

Background Ethanol (EtOH) exposure throughout gestation and breastfeeding leads to multiple adverse outcomes in the hepatic system. Under oxidative stress, alterations in the liver are related to the inhibition of induced nitric oxide synthase activity in sinusoidal cells as a consequence of low expression of G-protein-coupled receptor (GPCR)-kinase interacting (GIT1). Here, we hypothesized that both glutathione peroxidase 1 (GPx1) and GIT1 could be altered by EtOH exposure during the third trimester of human equivalent development. Methods We exposed rats during the third trimester equivalent [postnatal days (PD) 2-8] to moderate levels of maternal EtOH (20%). GPx1 and GIT1 expression was detected by western blotting, and the antioxidant activity of glutathione peroxidase GPx and the concentration of hepatic carbonyl groups (CG were determined by spectrophotometry. Serum biochemistry parameters such as alanine aminotransferase (ALT), glucose (gluc), cholesterol (chol), and triglycerides (TG) were also measured. Results We found that ethanol decreased both GIT1 and GPx1 selenoprotein expression, affecting GPx antioxidant activity and increasing protein oxidation. Conclusions These results demonstrate for the first time that the GPx antioxidant system altered by EtOH exposure during the third trimester of development is related to a parallel decrease in GIT1 expression [1].

Conjugated fatty acids drive ferroptosis through chaperone-mediated autophagic degradation of GPX4 by targeting mitochondria

Conjugated fatty acids (CFAs) have been known for their anti-tumor activity. However, the mechanism of action remains unclear. Here, we identify CFAs as inducers of glutathione peroxidase 4 (GPX4) degradation through chaperone-mediated autophagy (CMA). CFAs, such as (10E,12Z)-octadecadienoic acid and α-eleostearic acid (ESA), induced GPX4 degradation, generation of mitochondrial reactive oxygen species (ROS) and lipid peroxides, and ultimately ferroptosis in cancer cell lines, including HT1080 and A549 cells, which were suppressed by either pharmacological blockade of CMA or genetic deletion of LAMP2A, a crucial molecule for CMA. Mitochondrial ROS were sufficient and necessary for CMA-dependent GPX4 degradation. Oral administration of an ESA-rich oil attenuated xenograft tumor growth of wild-type, but not that of LAMP2A-deficient HT1080 cells, accompanied by increased lipid peroxidation, GPX4 degradation and cell death. Our study establishes mitochondria as the key target of CFAs to trigger lipid peroxidation and GPX4 degradation, providing insight into ferroptosis-based cancer therapy.

Combined extracts of Syzygium aromaticum (Clove) and Xylopia aethiopica (Negro pepper) seeds inhibit testosterone propionate-induced benign prostatic hyperplasia in Wistar rats

Objective: Study aimed to determine the inhibition of benign prostate hyperplasia (BPH) in rats using combined extracts of Syzygium aromaticum and Xylopia aethiopica. Methods: Twenty male Wistar rats were divided into four groups:(i) normal control (NC) received normal saline (0.5 mL); (ii) testosterone propionate (TP); (iii) and (iv)testosterone propionate + 200 and 400 mg/kg b.wt of the extract. Injection was performed subcutaneously, followed by daily oral administration of the extract for 30 days. Results: Prostate weight, testosterone, prostate specific antigen (PSA), and total protein levels increased significantly (p < 0.05) in the TP only compared with those in the NC and decreased in the treatment groups. Cholesterol, TAG, and LDL-chol increased in TP relative to TP-200 and TP-400. HDL increased non-significantly (p > 0.05) across the test groups compared to TP. MDA levels increased significantly (p < 0.05) in the TP compared with those in the test groups. Catalase and glutathione peroxidase (GPx) activities decreased significantly (p < 0.05) in the TP group compared to those in the NC, TP-200, and TP-400 groups. Similarly, superoxide dismutase (SOD) increased inTP-400 compared to that in the TP and NC groups. Decreased PCV %, Hb, RBC and platelets, except WBC, were recorded in TP compared to TP-200 and TP-400. TP-200 and TP-400 presented relatively normal prostatic histomorphology compared with TP. Conclusion: The mechanisms of BPH inhibition involve the regulation of sex hormone levels and the amelioration of conditions caused by oxidative damage. Abbreviations: BPH: benign prostatic hyperplasia; CAT: catalase; DTH: dihydrotestosterone; GPx: glutathione peroxidase; HDL-Chol: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; MDA: malondialdehyde; NC: normal control; PI: prostatic interstitium; PVC: packed cell volume; PSA: prostate specific antigen; SOD: superoxide dismutase; TP: testosterone propionate; TAG: triacylglycerol

Neural Precursor Cell-Expressed Developmentally Downregulated Protein 4 (NEDD4)-Mediated Ubiquitination of Glutathione Peroxidase 4 (GPX4): A Key Pathway in High-Glucose-Induced Ferroptosis in Corpus Cavernosum Smooth Muscle Cells

Neural Precursor Cell-Expressed Developmentally Downregulated Protein 4 (NEDD4)-Mediated Ubiquitination of Glutathione Peroxidase 4 (GPX4): A Key Pathway in High-Glucose-Induced Ferroptosis in Corpus Cavernosum Smooth Muscle Cells

Oxidative stress and apoptosis of the spinal cord in a rat model of retinoic acid-induced neural tube defects.

Neural tube defects (NTDs) are severe congenital anomalies that significantly impact the central nervous system, arising from the neural tube's failure to close during early embryogenesis. In this study, we investigated NTDs and associated pathophysiological mechanisms in foetal rats following exposure to all-trans retinoic acid (atRA). Out of 168 embryos from 15 pregnant rats in the experimental group, 78% displayed NTDs with notable spinal deformities, primarily in the lumbar-sacral region, similar to human cases. Body weight and crown-rump length (CRL) measurements indicated significant growth impairment in the NTD group compared to controls, while the atRA-treated group without NTDs showed no notable differences in growth. Immunohistochemistry (IHC) results demonstrated decreased NeuN and PCNA expression in the NTD group's spinal cord. Oxidative stress markers showed markedly reduced superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity, alongside increased malondialdehyde (MDA) levels in the NTD group, indicating heightened oxidative stress. Analysis of apoptosis-related proteins revealed elevated Bax and caspase-3 levels, reduced Bcl-2 and lower poly (ADP-ribose) polymerase (PARP) in the NTD group, suggesting a pronounced shift towards proapoptotic pathways, potentially contributing to NTD progression. Our findings indicate that oxidative stress and apoptosis play significant roles in the development of NTDs. Future investigations should aim to pinpoint critical regulatory genes or proteins that might be targeted for therapeutic interventions to alleviate oxidative stress and apoptosis in NTD development.

Antiplasmodial Potentials, Phytocompounds and the Possible Toxic Effects of Administration of Ethylacetate Extract of Spondias mombin Linn.

Malaria, caused by Plasmodium parasites, is a global health concern. Natural products, such as plant extracts, are investigated for new antimalarial agents. Spondias mombin, traditionally used for medicinal purposes, was examined for its effects on parasitemia, haematological parameters, antioxidant activities, liver function biomarkers, and serum electrolytes in Plasmodium berghei-infected mice. Mice received varying doses of the ethylacetate extract. Various dosages of the extract and the prescribed medication dramatically slowed the parasite's growth. The extract significantly improved red blood cell (RBC) and platelet counts, particularly at higher doses. Hemoglobin levels were decreased dose-dependently. Antioxidant analysis showed increased superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced catalase (CAT) activities and malondialdehyde (MDA) levels, indicating robust antioxidant properties. Liver function tests showed mixed effects, with elevated AST, ALP, and TB levels at some doses, yet decreased ALT at the highest dose, suggesting possible hepatoprotective effects. Serum electrolyte levels remained stable. Seventy-eight (78) bioactive components were identified in the extract by GC-MS analysis. The extract demonstrated substantial antimalarial and antioxidant capacities, with minimal liver stress and stable electrolyte levels, suggesting safety as an adjunct therapy for malaria. Further research is needed to ascertain the specific antimalarial bioactive constituents and their mechanisms of action.

Dietary antioxidant capacity is inversely associated with F2- isoprostane and body fat percentage in elite soccer referees

Background Dietary antioxidant Capacity (DaC) has been used as a tool for predicting plasma and dietary antioxidant concentrations. However, the DaC association with oxidative stress (OS) and body composition parameters is an unexplored area, mainly in physically active individuals. Given the potential for increased OS in physically active individuals, it becomes crucial to investigate this association. The aim of this study was to analyze the association between DaC, OS biomarkers, and body composition in healthy and physically active individuals. Methods This Cross-sectional study included 20 male soccer referees. Body composition measurements (body mass, fat mass, lean mass, and waist circumference), OS biomarkers (F2-isoprostane, total antioxidant state, total oxidative status, reduced glutathione, oxidized glutathione, superoxide dismutase, glutathione peroxidase (GPx) and catalase), and DaC were evaluated. Linear regression models were used to determine the association between DaC and the dependent variables. The study was approved by the Human Research Ethics Committee of the Federal University of Santa Catarina (UFSC), CAAE 82584318.0.0000.0121, and file no. 2.572.301. Results DaC was inversely associated with F2-isoprostane (p = 0.044), GPx activity (p = 0.048), and body fat percentage (p = 0.025). Conclusions Increased DaC in physically active individuals may bring benefits related to biomarkers of OS, such as decreasing F2-isoprostane and increasing GPx activity. The increase in DaC also showed an improvement in body composition, demonstrated by the lower percentage of body fat in the study subjects.

DNMT aberration-incurred GPX4 suppression prompts osteoblast ferroptosis and osteoporosis

Osteoporosis (OP) is a common and fracture-prone skeletal disease characterized by deteriorated trabecular microstructure and pathologically involving various forms of regulated bone cell death. However, the exact role, cellular nature and regulatory mechanisms of ferroptosis in OP are not fully understood. Here, we reported that OP femurs from ovariectomized (Ovx) mice exhibited pronounced iron deposition, ferroptosis, and transcriptional suppression of a key anti-ferroptotic factor GPX4 (glutathione peroxidase 4). GPX4 suppression was accompanied by hypermethylation of the Gpx4 promoter and an increase in DNA methyltransferases DNMT1/3a/3b and was transcriptionally promoted by repressive KLF5 and the transcriptional corepressors NCoR and SnoN. Conversely, DNMT inhibition with SGI-1027 reversed promoter hypermethylation, GPX4 suppression and ferroptotic osteoporosis. In cultured primary bone cells, ferric ammonium citrate (FAC) mimicking iron loading similarly induced GPX4 suppression and ferroptosis in osteoblasts but not in osteoclasts, which were rescued by siRNA-mediated individual knockdown of DNMT 1/3a/3b. Intriguingly, SGI-1027 alleviated the ferroptotic changes caused by FAC, but not by a GPX4 inactivator RSL3. More importantly, we generated a strain of osteoblast-specific Gpx4 haplo-deficient mice Gpx4Ob+/− that developed spontaneous and more severe ferroptotic OP alterations after Ovx operation, and showed that GPX4 inactivation by RSL3 or semi-knockout in osteoblasts largely abolished the anti-ferroptotic and osteoprotective effects of SGI-1027. Taken together, our data suggest that GPX4 epigenetic suppression caused by DNMT aberration and the resulting osteoblastic ferroptosis contribute significantly to OP pathogenesis, and that the strategies preserving GPX4 by DNMT intervention are potentially effective to treat OP and related bone disorders.

EVALUATION OF GLUTATHIONE PEROXIDASE ACTIVITY, MALONYLALDEHYDE AND SELENIUM LEVELS IN SICKLE CELL ANAEMIA INDIVIDUALS ATTENDING NAUTH, NNEWI IN SOUTH-EASTERN NIGERIA.

Background: Oxidative stress is an imbalance between the production and clearance of toxic free radicals known as reactive oxygen species (ROS). It is associated with hemolysis, a hallmark of SCD. SCD has long been recognized as an inflammatory condition and oxidative stress play important role in pathophysiology of SCA. Imbalance between production and elimination of reactive oxygen species (ROS) damages cell structures, including lipids, membranes, proteins and nucleic acids resulting in cell death or altered cell function. Aim: The aim of this study was to measure the serum level of Glutathione peroxidase, Malonaldehyde and Selenium in SCA (HbSS) in their steady state, AA (Healthy adult) and AS (sickle cell carriers) Methods: This is a cross- sectional study. A total of one hundred and fifty aged matched participants were recruited for this study.50 SCA subjects with sickle cell anemia (SS). Glutathione peroxidase and Malonyaldehyde were measured using turbidometry and colorimetric methods respectively while Selenium was analysed using Atomic Absorption Spectrophotometry (AAS) Results: The result of analysis of variance (ANOVA) showed that the mean serum level of MDA concentration (2.97±0.29) was higher in the SS group and was statistically significant (p&lt; 0.05). MDA concentration was lower in the AS group. In the post hoc analysis MDA was statistically significant between SS vs AS and AA vs AA. The glutathione peroxidase activity was significantly lower in the SS group (0.85±0.12) compare with the mean values obtained in the AA and AS group. The GPx activity among the three groups was statistically significant while the post hoc analysis among the three groups showed statistical difference and was significant (p &lt; 0.005) The Selenium levels in the SS group is lower compared with the values observed between the AA and AS group. The Se levels in the SS group was statistically lower (5.73±1.34) (p &lt; 0.05) and showed significant difference. The comparison study between AS vs SS and AA vs AA were statistically significant. Conclusion: The decrease in selenium level potentiates low and weakened antioxidant activity and capacity which also is a reflection of low level of glutathione peroxidase observed which is supposed to attack free radicals to prevent oxidative stress. The findings from this study are in tandem with other researches suggesting that the pathophysiology of sickle cell disease is associated with oxidative stress

Immunotherapeutic and Cell-Protective Effects of Probiotic Kefir on Cyclophosphamide‐induced Nephrotoxicity and Urotoxicity in Rats

To evaluate kefir, a naturally occurring fermented dairy product, with pharmacological and therapeutic qualities including antioxidant, anti-apoptotic, and anti-inflammatory effects against cyclophosphamide (CP)-induced hemorrhagic cystitis and nephrotoxicity in rats. For this purpose, experimental rats were divided into 6 groups; control (Group 1), 150 mg/kg CP (Group 2), 5 mg/kg kefir (Group 3), l0 mg/kg kefir (Group 4), 5 mg/kg kefir+150 CP (Group 5), l0 mg/kg kefir+150 CP (Group 6). Since there was no difference in kefirs fermented on different days, kefirs from the 1st, 2nd, and 3rd days were mixed and given to the rats for 12 days, while CP was given as an only dose and i.p. on the 12th day of the experiment. Histologic evaluations revealed that CP caused toxicity in kidney and bladder. On the other hand, biochemical evaluations showed a significant increase in serum blood urea nitrogen (BUN) and creatinine (Cre) levels, which are tissue toxicity markers, and a significant decrease in catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, which are intracellular antioxidant system markers, in the CP-treated experimental group. However, all values were reversed as a result of kefir (5 and 10 mg/kg) treatment. These results showed that kefir is an effective protective agent against CP-induced hemorrhagic cystitis and nephrotoxicity.

Molecular insights into the physiological impact of low-frequency noise on sea slug Onchidium reevesii: Activation of p53 signaling and oxidative stress response

To investigate the regulatory role of tumor protein p53 of sea slug (Onchidium reevesii) under oxidative stress conditions, we examined the response mechanisms of O. reevesii to low-frequency noise pollution (1000 Hz) using molecular and cellular biology techniques. We successfully cloned the O. reevesii p53 gene (Orp53) from O. reevesii, obtaining a 3356 bp sequence containing a 2727 bp open reading frame (ORF). Phylogenetic analysis revealed that O. reevesii shares a close evolutionary relationship with other molluscs, including Bulinus truncatus and Elysia marginata. Expression analysis showed that Orp53 is expressed across various tissues, with the highest expression levels in the hepatopancreas. Using RNA interference (RNAi) to silence the Orp53 gene, we found that the mRNA expressions of Orp53 and its downstream apoptosis-related genes, including cytochrome C (Cyt_C), Caspase 9, and Caspase 3, were significantly suppressed until the third day of interference (P < 0.05). Moreover, sip53 treatment resulted in significant reductions in the mRNA expression and protein levels of all studied genes (P < 0.05) compared to the noise-exposed group. In addition, the low-frequency noise exposure decreased central nervous system (CNS) viability while increasing oxidative stress markers, including reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione S-transferase (GST). On the other hand, silencing Orp53 expression via siRNA resulted in significant reductions in CNS cell viability (P < 0.05). Our study establishes a molecular basis for evaluating the consequences of marine noise pollution, confirming that low-frequency noise activates the p53 signaling pathway, oxidative stress, and that p53 can regulate oxidative stress and apoptosis-related genes.

Longikaurin A induces ferroptosis and inhibits glioblastoma progression through DNA methylation - Mediated GPX4 suppression.

Glioblastoma (GBM) is the most common primary intracranial tumor highly resistant to conventional clinical chemotherapy. Recently, the induction of ferroptosis is emerging as a putative strategy to treat various tumors. However, the identification of the effective and applicable tumor ferroptosis-inducing agents remains challenging. In this study, we showed that longikaurin A (LK-A), a natural diterpenoid isolated from the medicinal plant Isodon ternifolius with strong anti-GBM capacities, induced remarkable GBM cell ferroptosis along with suppressing the key anti-ferroptosis factor glutathione peroxidase 4 (GPX4). GPX4 promoter contains conserved CpG islands. The LK-A-induced GPX4 suppression coincided with the inhibition of ten-eleven translocation 2 (TET2), a key DNA demethylation enzyme and an increase in the hypermethylation of the GPX4 promoter. Further, LK-A promoted the GBM ferroptotic alterations and inhibited GBM progression in both subcutaneous and orthotopic xenograft mouse models, whereas GPX4 overexpression largely abrogated its anti-GBM effects both in vitro and in vivo, suggesting that LK-A inductions of the DNA methylation-incurred GPX4 suppression and ferroptosis are crucial for its anti-GBM functions. Together, our study has elaborated an important epigenetic pathway of GBM ferroptosis and uncovered a critical pharmacological property of LK-A for treating GBM patients.

Induction of GPX4-regulated ferroptotic stress promotes epithelial-to-mesenchymal transition in renal tubule cells induced by PM2.5

Increasing evidence links exposure to fine particulate matter (PM2.5) with an elevated risk of kidney disease. In this study, we investigated the effect of PM2.5 exposure on human proximal tubular epithelial (HK−2) cells and found that it elevated ferroptotic stress markers, including increased iron, reactive oxygen species (ROS), and malondialdehyde (MDA), along with reducing glutathione (GSH) levels. PM2.5 promotes the epithelial-to-mesenchymal transition (EMT) in these cells, which is associated with the loss of epithelial morphology, lowered expression of E-cadherin, and elevated expression of α-smooth muscle actin (α-SMA). Notably, a reduction in PM2.5-induced EMT characteristics was observed using either a ferroptosis-specific inhibitor (Fer-1) or a mitochondrial ROS scavenger (Mito-Tempo). Moreover, Fer-1 effectively counteracted ferroptotic stress and restored glutathione peroxidase 4 (GPX4) expression in PM2.5-exposed cells, which may explain its efficacy in inhibiting EMT induced by PM2.5. In contrast, GPX4 knockdown exacerbated EMT features in PM2.5-treated cells. Further studies showed that GPX4 overexpression alleviated EMT markers in mouse tubular cells following PM2.5 exposure, indicating the role of GPX4 in reducing ferroptotic stress and may prevent tubular injury caused by PM2.5 exposure. Our study highlights that PM2.5 may induce GPX4-regulated ferroptotic stress in tubular cells, potentially triggering the EMT process and contributing to kidney injury.