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Radiation-induced brain injury (RBI) presents a significant challenge for patients undergoing radiation therapy for head, neck, and intracranial tumors. This review aims to elucidate the role of ferroptosis in RBI and its therapeutic implications. Specifically, we explore how ferroptosis can enhance the sensitivity of tumor cells to radiation while also examining strategies to mitigate radiation-induced damage to normal brain tissues. By investigating the mechanisms through which radiation increases cellular reactive oxygen species (ROS) and initiates ferroptosis, we aim to develop targeted therapeutic strategies that maximize treatment efficacy and minimize neurotoxicity. The review highlights key regulatory factors in the ferroptosis pathway, including glutathione peroxidase 4 (GPX4), cystine/glutamate antiporter system Xc- (System Xc-), nuclear factor erythroid 2-related factor 2 (NRF2), Acyl-CoA synthetase long-chain family member 4 (ACSL4), and others, and their interactions in the context of RBI. Furthermore, we discuss the clinical implications of modulating ferroptosis in radiation therapy, emphasizing the potential for selective induction of ferroptosis in tumor cells and inhibition in healthy cells. The development of advanced diagnostic tools and therapeutic strategies targeting ferroptosis offers a promising avenue for enhancing the safety and efficacy of radiation therapy, underscoring the need for further research in this burgeoning field. [ABSTRACT FROM AUTHOR]

In this study, we used computational design and protein engineering to modify stabilizing protein 1 to mimic glutathione peroxidase (GPx), and constructed a reversible protein-assembled nanoscale artificial selenidase based on Ni2+-response. Its unique glutathione substrate recognition site and spatial orientation of the Se active center endow it with high GPx activity. The experimental results showed that the spatial barrier formed by Ni2+-induced assembly can inhibit enzyme activity, and EDTA can dissociate and restore activity. And the reversible protein assembly system is robust after multiple cycles, demonstrating the potential of this "intelligent" artificial selenoenzymatic nanomaterials for controllable catalytic applications in biomedicine. [ABSTRACT FROM AUTHOR]

Background: Potentilla fulgens Wall. ex Sims. is a medicinal plant used by the locals of Meghalaya. However, its mechanism of action has not been well elucidated. Hence, this study investigated the effect of P. fulgens on IRS1 and Akt. The interaction of the various polyphenols present in P. fulgens with the IR tyrosine kinase and IRS1 PTB domain was studied using auto dock. Changes in expression of antioxidant enzymes, IRS-1, Akt and behavior of normal, diabetic, and diabetic mice treated mice were assessed after 14 days of treatment. Morphological changes in the liver tissue were determined by Transmission Electron Microscopy. Results: The effect of P. fulgens on blood glucose was time and dose dependent. Treatment with P. fulgens, Cat, E, CE, CEP and metformin improved the activity of catalase, glutathione peroxidase, glycogen, IRS-1 and Akt. The Forced Swimming test showed an altered behavior in diabetic mice. The altered mobility was reverted back to near normal on treatment with P.fulgens, Cat, E, CE, CEP and metformin. The morphological aberrations seen in diabetic animals considerably improved in the treated diabetic group. Conclusion: P. fulgens and its phytochemicals-catechin and epicatechin are potent sources of antidiabetic drugs, possibly mediating their effects through upregulation of insulin IRS-1 and Akt. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Rhamnolipids (RLS) are surfactants that improve the growth performance of poultry by improving the absorption of nutrients. This study aims to investigate the effects of RLS replacement of chlortetracycline (CTC) on growth performance, slaughtering traits, meat quality, antioxidant function and nuclear‐factor‐E2‐related factor 2 (Nrf2) signaling pathway in broilers. A total of 600 one‐day‐old Arbor Acres chicks were randomly assigned to five groups with eight replicates in each group, raised for 42 days. Broilers were respectively fed a basal diet with no CTC or RLS, 75 mg kg−1 CTC, and 250, 500, 1000 mg kg−1 RLS.Dietary supplementation with RLS linearly increased the average daily gain, average daily feed intake, carcass yield, eviscerated yield, ether extract, enhanced total superoxide and glutathione peroxidase (GPx) activities, overexpressed the relative expressions of Nrf2, heme oxygenase 1, Copper/zinc superoxide dismutase, Manganese superoxide dismutase, GPx and catalase and decreased the lightness value at 24 h, drip loss and malondialdehyde contents of broilers (P < 0.05). Compared with the control group, broilers fed 1000 mg kg−1 RLS reduced the drip loss and broilers fed 500 mg kg−1 RLS increased muscle crude fat content (P < 0.05). Compared with the CTC group, dietary supplementation with 1000 mg kg−1 RLS increased eviscerated yield (P < 0.05).RLS could improve growth performance, crude fat content, meat quality and antioxidant capacity and activate relative expression of genes in the Nrf2 signaling pathway in broilers. It could be used as an antibiotic substitute in diets and the recommended supplemental dose of RLS in feed of broilers is 1000 mg kg−1. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

1. This study evaluated the effects and mechanisms of action of the peptide gADP3 on hepatic inflammatory injury induced by lipopolysaccharide (LPS).2. Hepatic inflammatory injury was induced in geese by intraperitoneal injection of LPS and gADP3, and the adiponectin receptor agonist AdipoRon (positive control) was used for potential amelioration. Serum inflammatory factor levels, liver function-related biochemical indicators and oxidative stress-related biochemical parameters in the liver tissues were determined. The expression levels of adiponectin and its receptors, inflammation and oxidative stress-related genes and key signalling molecules involved in adiponectin, inflammation and oxidative stress signalling pathways in liver tissues were detected.3. The peptide gADP3 alleviated inflammatory cell infiltration and hepatic inflammatory changes, reversed the decrease in serum albumin (ALB), total protein (TP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) content or activity induced by LPS and increased the activity of the antioxidant enzymes CAT (catalase), SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase).4. The peptide gADP3 upregulated the expression of antioxidant enzyme-related genes GCLC, HO-1 and NQO1 in liver tissues, decreased the levels of inflammatory factors like TNF-α, IL-1β, IL-6, IFN-γ and TGF-β and reduced mRNA expression levels of inflammatory-related genes TNF-α, IL-1β, iNOS and TGF-β. Additionally, it increased the mRNA and protein expression levels of adiponectin and its receptors, as well as key molecules in the adiponectin signalling pathway like AMPK and PPARα. In addition, gADP3 reversed the changes in mRNA or protein expression of inflammatory and oxidative stress signalling pathway-related genes P38MAPK, NF-κBP65, TLR4 and Nrf2 in liver tissues caused by LPS treatment.5. In conclusion, goose-derived adiponectin peptide gADP3, similar to the adiponectin receptor agonist AdipoRon, attenuated LPS-induced hepatic inflammatory injury in geese. [ABSTRACT FROM AUTHOR]

Epilepsy, characterized by recurrent seizures, poses a significant health challenge globally. Despite the availability of anti-seizure medications, their adverse effects and inadequate efficacy in controlling seizures propel the exploration of alternative therapeutic measures. In hypothesis, glycitin is a phytoestrogenic compound found in soybeans and due to its estrogenic properties may have anti-epileptic and neuroprotective effects. This study investigates the potential anti-epileptic properties of glycitin in the context of pentylenetetrazol (PTZ) induced seizures in male Wistar rats. The rats were pretreated with varying doses of glycitin (5, 10, and 20 mg/kg) before PTZ (35 mg/kg) administration, and assessments included behavioral observations and histological evaluation via hematoxylin and eosin (H&E) staining. Additionally, oxidative stress markers, such as malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels, were quantified to examine glycitin's impact on oxidative stress. Molecular analysis was conducted to assess the activation of the Nuclear factor erythroid 2-related factor (Nrf2)/Heme oxygenase 1 (HO-1) signaling pathway. Results indicated that glycitin pretreatment effectively mitigated PTZ-induced convulsive behaviors, supported by histological findings from H&E staining. Furthermore, glycitin administration led to significant alterations in MDA, GPx, and SOD levels, suggestive of its ability to modulate oxidative stress. Notably, glycitin treatment induced activation of the Nrf2/HO-1 signaling pathway. These findings underscore the potential of glycitin as an anticonvulsant agent, elucidating its mechanism of action through histological protection, modulation of oxidative stress markers, and activation of the Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Konzo is a neglected paralytic neurological disease associated with food (cassava) poisoning that affects the world's poorest children and women of childbearing ages across regions of sub-Saharan Africa. Despite understanding the dietary factors that lead to konzo, the molecular markers and mechanisms that trigger this disease remain unknown. To identify potential protein biomarkers associated with a disease status, plasma was collected from two independent Congolese cohorts, a discovery cohort (n = 60) and validation cohort (n = 204), sampled 10 years apart and subjected to multiple high-throughput assays. We identified that Glutathione Peroxidase 3 (GPx3), a critical plasma-based antioxidant enzyme, was the sole protein examined that was both significantly and differentially abundant between affected and non-affected participants in both cohorts, with large reductions observed in those affected with konzo. Our findings raise the notion that reductions in key antioxidant mechanisms may be the biological risk factor for the development of konzo, particularly those mediated through pathways involving the glutathione peroxidase family. The search for biomarkers associated with konzo disease has been a long-standing question within the research community. Here, the authors have uncovered a potential biomarker for konzo that is associated with the ability to manage oxidative damage. [ABSTRACT FROM AUTHOR]

The impact of Sodium Houttuyniae (SH) on lipopolysaccharide (LPS)-induced ALI has been investigated extensively. However, it remains ambiguous whether ferroptosis participates in this process. This study aimed to find out the impacts and probable mechanisms of SH on LPS-induced ferroptosis. A rat ALI model and type II alveolar epithelial (ATII) cell injury model were treated with LPS. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (HE) staining, and Giemsa staining were executed to ascertain the effects of SH on LPS-induced ALI. Moreover, Transmission electron microscopy, Cell Counting Kit-8 (CCK8), ferrous iron colorimetric assay kit, Immunohistochemistry, Immunofluorescence, Reactive oxygen species assay kit, western blotting (Wb), and qRT-PCR examined the impacts of SH on LPS-induced ferroptosis and ferroptosis-related pathways. Theresults found that by using SH treatment, there was a remarkable attenuation of ALI by suppressing LPS-induced ferroptosis. Ferroptosis was demonstrated by a decline in the levels of glutathione peroxidase 4 (GPX4), FTH1, and glutathione (GSH) and a surge in the accumulation of malondialdehyde (MDA), reactive oxygen species (ROS), NOX1, NCOA4, and Fe2+, and disruption of mitochondrial structure, which were reversed by SH treatment. SH suppressed ferroptosis by regulating TRAF6-c-Myc in ALI rats and rat ATII cells. The results suggested that SH treatment attenuated LPS-induced ALI by repressing ferroptosis, and the mode of action can be linked to regulating the TRAF6-c-Myc signaling pathway in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to be renoprotective in ischemia-reperfusion (I/R) injury, with several proposed mechanisms, though additional mechanisms likely exist. This study investigated the impact of luseogliflozin on kidney fibrosis at 48 h and 1 week post I/R injury in C57BL/6 mice. Luseogliflozin attenuated kidney dysfunction and the acute tubular necrosis score on day 2 post I/R injury, and subsequent fibrosis at 1 week, as determined by Sirius red staining. Metabolomics enrichment analysis of I/R-injured kidneys revealed suppression of the glycolytic system and activation of mitochondrial function under treatment with luseogliflozin. Western blotting showed increased nutrient deprivation signaling with elevated phosphorylated AMP-activated protein kinase and Sirtuin-3 in luseogliflozin-treated kidneys. Luseogliflozin-treated kidneys displayed increased protein levels of carnitine palmitoyl transferase 1α and decreased triglyceride deposition, as determined by oil red O staining, suggesting activated fatty acid oxidation. Luseogliflozin prevented the I/R injury-induced reduction in nuclear factor erythroid 2-related factor 2 activity. Western blotting revealed increased glutathione peroxidase 4 and decreased transferrin receptor protein 1 expression. Immunostaining showed reduced 4-hydroxynonenal and malondialdehyde levels, especially in renal tubules, indicating suppressed ferroptosis. Luseogliflozin may protect the kidney from I/R injury by inhibiting ferroptosis through oxidative stress reduction. [ABSTRACT FROM AUTHOR]

Among developed countries, breast carcinoma is one of the most common cancers in women. Breast carcinoma is the result of the fusion of several biological structures, each with its own physiological characteristics and clinical repercussions. The Ficus genus has been reported to have important pharmacological properties in a variety of plants. The current study examined at the anti-mammary action of Ficus glomerata leaf column elute (FGLCE) in 12-Dimethylbenz (α) anthracene (DMBA) driven breast cancer and the mechanism behind it. To produce tumors in female rats, a single dosage of DMBA (25 mg/kg) was injected into the mammary gland. The female rats were divided into five groups- Group I. Control group; Group II- control + FGLCE (100mg/kg of BW); Group III- DMBA treated rats; Group IV- DMBA + FGLCE treated; Group V- DMBA + DOX (5 mg/kg) treated rats. Tumor burden, incidence, and volume were measured at the end of the experiment.The lipid profile (TC, FFA, PL, and TG) in plasma, liver tissue, and mammary tissue were all calculated.At a dose of 25 mg/kg body weight, DMBA inhibits the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPX).DMBA at a dose concentration 25mg/ kg body weight xenobiotic markers increased in group III rats When compared to the control group and glycoprotein p53, and TNF-α, the dosedependent treatment with FGLCE (P<0.05) significantly reduced .Hepatic markers such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), tumor necrosis factor- (TNF-α), and inflammatory mediators such as nuclear factor kappa-B(NF-kB) were considerably (P<0.05) down regulated by FGLCE. FGLCE significantly (P<0.05) reduced apoptotic regulator (Bax), B-cell lymphoma 2 (Bcl-2), and Breast Cancer gene 1 (BRCA-1) expression when compared to DMBA control group rats.Therefore, the findings suggest that FGLCE has a protective effect against DMBA-induced mammary gland in rats. [ABSTRACT FROM AUTHOR]

The present study was conducted on a group of women with breast cancer (60 women) and a group of healthy women as a control group (30 women) aged (27-85) years. Samples were collected from women with breast cancer from the Teaching Oncology Hospital - Medical City, Baghdad for the period from the first of October 2023 until the end of February 2024. The activity of servivin was asses and the level of glutathione, glutathione peroxidase, malondialdehyde and the following results were obtained: 1-There was a significant increase in the group of breast cancer women for both servivin, and malondialdehyde compared to the control group. 2- There was a significant decrease in the level of glutathione-and glutathione peroxidase . 3-The existence of a significant correlation between survivin and each of GSH and GPX. Conclusions: The results of the present study showed a significant increase in the level of survivin in women with breast cancer in conjunction with a significant correlation with GSH, GPX, MDA and BMI, which supports the possibility of considering survivin as an indicator for breast cancer diagnosis. [ABSTRACT FROM AUTHOR]

Aim. To investigate and assess the concentrations of glutathione peroxidase, superoxide dismutase, catalase, vitamin A and vitamin C in Iraqi patients infected by chronic myeloid leukemia (CML). Material and methods. Forty-eight Iraqi patients of ages ranged between (15-75) years took part in the current study. Enzymatic antioxidants (Gpx, SOD and CAT) and antioxidant vitamins (A and C) were estimated spectrophotometrically in blood sera of all patients according to age and sex variables, and then all clinical parameters were compared with healthy individuals (control groups). Results. Evaluation of oxidant-antioxidant status. Glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) enzymes concentrations recorded high significant decreasing (***p <0.0001) in blood serum of CML patients according to age and sex factors. Moreover, vitamins A and C showed a high significant decreasing (***p <0.0001) in their concentrations as measured in blood serum of CML patients with diverse ages and sexes. The GPx, SOD, CAT, Vitamin A and Vitamin C in the current study, are considered excellent biochemical markers for following the acuity of CML disease depending on age and sex variables. Conclusion. The clinical significance of oxidative stress represented by lack of enzymes and vitamins in the current study was proven. Statistically significant differences were recorded and observed between patients and control groups depending on age and sex factors. [ABSTRACT FROM AUTHOR]

Euglena gracilis , a fascinating organism in the scientific realm, exhibits characteristics of both animals and plants. It maintains redox homeostasis through a variety of enzymatic and non-enzymatic antioxidant molecules. In contrast to mammals, Euglena possesses nonselenocysteine glutathione peroxidase homologues that regulate its intracellular pools of reactive oxygen species. In the present study, a full-length cDNA of chloroplastic EgGPXL-1 was isolated and subjected to biochemical and functional characterization. Recombinant EgGPXL-1 scavenged H2O2 and t -BOOH, utilizing thioredoxin as an electron donor rather than glutathione. Despite its monomeric nature, EgGPXL-1 exhibits allosteric behavior with H2O2 as the electron acceptor and follows typical Michaelis–Menten kinetics with t -BOOH. Suppression of EgGPXL-1 gene expression under normal and high-light conditions did not induce critical situations in E. gracilis , suggesting the involvement of compensatory mechanisms in restoring normal conditions. [ABSTRACT FROM AUTHOR]

Organic selenium is a major antioxidant that can protect against oxidative stresses by stimulating the antioxidant cascades. We have evaluated the capacity of dietary selenium-enriched yeast (Se-Y) to alleviate thermal stress in juvenile Penaeus vannamei shrimp. The Se-Y level in the control group (Cont) was 0 mg Se kg−1 ration and 0.4 mg Se kg−1 in the AlkoSel and SelPlex groups (commercial Se-Y products). The shrimp were initially provided the three experimental diets while being maintained in their thermal comfort zone (28 °C) for 30 days, following which time the temperature was increased up to 33 °C for 1 and 6 h of induced heat stress challenge (IHSC). Variations in the levels of malondialdehyde (MDA), glutathione, and several transcriptional factors encoding antioxidant variables and stress-responsive proteins were analyzed in the gill, muscle, and hepatopancreas. The results revealed that the MDA and glutathione content of the shrimp were significantly impacted by Se-Y supplementation both before and after the IHSC. Prior to the IHSC, in all evaluated tissues, Se-Y supplementation enhanced the antioxidant variables (glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase) and heat shock protein (HSP) biosensors HSP70 and HSP90 while depressing the immune stress-related indices (gamma-interferon inducible lysosomal thiol reductase-like and aspartate aminotransferase cytoplasmic-like (AST). After IHSC, in all evaluated tissues, the AST gene was significantly downregulated in all Se-Y-fed groups while the other genes were upregulated. These results imply an important role of organic selenium in preventing organ dysfunctions after exposure to IHSC. Taken together, these findings on gene regulation after Se-Y pretreatment will be useful for monitoring organ dysfunction and preparing therapeutic agents for thermal endurance in P. vannamei. [ABSTRACT FROM AUTHOR]

Neuropathic pain (NP) significantly impacts the quality of life due to its prolonged duration and lack of effective treatment. Recent findings suggest that targeting neuroinflammation is a promising approach for treating NP. G protein‐coupled receptor 55 (GPR55), a member of the GPCR family, plays an important role in neuroinflammatory regulation. CID16020046, a GPR55 agonist, possesses promising anti‐neuroinflammatory effects. Herein, the therapeutic effect of CID16020046 on NP was investigated in an NP rat model. The NP model was established using the unilateral sciatic nerve chronic constriction injury (CCI) assay. Both sham and CCI rats were intraperitoneally administered with 20 mg/kg CID16020046. NP was assessed using paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). First, we showed that GPR55 was downregulated in the spinal dorsal horn of CCI rats. After CCI rats were treated with CID16020046, the values of PWT and PWL were increased, indicating their effect on pain relief. The treated rats had attenuated release of inflammatory cytokines in the spinal cord, decreased spinal malondialdehyde (MDA) levels, and increased spinal glutathione peroxidase (GSH‐PX) activity. Additionally, the increased levels of phosphorylated nuclear factor (NF)‐κB p65 in CCI rats were significantly alleviated by CID16020046 treatment. Mechanistically, we showed that CID16020046 significantly suppressed the activation of the Janus kinase (JAK2)/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in the spinal cord of CCI‐treated rats. However, Colivelin TFA (a STAT3 agonist) abolished the effect of CID16020046 on JAK2/STAT3 activation. In conclusion, our data demonstrate that the activation of GPR55 by CID16020046 alleviates NP and neuroinflammation in CCI rats by mediating the JAK2/STAT3 pathway. [ABSTRACT FROM AUTHOR]

Innovative solutions for rapid protection against broad-spectrum infections are very important in dealing with complex infection environments. We utilized a functionally inactive mutated endolysin protein of Streptococcus pneumoniae (ΔA146Ply) to immunize mice against pneumonic infections by multidrug-resistant bacteria, Candida albicans and influenza virus type A. ΔA146Ply protection relied on both immunized tissue-resident and monocyte-derived alveolar macrophages and inhibited infection induced ferroptosis that upregulated expression of GPX4 (glutathione peroxidase) in alveolar macrophages. Ferroptosis resistance endowed macrophages with enhanced phagocytosis by inhibiting lipid peroxidation during infection. Moreover, we demonstrated ΔA146Ply upregulated GPX4 through the TLR4/IRG1/NRF2 pathway. ΔA146Ply also induced ferroptosis inhibition and phagocytosis improvement in human monocytes. This mode of action is a novel and potentially prophylactic and rapid broad-spectrum anti-infection mechanism. Our study provides new insights into protective interventions that act by regulating ferroptosis to improve multiple pathogen resistance via GPX4 targeting. [Display omitted] • ΔA146Ply is a novel prophylactic and broad-spectrum mucosal anti-infective strategy. • GPX4 by ΔA146Ply inhibits ferroptosis and augments phagocytosis in macrophages. • ΔA146Ply upregulates GPX4 through the TLR4/IRG1/NRF2 pathway. • ΔA146Ply inhibits ferroptosis and improves phagocytosis in human monocytes. • New insights into prophylactic anti-infectious prospect by targeting GPX4. [ABSTRACT FROM AUTHOR]

Summary: Betaine is a natural antioxidant lacking the ability to scavenge free radicals. Although it has been shown to exert antioxidant function by enhancing the expression of antioxidant enzymes, its mechanism has not yet been elucidated. This study explored the role and mechanism of the transcription factor NF‐E2‐associated factor 2 (Nrf2)‐Kelch‐like epichlorohydrin‐associated Protein 1 (Keap1) antioxidant reaction element (ARE) pathway in betaine‐mediated enhancement of antioxidant enzyme expression. Results derived from real‐time quantitative PCR, Western blot, quantitative methylation‐specific PCR, and inhibitors assay experiments showed that betaine activated the Nrf2‐Keap1‐ARE pathway, leading to an increase in the mRNA level of superoxide dismutase, glutathione peroxidase, and heme oxygenase‐1. The mechanism may involve betaine's promotion of DNA methyltransferase expression, resulting in increased methylation of Keap1 DNA promoter, which ultimately reduces the level of Keap1 mRNA. Therefore, betaine can directly activate the Nrf2‐Keap1‐ARE pathway by increasing the methylation level of Keap1 DNA promoter, thereby improving the expression of antioxidant enzymes. This study will contribute to unveiling a new antioxidant mechanism for betaine. [ABSTRACT FROM AUTHOR]

This literature review emphasizes the innovative role of ferroptosis in cancer treatment. Ferroptosis is a kind of deliberate cell death that is characterized by the generation of lipid peroxides and needs the presence of iron. Ferroptosis is a controlled cell death process that adheres to certain rules and regulations. The inhibition of System Xc- and the involvement of GPX4 are two of the primary areas of exploration that are engaged in the process of ferroptosis. This review explores the treatments that are used to treat ferroptosis in a range of malignancies, with a particular focus on breast carcinoma. Attention is paid to certain pathways, such as the FSP1-independent regulation of glutathione, involvement of cholesterol, and the prominin 2-MVB/exosome-ferritin pathway. Ferroptosis plays a key role in resistance to tumor therapy. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), a common plasticizer, is categorized as a neurotoxic compound. Its impact on individuals exhibits sex-linked variations. Several biological and environmental factors impact the degree of toxicity. Moreover, nutritional factors have profound influence on toxicity outcome. BPA has been demonstrated to be an obesogen. However, research on the potential role of obesity as a confounding factor in BPA toxicity is lacking. We studied the neurodegenerative effects in high-fat diet (HFD)-induced obese female rats after exposure to BPA (10 mg/L via drinking water for 90 days). Four groups were taken in this study – Control, HFD, HFD + BPA and BPA. Cognitive function was evaluated through novel object recognition (NOR) test. Inflammatory changes in brain, and changes in hormonal level, lipid profile, glucose tolerance, oxidative stress, and antioxidants were also determined. HFD + BPA group rats showed a significant decline in memory function in NOR test. The cerebral cortex (CC) of the brain showed increased neurodegenerative changes as measured by microtubule-associated protein-2 (MAP-2) accompanied by histopathological confirmation. The increased level of neuroinflammation was demonstrated by microglial activation (Iba-1) and protein expression of nuclear factor– kappa B (NF-КB) in the brain. Obesity also caused significant (p < 0.05) increase in lipid peroxidation accompanied by reduced activities of antioxidant enzymes (glutathione S-transferase, catalase and glutathione peroxidase) and decrease in reduced-glutathione (p < 0.05) when compared to non-obese rats with BPA treatment. Overall, study revealed that obesity serves as a risk factor in the toxicity of BPA which may exacerbate the progression of neurological diseases. [ABSTRACT FROM AUTHOR]

Acetochlor, as a commonly used pre‐emergent herbicide, can be toxic to crops and affect production if used improperly. However, the toxic mechanism of acetochlor on plants is not fully understood. The present study used a combination of transcriptomic analysis and physiological measurements to investigate the effects of short‐term (15‐day) exposure to different concentrations of acetochlor (1, 10, 20 mg/kg) on the morphology, physiology, and transcriptional levels of pea seedlings, aiming to elucidate the toxic response and resistance mechanisms in pea seedlings under herbicide stress. The results showed that the toxicity of acetochlor to pea seedlings was dose‐dependent, manifested as dwarfing and stem base browning with increasing concentrations, especially at 10 mg/kg and above. Analysis of the antioxidant system showed that from the 1 mg/kg treatment, malondialdehyde, superoxide dismutase, peroxidase, and glutathione peroxidase in peas increased with increasing concentrations of acetochlor, indicating oxidative damage. Analysis of the glutathione (GSH) metabolism system showed that under 10 mg/kg treatment, the GSH content of pea plants significantly increased, and GSH transferase activity and gene expression were significantly induced, indicating a detoxification response in plants. Transcriptomic analysis showed that after acetochlor treatment, differentially expressed genes in peas were significantly enriched in the phenylpropane metabolic pathway, and the levels of key metabolites (flavonoids and lignin) were increased. In addition, we found that acetochlor‐induced dwarfing of pea seedlings may be related to gibberellin signal transduction. Environ Toxicol Chem 2024;43:2005–2019. © 2024 SETAC [ABSTRACT FROM AUTHOR]

Selenium (Se) is an essential trace element associated with both beneficial and detrimental health effects; deficiency and uncontrolled self-supplementation are both issues of concern. Secondary analysis of a randomized controlled trial and observational studies indicate that Se is a potential risk factor for type 2 diabetes mellitus (T2D). The association between Se and diabetes may be sex specific, with potentially increased risk in men and an inverse association in women, particularly for gestational diabetes mellitus during pregnancy. Recent observational evidence suggests that high Se status favorably affects all-cause mortality risk in patients with manifest diabetes and reduces macrovascular T2D. Selenium (Se) is an essential trace element, which is inserted as selenocysteine (Sec) into selenoproteins during biosynthesis, orchestrating their expression and activity. Se is associated with both beneficial and detrimental health effects; deficient supply or uncontrolled supplementation raises concerns. In particular, Se was associated with an increased incidence of type 2 diabetes (T2D) in a secondary analysis of a randomized controlled trial (RCT). In this review, we discuss the intricate relationship between Se and diabetes and the limitations of the available clinical and experimental studies. Recent evidence points to sexual dimorphism and an association of Se deficiency with gestational diabetes mellitus (GDM). We highlight the emerging evidence linking high Se status with improved prognosis in patients with T2D and lower risk of macrovascular complications. [ABSTRACT FROM AUTHOR]

The effectiveness of tumor treatment using reactive oxygen species as the primary therapeutic medium is hindered by limitations of tumor microenvironment (TME), such as intrinsic hypoxia in photodynamic therapy (PDT) and overproduction of reducing glutathione (GSH) in chemodynamic therapy (CDT). Herein, we fabricate metal-polyphenol self-assembled nanodots (Fe@BDP NDs) guided by second near-infrared (NIR-II) fluorescence imaging. The Fe@BDP NDs are designed for synergistic combination of type-I PDT and CDT-amplified ferroptosis. In a mildly acidic TME, Fe@BDP NDs demonstrate great Fenton activity, leading to the generation of highly toxic hydroxyl radicals from overproduced hydrogen peroxide in tumor cells. Furthermore, Fe@BDP NDs show favorable efficacy in type-I PDT, even in tolerating tumor hypoxia, generating active superoxide anion upon exposure to 808 nm laser irradiation. The significant efficiency in reactive oxygen species (ROS) products results in the oxidation of sensitive polyunsaturated fatty acids, accelerating lethal lipid peroxidation (LPO) bioprocess. Additionally, Fe@BDP NDs illustrate an outstanding capability for GSH depletion, causing the inactivation of glutathione peroxidase 4 and further promoting lethal LPO. The synergistic type-I photodynamic and chemodynamic cytotoxicity effectively trigger irreversible ferroptosis by disrupting the intracellular redox homeostasis. Moreover, Fe@BDP NDs demonstrate charming NIR-II fluorescence imaging capability and effectively accumulated at the tumor site, visualizing the distribution of Fe@BDP NDs and the treatment process. The chemo/photo-dynamic-amplified ferroptotic efficacy of Fe@BDP NDs was evidenced both in vitro and in vivo. This study presents a compelling approach to intensify ferroptosis via visualized CDT and PDT. In this study, we detailed the fabrication of metal-polyphenol self-assembled nanodots (Fe@BDP NDs) guided by second near-infrared (NIR-II) fluorescence imaging, aiming to intensify ferroptosis via the synergistic combination of type-I PDT and CDT. In a mildly acidic TME, Fe@BDP NDs exhibited significant Fenton activity, resulting in the generation of highly toxic •OH from overproduced H 2 O 2 in tumor cells. Fe@BDP NDs possessed a remarkable capability for GSH depletion, resulting in the inactivation of glutathione peroxidase 4 (GPX4) and further accelerating lethal LPO. This study presented a compelling approach to intensify ferroptosis via visualized CDT and PDT. [Display omitted] [ABSTRACT FROM AUTHOR]

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λ-cyhalothrin, a synthetic type II pyrethroid, has become increasingly popular for control of aphids, butterfly larvae, and beetles, replacing other agricultural chemicals. As a result of which, residues of this synthetic pesticide are being reported across the globe in natural water, which poses a serious threat to aquatic life. Therefore, the present study was designed to understand the toxicity effects of λ-cyhalothrin on behaviour, oxidative stress and neurotoxicity in a vertebrate aquatic model, zebrafish (Danio rerio). The fish were exposed to 0.129, 0.194 and 0.388 µg/L corresponding to 5%, 10% and 20% of 96hLC50 (1.94 µg/L) for 28 days. Upon exposure to the highest concentration (0.388 µg/L), the test animal exhibited significant alterations in behavioural patterns like number of entries to the top zone (n), decrease in average speed (m/s) and decrease in time spent in top zone (s). Moreover, the shoaling test demonstrated a significant decrease (p < 0.05) in the relative time spent by the tested fish (%) near the stimulus fish. The change in behavioural alterations might be linked to a significant decrease (p < 0.05) in the brain acetylcholine esterase activity. Furthermore, the present study also illustrates oxidative stress exerted by λ-cyhalothrin through an increase in the production of reactive oxygen species, which is again clearly depicted by a significant increase (p < 0.05) in Superoxide dismutase, Catalase and Glutathione peroxidase activities. Overall, the present study systematically demonstrates the chronic effects of λ-cyhalothrin on adult fish behaviour and physiology, which will contribute to assessing the risks of λ-cyhalothrin to organismal health. [ABSTRACT FROM AUTHOR]

Titanium dioxide nanoparticles (TiO2) are released into the natural waters in different ways and cause toxicity to aquatic life. Although various studies have reported the toxicity of nanoparticles for aquatic animals, there is limited information regarding the effects of environmental factors, especially salinity, on their toxicity. Simultaneous effects of TiNPs and water salinity were studied in the Pacific oyster, Crassostrea gigas. Oysters were exposed to sub-lethal concentrations of TiNPs (low concentration: 50 µg/l, middle concentration: 500 µg/l, high concentration: 5000 µg/l) at different water salinities (Extremely low salinity: 5 g/l, low salinity: 15 g/l, middle salinity: 25 g/l, high salinity (normal salinity): 35 g/l) for 96 h. After nano-TiO2 exposure, the immune components in hemolymph (total hemocyte concentration [THC], phagocytosis), antioxidant enzyme activities in digestive gland (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase), oxidation stress index (malondialdehyde) in gills and the expression of immune-related genes (Vav-3 protein, cofilin, Galectin 4, pro-Cathepsin L, Rho protein, Ficolin, LPS/-1,3-glucan protein, Lysozyme, Defensin) in hemocytes were measured. The THC, phagocytosis, antioxidant enzyme activities, and immune-related gene expressions mostly decreased at salinities of 5 and 15 g/l in response to 500–5000 µg/l nano-TiO2 compared to non-exposed oysters and 50 µg/l nano-TiO2 group. An increase in water salinity up to 35 g/l mitigated the depressing effects of the nano-TiO2 on the immune and antioxidant components of the oysters. Exposure of oysters to 500–5000 µg/l nano-TiO2-induced oxidative stress at salinities of 5 and 15, since malondialdehyde levels were higher in these treatments compared to control and those in 50 µg/l nano-TiO2 group. The increase of salinity up to 35 g/l ameliorated the TiO2-induced oxidative stress. The results of the present study showed that the toxic impacts of nano-TiO2 can be ameliorated in the Pacific oyster with increase in water salinity, as the immune components, antioxidant enzyme activities recovered and oxidative stress mitigated when the salinity increased up to 35 g/l. [ABSTRACT FROM AUTHOR]

Spotlighting the current state of largemouth bass (Micropterus salmoides) aquaculture, this study exhibited the effects of steroidal saponins (SS) on the liver health of largemouth bass under high‐temperature stress. The study consisted of two experiments: the first trial was designed to evaluate the growth performance of fish fed the experimental diets containing SS 0% and 0.1% (SS0 and SS0.1) for 30 days. And then, the second trial was used to evaluate the health of the livers of these fish under high‐temperature (34°C) stress which lasts for 1 week, and the groups were named as SS0, HSS0, SS0.1, and HSS0.1, respectively. In the first feeding trial, except for the higher feeding rate observed in the SS0.1 group (P < 0.05), no significant difference was observed between the groups SS0 and SS0.1 in survival rate, weight gain rate, specific growth rate, and feed conversion rate, respectively. After 1 week of high‐temperature stress, the specific growth rate and weight gain rate of fish were significantly lowered in the HSS0 and HSS0.1 groups (P < 0.05). In terms of feeding rate, the SS0.1 and HSS0.1 groups were significantly higher than the other two groups (P < 0.05). Under high‐temperature stress, gene expressions of caspase-3, caspase-8, caspase-9, tnf-α, il-8, and hsp70 were significantly downregulated in the liver of largemouth bass in the HSS0.1 group (P < 0.05). The activities of antioxidant enzymes, including catalase, total superoxide dismutase, and glutathione peroxidase in the liver, were significantly increased, while the serum enzyme activities of aspartate aminotransferase and alanine aminotransferase were significantly decreased in the HSS0.1 group (P < 0.05). Compared to the HSS0 group, hepatic vacuolization areas of fish in the HSS0.1 group were improved (P < 0.05). Therefore, the results of the study supported that the 0.1% SS used in largemouth bass diet for 30 days could strengthen the liver and body health and help fish resist heat stress. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a major public health problem worldwide that still lacks effective treatments. Recent studies have suggested that ferroptosis is a key mediator of AKI due to its activation of lipid peroxidation. Therefore, we hypothesized that antiferroptosis agents might be a novel potential therapeutic strategy for AKI. Herein, we demonstrated that liquiritigenin (LG), an active ingredient of liquorice, improves renal function by inhibiting vitamin K epoxide reductase complex subunit 1 (VKORC1)-mediated ferroptosis, both in vivo and in vitro. In a folic acid-induced murine AKI model, after a single pre-treatment intravenous injection, LG markedly alleviated the loss of renal function through suppressing ferroptosis induced by iron accumulation. LG prevented mitochondrial morphological changes and upregulated glutathione and glutathione peroxidase 4 levels, while downregulating malonaldehyde and divalent iron levels. An in vitro RNA-sequence analysis suggested that the protective role of LG may involve upregulation of VKORC1. Moreover, knockdown of VKORC1 diminished the renal protective and antiferroptosis roles of LG. Collectively, our findings demonstrated that LG protected against AKI by inhibiting VKORC1-mediated ferroptosis. This suggests that inhibiting ferroptosis might be a novel therapeutic approach in the future. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusionDiabetic cataract (DC) is a major cause of blindness worldwide. Prion protein (PRNP) was proved to be up-regulated and hypomethylated in DC samples. Here, we investigated whether PRNP was involved in DC progression in N6-methyladenosine (m6A)-dependent manner, and its potential mechanisms.Levels of genes and proteins were assayed using qRT-PCR and western blotting. Cell proliferation and apoptosis were determined using Cell Counting Kit-8 assay, 5-thynyl-2’-deoxyuridine (EdU) assay, and flow cytometry, respectively. Oxidative stress was analyzed by measuring the production of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and malondialdehyde (MDA). The m6A modification was determined by RNA immunoprecipitation (Me-RIP) assay. The interaction between RBM15 (RNA binding motif protein 15) and PRNP was probed using RIP assay.PRNP was highly expressed in DC patients and HG-induced HLECs. Functionally, PRNP deficiency reversed HG-induced apoptosis and oxidative stress in HLECs. Mechanistically, RBM15 induced PRNP m6A modification and directly bound to PRNP. Knockdown of RBM15 abolished HG-induced apoptotic and oxidative injury in HLECs, while these effects were rescued after PRNP overexpression.RBM15 silencing suppressed HG-induced lens epithelial cell injury by regulating PRNP in an m6A-mediated manner, hinting a novel therapeutic strategy for DC patients. [ABSTRACT FROM AUTHOR]

Perfluorooctanoic acid (PFOA) is a surfactant that is detected in small quantities across various environments away from its manufacturing zones. Despite the widespread detection of PFOA in aquatic ecosystems, the impact of this compound on phytoplankton populations remains poorly understood. This study aimed to determine the physiological effects of PFOA on Microcystis aeruginosa. The cyanobacterium was exposed to 1‒10 000 μg l‒1 PFOA for 7 days under controlled laboratory conditions. The EC50 of PFOA for the test species after 7 days of exposure was 30.03 μg l‒1. Cell density significantly decreased at all PFOA concentrations (1‒10 000 μg l‒1). Chlorophyll a and carotenoid concentrations increased on day 1 (except for 1 μg l‒1, the lowest PFOA treatment) but then decreased across all treatment concentrations on day 7 of the experiment. When M. aeruginosa was exposed to PFOA, the total lipid, protein and carbohydrate content generally increased across all treatment concentrations. The concentration of intracellular hydrogen peroxide increased with increasing surfactant concentrations. In different treatments, lipid peroxidation increased, with 100 μg l‒1 PFOA producing the highest malondialdehyde content. Peroxidase and glutathione S-transferase activities increased across all treatment concentrations, demonstrating progressive changes consistent with the increase in reactive oxygen species observed. Total microcystin concentration increased in cultures exposed to 1000 and 10 000 µg l‒1 PFOA. These findings suggest that PFOA can adversely affect the survival of M. aeruginosa populations in contaminated aquatic ecosystems, with potential cascading effects on the general health of the environment. [ABSTRACT FROM AUTHOR]

The pathogenesis of systemic sclerosis (SSC) fibrosis involves the rapid proliferation of skin fibroblasts, and current anti-fibrotic treatments are limited. This study investigated the relationship between ferroptosis and SSC skin fibroblasts. We observed that erastin-induced ferroptosis was suppressed in SSC fibroblasts. RSL3, a direct inhibitor of Glutathione Peroxidase 4 (GPX4), significantly reduced the viability of the fibroblasts, and upregulation of GPX4 in the SSC fibroblasts contributed to ferroptosis resistance. Furthermore, we demonstrated that transferrin receptor 1 (TfR1) was a crucial transporter for iron deposition in the fibroblasts. Collectively, our results highlight that GPX4 inhibition could enhance the sensitivity to ferroptosis by SSC fibroblasts, which showed distinct characteristics of iron metabolism that were not observed in normal fibroblasts in this study. Taken together, these results suggest that targeting ferroptosis could be a therapeutic strategy for the treatment of SSC. [Display omitted] • Upregulation of GPX4 in SSC skin fibroblasts contributed to Erastin resistance. • TfR1 was a crucial transporter for iron deposition in SSC skin fibroblasts. • Downregulation of Ft-H and Ft-L indicated that cellular iron storage was inhibited in SSC fibroblasts. • NRF2 was decreased in SSC fibroblasts. [ABSTRACT FROM AUTHOR]

Current treatments for rheumatoid arthritis produce untoward effects; thus, considerable effort has been made to recognize effective herbal medicines against the condition. In the present study, the therapeutic effect of Diospyros kaki fruit hydroalcoholic extract (DFHE) on complete Freund's adjuvant (CFA)‐induced arthritis in rats was investigated. The extract was characterized using liquid chromatography–electrospray mass spectrometry (LC‐ESIMS). Male Wistar rats were grouped as follows (eight rats in each): control, CFA, CFA + indomethacin (5 mg/kg), CFA + DFHE (50 mg/kg), and CFA + DFHE (100 mg/kg). Paw volume, mechanical allodynia, thermal hyperalgesia, and arthritis score were evaluated. Serum levels of malondialdehyde (MDA), thiol groups, tumor necrosis factor‐alpha (TNF‐α), as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were evaluated. Carotenoids were found to be the major components of DFHE. Administration of DFHE (100 mg/kg) significantly decreased arthritis score, paw volume, and thermal hyperalgesia, and improved mechanical allodynia. MDA and TNF‐α levels were decreased while thiol levels and SOD and GPx activities were increased in DFHE‐treated groups compared to the CFA group. These results suggest that D. kaki extract caused an improvement in clinical signs of rheumatoid arthritis symptoms possibly through suppression of oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

The liver-derived selenium (Se) transporter selenoprotein P (SELENOP) declines in critical illness as a negative acute phase reactant and has recently been identified as an autoantigen. Hepatic selenoprotein biosynthesis and cotranslational selenocysteine insertion are sensitive to inflammation, therapeutic drugs, Se deficiency, and other modifiers. As severe burn injury induces a heavy inflammatory burden with concomitant Se depletion, we hypothesized an impairment of selenoprotein biosynthesis in the acute postburn phase, potentially triggering the development of autoantibodies to SELENOP (SELENOP-aAb). To test this hypothesis, longitudinal serum samples from severely burned patients were analyzed over a period of six months. Newly occurring SELENOP-aAb were detected in 8.4% (7/83) of the burn patients, with onset not earlier than two weeks after injury. Prevalence of SELENOP-aAb was associated with injury severity, as aAb-positive patients have suffered more severe burns than their aAb-negative counterparts (median [IQR] ABSI: 11 [7-12] vs. 7 [5.8-8], p = 0.023). Autoimmunity to SELENOP was not associated with differences in total serum Se or SELENOP concentrations. A positive correlation of kidney-derived glutathione peroxidase (GPx3) with serum SELENOP was not present in the patients with SELENOP-aAb, who showed delayed normalization of GPx3 activity post-burn. Overall, the data suggest that SELENOP-aAb emerge after severe injury in a subset of patients and have antagonistic effects on Se transport. The nature of burn injury as a sudden event allowed a time-resolved analysis of a direct trigger for new-onset SELENOP-aAb, which may be relevant for severely affected patients requiring intensified acute and long-term care. [ABSTRACT FROM AUTHOR]

Oxaliplatin (OXA) as the platinum-based agent induces the cumulative neuropathy including functional impairment and neuropathic pain. OXA treatment triggered oxidative stress and inflammatory reaction in the spinal cord. Puerarin as a natural product has the neuroprotective effect on neuropathic pain. Hence, the roles and mechanisms of Pue on OXA induced neuropathic pain were studied. In this study, OXA-induced neuropathic pain mouse model was constructed by oxaliplatin injection for 5 consecutive days and two cycles. Pue (10 mg/kg) was administered intraperitoneally for seven consecutive days. The changes of behavior, morphology and levels of related proteins were detected. As a result, OXA-induced mice exhibited as the increased pain hypersensitivity, the impaired motor coordination, the activated NLRP3 inflammasome mediated inflammation and the suppressed nuclear factor erythroid 2-related factor 2 (Nrf2) mediated antioxidative reaction in the spinal cord (P<0.05 vs Control). After Pue administration, the mechanical pain threshold, thermal pain latency, spontaneous pain number and motor latency were improved (P<0.05 vs OXA). In the spinal cord, Pue administration reduced the levels of inflammatory elements, increased the levels of antioxidative elements and decreased the levels of oxidative factors (P<0.05 vs OXA). Furthermore, Pue also bind with Nrf2 and increased the association of Nrf2 to glutathione peroxidase 4 (GPX4). In summary, Pue alleviates oxaliplatin induced neuropathic pain by enhancing Nrf2/GPX4-mediated antioxidant response and suppressing inflammatory reaction in the spinal cord. [ABSTRACT FROM AUTHOR]

Metronomic chemotherapy with cyclophosphamide (Cpp) has shown promising results in cancer protocols. These lower and prolonged doses have antiangiogenic, pro-cytotoxic, and moderate secondary effects. Molecular iodine (I2) reduces the viability of cancer cells and, with chemotherapeutic agents, activates the antitumoral immune response and diminishes side effects. The present work evaluates the adjuvant of oral I2 with Cpp using a murine model of mammary cancer. Female Sprague Dawley rats with 7,12-dimethylbenzantracene-induced tumors received Cpp intraperitoneal (50 and 70 mg/kg two times/week, iCpp50 and iCpp70) and oral (0.03%; 50 mg/Kg; oCpp50) doses. I2 (0.05%, 50 mg/100 mL) and oCpp50 were offered in drinking water for three weeks. iCpp70 was the most efficient antitumoral dose but generated severe body weight loss and hemorrhagic cystitis (HC). I2 prevented body weight loss, exhibited adjuvant actions with Cpp, decreasing tumor growth, and canceled HC mechanisms, including decreases in vascular endothelial growth factor (VEGF) and Survivin expression. oCpp50 + I2 diminished angiogenic signals (CD34, vessel-length, and VEGF content) and proinflammatory cytokines (interleukin-10 and tumor necrosis factor-alpha) and increased cytotoxic (lymphocytic infiltration, CD8+ cells, Tbet, and interferon-gamma) and antioxidant markers (nuclear erythroid factor-2 and glutathione peroxidase). I2 enhances the effectiveness of oCpp, making it a compelling candidate for a clinical protocol. [ABSTRACT FROM AUTHOR]

Erastin (ER) induces cell death through the formation of reactive oxygen species (ROS), resulting in ferroptosis. Ferroptosis is characterized by an accumulation of ROS within the cell, leading to an iron-dependent oxidative damage-mediated cell death. ER-induced ferroptosis may have potential as an alternative for ovarian cancers that have become resistant due to the presence of Ras mutation or multi-drug resistance1 (MDR1) gene expression. We used K-Ras mutant human ovarian tumor OVCAR-8 and NCI/ADR-RES, P-glycoprotein-expressing cells, to study the mechanisms of ER-induced cell death. We used these cell lines as NCI/ADR-RES cells also overexpresses superoxide dismutase, catalase, glutathione peroxidase, and transferase compared to OVCAR-8 cells, leading to the detoxification of reactive oxygen species. We found that ER was similarly cytotoxic to both cells. Ferrostatin, an inhibitor of ferroptosis, reduced ER cytotoxicity. In contrast, RSL3 (RAS-Selective Ligand3), an inducer of ferroptosis, markedly enhanced ER cytotoxicity in both cells. More ROS was detected in OVCAR-8 cells than NCI/ADR-RES cells, causing more malondialdehyde (MDA) formation in OVCAR-8 cells than in NCI/ADR-RES cells. RSL3, which was more cytotoxic to NCI/ADR-RES cells, significantly enhanced MDA formation in both cells, suggesting that glutathione peroxidase 4 (GPX4) was involved in ER-mediated ferroptosis. ER treatment modulated several ferroptosis-related genes (e.g., CHAC1, GSR, and HMOX1/OX1) in both cells. Our study indicates that ER-induced ferroptotic cell death may be mediated similarly in both NCI/ADR-RES and OVCAR-8 cells. Additionally, our results indicate that ER is not a substrate of P-gp and that combinations of ER and RSL3 may hold promise as more effective treatment routes for ovarian cancers, including those that are resistant to other current therapeutic agents. [ABSTRACT FROM AUTHOR]

In rats with unilateral nephrectomy and cardiac dysfunction, renal function deteriorates at an accelerated rate, as evidenced by increased proteinuria. Whether myocardial infarct-induced heart failure (HF) exacerbates renal injury in hypertensive rats with mild renal injury has not been reported. Rats underwent either coronary ligation or sham surgery. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomly divided into two groups. Group 1 was the sham group, in which the rats underwent thoracotomy without ligation of the coronary artery. Group 2 underwent coronary artery ligation. The rats in group 2 underwent coronary artery ligation on week 0. The experiment lasted 12 weeks. Urine was collected in metabolic cages over a 24-h period. Urine was collected from the rats 2 days before the end of the experiment, and the ratio of urinary protein to urinary creatinine was measured in the clinical laboratory. All rats were examined by echocardiogram one day before the end of the experiment. On the last day of the experiment, blood was collected and sent to the laboratory for analysis. Hematoxylin–eosin (HE) and periodic acid-Schiff (PAS) staining were performed on heart and kidney sections. The ejection fraction in group 2 was lower than that in group 1 (P < 0.001). The urinary albumin to creatinine ratio in group 2 was greater than that in group 1 (P < 0.001). The urea and creatinine levels in group 1 were significantly lower than those in group 2 (P < 0.01). The levels of brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C were greater in the second group than in the first group (P < 0.05). The interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels in group 2 were significantly greater than those in group 1 (P < 0.001). The malondialdehyde (MDA) levels in Group 2 were greater than those in Group 1 (P < 0.01). The glutathione peroxidase (GSH-Px) levels in Group 2 were lower than those in Group 1 (P < 0.05). The level of angiotensin II (AT-II) in group 1 was lower than that in group 2 (P < 0.001). Cardiac dysfunction secondary to myocardial infarction could induce cardiorenal interactions in SHRs. It could be interpreted by the activation of oxidative stress, changes in inflammation and alteration of renin–angiotensin–aldosterone system. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the effects of selenium nanoparticle (Se-NP) supplementation on the growth performance, carcass composition, antioxidant status, hepatic enzyme activities, and immunity of Cirrhinus mrigala. For this purpose, fish with an average initial weight of 7.44 ± 0.04 g were fed five experimental diets containing 0 (control), 0.25, 0.5, 1, and 2 mg kg-1 Se-NPs diets for 90 days. The analysed selenium (Se) contents of the diets were 0.35, 0.64, 0.92, 1.43, and 2.39 mg kg-1. Twenty five fish were randomly distributed in each of 5 aquarium (36 × 23.7 × 24.3 inches) in triplicate. The results showed that supplementation with Se up to 0.92 mg/kg significantly increased (p<0.05) weight gain, weight gain% (WG%), and specific growth rate (SGR) by 34%, 33%, and 16%, respectively, compared to the control diet. Dietary Se concentrations up to 0.92 mg/kg significantly increased the crude protein and crude fat and reduced (p<0.05) the moisture content as compared to the control group. Fish fed 0.92 mg kg-1 Se had significantly lower malondialdehyde (MDA) contents and higher activities of catalase, superoxide dismutase, and glutathione peroxidase in liver and serum as compared to other experimental diets. Moreover, a significant increase (p<0.05) in the level of serum immunoglobulin and lysozyme (LYZ) activity was recorded in fish fed 0.92 mg/kg Se diet. Moreover, the highest (p<0.05) values of aspartate transaminase (AST) and alanine transaminase (ALT) were recorded in fish fed 2.39 mg/kg Se level. However, serum alkaline phosphatase (ALP) activity remained unaffected by dietary treatment. Broken-line regression analysis indicated that 0.83 mg/kg Se is required for the optimum growth performance of C. mrigala. [ABSTRACT FROM AUTHOR]

As rate-limiting enzymes of peroxisomal b-oxidation, acyl-coenzyme A oxidase (ACOXs) play vital roles in maintaining energy homeostasis and regulating reactive oxygen species (ROS) metabolism. However, there are no studies on the functions of ACOXs in crustaceans. In the present study, four full-length cDNA sequences of acoxs, namely the acox-1a (2403 bp), acox-1b (2733 bp), acox-3a (2878 bp) and acox-3b (3445 bp), were successfully isolated from mud crab Scylla paramamosain, which encoded 666, 673, 701 and 658 amino acids, respectively. Sequence analysis showed that the ACOX-1a, ACOX-1b and ACOX-3a possessed conserved structural domains like FAD-binding motif, fatty acyl CoA oxidase domain and peroxisomal targeting signal, while the ACOX-3b lacked peroxisomal targeting signal. Results of phylogenetic tree indicated that the four ACOXs of mud crab grouped gathered with their corresponding orthologues from crustaceans. The acox-1a, acox-3a and acox-3b were highly expressed in hepatopancreas, and the acox-1b was mainly distributed in muscle and hepatopancreas. Compared with feeding groups, the expression levels of acox-1a, acox-3a and acox-3b in hepatopancreas and acox-3a in muscle were markedly up-regulated in fasting groups, suggesting that the acoxs had significant effects in modulating energy balance during fasting. In addition, fasting significantly increased the transcriptional levels of nuclear factor erythroid 2-related factor (nrf2) and its downstream antioxidant genes (catalase (cat), glutathione peroxidase (gpx) and glutathione S-transferase (gst)) to improve antioxidant capacity for removing excessive ROS produced by ACOX-mediated peroxisomal b-oxidation. These results would be conducive to providing new insights into evolutionary characteristics and functions of acoxs in crustaceans. [ABSTRACT FROM AUTHOR]

A 60 days study was conducted to evaluate the physiological response of indigenous species Labeo rohita (LR) and indigenous predator Chitala chitala (CC) in presence of an invasive species Piaractus brachypomus (PB). Two treatment groups as LR + PB (T1) and LR + PB + CC (T2) with individual control groups as T0LR, T0PB and T0CC were designed in triplicates. Fingerlings of LR, PB and CC were randomly distributed into 15 circular tanks with a stocking ratio of 1:1 and 1:1:0.3 in T1 and T2 group, respectively and 10 nos. each of LR, PB and CC in respective control groups. At first 15 min of the experiment, cortisol level was found significantly (P < 0.05) higher in all three experimental fishes in T1 and T2 groups. With the experimental duration, the level of stress hormone (cortisol), oxidative stress enzymes (superoxide dismutase, catalase, and glutathione peroxidase), tissue metabolic enzymes (lactate dehydrogenase and malate dehydrogenase), serum metabolic enzymes (transaminase enzymes) and blood glucose level were significantly (P < 0.05) increased in T1 and T2 groups for LR and CC whereas, no variation (P > 0.05) were observed for PB in both T1 and T2 groups. The total antioxidant capacity (TAC), liver glycogen, total protein, albumin and globulin were found to be significantly (P < 0.05) decreased in LR in the presence of PB and CC. The present study provides a preliminary insight into the biological interaction between native and invasive species and their physiological responses in the presence of native predator with higher trophic index. Thus, the results of the study suggest the superior traits of invasive P. brachypomus try to dominate the other two native species by negatively influencing the native fauna even with a higher trophic index (C. chitala). [ABSTRACT FROM AUTHOR]

Introduction: This present research was designed to investigate the antiinflammatory and immune-modulatory effects of a 50% hydroethanolic extract of "Gola" guava fruit (GF50%) and guava leaf (GL50%) against papain-induced knee osteoarthritis (KOA). Methods: Sixty Sprague-Dawley rats were divided into five groups (10 rats/group): T0 (negative control), T1 (positive control), T2 (200 mg/kg GF50%), T3 (400 mg/kg GF50%), T4 (200 mg/kg GL50%), and T5 (400 mg/kg GL50%). Physical parameters were evaluated throughout the trial, while biochemical, histopathological, and radiographic analyses were performed at 0, 15, and 30 days. The histopathological and radiographic analyses were evaluated using the Osteoarthritis Research Society International (OARSI) score and Kellgren-Lawrence (KL) classification systems, respectively. Results and discussion: The T1 group demonstrated a significant increase in knee diameter, confirming successful OA induction. The T5 group maintained a significantly lower body weight at day 30, and the T3 group exhibited the highest weight gain. The high dose of GL50% (400 mg/kg) effectively reduced knee inflammation and significantly downregulated myeloperoxidase (MPO), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In contrast, it significantly (p < 0.001) upregulated the serum and knee capsule tissue superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). In addition, histopathological and X-ray examinations also confirmed the chondroprotective potential of GL50% extract against OA. Consequently, 400 mg/kg GL50% exhibited anti-inflammatory and chondroprotective potential by lowering oxidative stress and pro-inflammatory cytokines and elevating antioxidant status. These findings could provide a theoretical basis for understanding the mechanism and potential medicinal value of guava fruit and leaf in treating KOA. [ABSTRACT FROM AUTHOR]

Background: Echis ocellatus envenoming is potentially toxic initiating clinical damages on male reproductive system. Kaempferol is a therapeutic agent with neutralizing potentials on snake venom toxins. This study investigated the antagonistic effect of kaempferol on E. ocellatus venom (EoV)-induced reproductive toxicities. Methods: Fifty adult male rats were sorted at random into five groups of ten rats for this study. The control rats were allotted to group 1, while rats in groups 2–5 were injected with 0.22 mg/kg bw (LD50) of EoV intraperitoneally. Rats in group 2 were not treated while groups 3–5 rats were treated with serum antivenom (0.2 ml), and 4 and 8 mg/kg bw of kaempferol post envenoming, respectively. Results: EoV actuated reproductive toxicity, significantly decreased sperm parameters, and enhanced inflammatory, oxidative stress, and apoptotic biomarkers in reproductive organs of untreated envenomed rats. However, treatment with kaempferol alleviated the venom-induced reproductive disorders with a dose dependent effect. Kaempferol significantly increased the testicular weight, organo-somatic index, sperm parameters, and normalized the levels of serum luteinizing hormone, testosterone, and follicle stimulating hormone. Kaempferol ameliorated testicular and epididymal oxidative stress as evidenced by significant decrease in malondialdehyde (MDA) levels, enhancement of reduced glutathione (GSH) levels, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities. The inflammatory biomarkers; nitric oxide (NO) levels and myeloperoxidase activity (MPO), and apoptotic biomarkers; caspase 3 and caspase 9 activities were substantially suppressed in the testis and epididymis of envenomed rats treated with kaempferol. Conclusion: Results revealed kaempferol as a potential remedial agent against reproductive toxicity that could manifest post-viper envenoming. [ABSTRACT FROM AUTHOR]

Macrobrachium nipponense is an important commercial freshwater species in China. However, the ability of alkali tolerance of M. nipponense is insufficient to culture in the major saline-alkali water source in China. Thus, it is urgently needed to perform the genetic improvement of alkali tolerance in this species. In the present study, we aimed to analyse the effects of alkali treatment on gills in this species after 96 h alkalinity exposure under the alkali concentrations of 0 mmol/L, 4 mmol/L, 8 mmol/L, and 12 mmol/L through performing the histological observations, measurement of antioxidant enzymes, metabolic profiling analysis, and transcriptome profiling analysis. The results of the present study revealed that alkali treatment stimulated the contents of malondialdehyde, glutathione, glutathione peroxidase in gills, indicating these antioxidant enzymes plays essential roles in the protection of body from the damage, caused by the alkali treatment. In addition, high concentration of alkali treatment (> 8 mmol/L) resulted in the damage of gill membrane and haemolymph vessel, affecting the normal respiratory function of gill. Metabolic profiling analysis revealed that Metabolic pathways, Biosynthesis of secondary metabolites, Biosynthesis of plant secondary metabolites, Microbial metabolism in diverse environments, Biosynthesis of amino acids were identified as the main enriched metabolic pathways of differentially expressed metabolites, which are consistent with the previous publications, treated by the various environmental factors. Transcriptome profiling analyses revealed that the alkali concentration of 12 mmol/L has more regulatory effects on the changes of gene expression than the other alkali concentrations. KEGG analysis revealed that Phagosome, Lysosome, Glycolysis/Gluconeogenesis, Purine Metabolism, Amino sugar and nucleotide sugar metabolism, and Endocytosis were identified as the main enriched metabolic pathways in the present study, predicting these metabolic pathways may be involved in the adaption of alkali treatment in M. nipponense. Phagosome, Lysosome, Purine Metabolism, and Endocytosis are immune-related metabolic pathways, while Glycolysis/Gluconeogenesis, and Amino sugar and nucleotide sugar metabolism are energy metabolism-related metabolic pathways. Quantitative PCR analyses of differentially expressed genes (DEGs) verified the accuracy of the RNA-Seq. Alkali treatment significantly stimulated the expressions of DEGs from the metabolic pathways of Phagosome and Lysosome, suggesting Phagosome and Lysosome play essential roles in the regulation of alkali tolerance in this species, as well as the genes from these metabolic pathways. The present study identified the effects of alkali treatment on gills, providing valuable evidences for the genetic improvement of alkali tolerance in M. nipponense. [ABSTRACT FROM AUTHOR]

Cardiotoxicity is the leading side effect of anthracycline‐based chemotherapy. Therefore, it has gained importance to reveal chemotherapy‐supporting strategies and reliable agents with their mechanisms of action. Tannic acid (TA), a naturally occurring plant polyphenol, has diverse physiological effects, including anti‐inflammatory, anticarcinogenic, antioxidant, and radical scavenging properties. Therefore, this study was designed to investigate whether TA exerts a protective effect on mechanisms contributing to anthracycline‐induced cardiotoxicity in rat heart tissues exposed to doxorubicin (DOX). Rats were randomly divided into control and experimental groups and treated with (18 mg/kg) DOX, TA (50 mg/kg), and DOX + TA during the 2 weeks. Cardiac gene markers and mitochondrial DNA (mtDNA) content were evaluated in the heart tissues of all animals. In addition to major metabolites, mRNA expression changes and biological activity responses of components of antioxidant metabolism were examined in the heart tissues of all animals. The expression of cardiac gene markers increased by DOX exposure was significantly reduced by TA treatment, whereas mtDNA content, which was decreased by DOX exposure, was significantly increased. TA also improved antioxidant metabolism members' gene expression and enzymatic activity, including glutathione peroxidase, glutathione s‐transferase, superoxide dismutase, catalase, and thioredoxin reductase. This study provides a detailed overview of the current understanding of DOX‐induced cardiotoxicity and preventive or curative measures involving TA. [ABSTRACT FROM AUTHOR]

Testicular torsion is a common disorder in males and results in blockage of testicular circulation with subsequent damage of testicular germ cells. The current work aimed to compare the therapeutic effect of platelet-rich plasma (PRP) and injectable platelet-rich fibrin (i-PRF) on torsion/detorsion (T/D) injury in rats. Forty mature male Wister rats were arranged into 4 groups; (1) Control, (2) T/D, (3) T/D + PRP, and (4) T/D+ i-PRF. The right testis was twisting 1080° clockwise for 3 h in groups 2, 3 and 4, then 10 μl of PRP or i-PRF was injected intra-testicular 3 h after detorsion in groups 3 and 4, respectively. After 30 days postoperatively, the semen quality and hormonal assay were improved in PRP and i-PRF-treated groups with superiority of i-PRF (P < 0.001). High significance of Catalase, Glutathione Peroxidase (GPx), Superoxide Dismutase, Interleukin-1β (IL-1β), Caspase-3 and Tumor necrosis factor-α (TNF-α) was reported in treated rats with PRP and i-PRF (P < 0.001) with superiority to i-PRF-treated rats (P < 0.001). Testicular histoarchitectures were improved in PRP and i-PRF-treated rats with superiority of i-PRF-treated rats. It was concluded that PRP and i-PRF have regenerative efficacy on testicular damage after induced T/D injury with a superior efficacy of i-PRF. [ABSTRACT FROM AUTHOR]

Introduction: As effective growth-promoters and immune-modulators, yeast fermented products have shown positive effects in ruminants. To explore the mechanisms of yeast culture promoting growth and regulating immunity, this study investigated the effects of yeast culture, and β-glucan as one of its main active ingredients, on the growth performance, immune function, antioxidant capacity and hormonal profile in Mongolian ram lambs. Methods: One hundred and five Mongolian ram lambs were randomly assigned to 3 groups, with 35 replicates in each group. The dietary treatments were: total mixed ration (TMR) as the control group, TMR supplemented with 50-70 g/kg yeast culture (YC) or 75 mg/kg β-glucan. The test period was 137 days. All the sheep were weighed and 6 serum samples were collected in each group on days 0, 30, 60, 90 and 130, respectively. Results: The results showed that both YC and β-glucan could promote the growth performance with increased average daily gain and decreased feed to weight gain ratio. Moreover, these two feed additives facilitated the immune function by selectively increasing the serum levels of lysozyme, IgG, IgM, INF-γ, TNF-α and some interleukins (IL-1β, IL-2, IL-6 and IL-8); ameliorated the antioxidant capacity with higher total antioxidant capacity and enzyme activities of catalase and glutathione peroxidase; altered the metabolism-associated hormone levels with higher growth hormone and thyroid hormone T3 but lower cortisol and insulin. Discussion: In conclusion, both YC and β-glucan could improve the growth performance, immune function and antioxidant capacity, and regulate the serum levels of metabolism-associated hormones, thus exerting effects of promoting growth and improving immune function. Therefore, YC could be considered as a suitable potential alternative strategy to antibiotics and be used as an animal feed additive. This article provides a theoretical basis for the clinical application of such yeast fermented preparations in mutton sheep husbandry. [ABSTRACT FROM AUTHOR]

Large-mouth bass originally lived in rivers and lakes and now is often raised in recirculating aquaculture systems (RAS). However, the shortcoming of RAS is that there is very limited space for swimming fish in a high-density culture environment, thus leading to a lack of exercise. To investigate the effects of exercise training on growth performance, digestive enzymes, stress, and antioxidant capacity of large-mouth bass in a RAS, three training water flow velocities with three replicates were used in the present study: low water velocity: 0.5 body length per second (bl/s) (LV); medium water velocity: 1 bl/s (MV); and high water velocity: 1.5 bl/s (HV). 270 large-mouth bass (average initial body weight 47.51 ± 1.44 g, initial body length 12.71 ± 0.06 cm) were randomly divided into nine tanks (30 fish per tank). After 27 days experiment, the results showed that the growth performance of large-mouth bass, including feed intake, weight gain rate, and specific growth rate, in the HV group was significantly higher compared to the other groups. On the physiological level, the lipase and amylase activities were significantly increased in the HV group compared to the other groups. For the stress response parameters, the cortisol, glucose and lactate concentrations in the HV group were significantly increased, which may indicate higher stress in the HV group. Regarding the antioxidant enzyme activities, the activities of catalase (CAT) and glutathione peroxidase (GSH-PX) in the LV group were significantly higher than those in the HV group, which indicated that fish suffered higher oxidative stress in the LV group. Regarding the immune-related parameters, LZM and ACP activities had no significant differences among the groups, while AKP activities in the MV and HV groups were significantly higher than that in the LV group. Overall, the results demonstrated that exercise training had significant effects on the growth, digestion, stress, and immune response of large-mouth bass. It is suggested that exercise training with 1.5 bl/s can enhance fish growth, however, it also presents a potential risk of inducing stress in fish. Therefore, in rearing largemouth bass in RAS, the setting of water flow velocity should not only focus on the growth of large-mouth bass but also consider its welfare. [ABSTRACT FROM AUTHOR]

Introduction: Oral submucous fibrosis (OSMF) is a chronic, mild, possibly malignant condition (OPMD) that primarily affects South Asian people, affecting the oral cavity and oropharynx. Clinically, trismus, restricted tongue protrusion, burning mouth, marble-like oral mucosa appearance, xerostomia, recurrent ulceration, atrophy of the tongue papillae, and palpable fibrous bands are among the symptoms and indicators of OSMF. The present study was undertaken to determine the salivary levels of oxidative stress biomarkers malondialdehyde, 8-hydroxy-2-deoxyguanosine and 8-isoprostane levels and antioxidants glutathione peroxidase and superoxide dismutase in patients with different grades of OSMF. Methodology: The observational cross-sectional study was conducted in the department of Biochemistry NIMS&R, Jaipur in association with Oral Diagnosis and Radiology at College of Dental Sciences and Research Centre, Manipur, Ahmedabad (Gujarat) after obtaining institutional ethical committee clearance. The Study population consisted of Clinically diagnosed oral submucous fibrosis patients of age 18-45 years. Unstimulated Saliva was allowed to accumulate in the floor Of mouth and collected by drooling method in a test tube. Saliva samples will be stored at -20 °C until use. Malondialdehyde was estimated by thiobarbituric acid reaction using spectrophotometer, 8-hydroxy-2-deoxyguanosine was analysed by sandwich ELISA, Glutathione peroxidase and Superoxide dismutase were analysed by spectrophotometer and 8-Isoprostane was estimated by ELISA. Results: The present study included a total of 92 patients clinically diagnosed with oral submucosal fibrosis. It is seen that out of 92 patients, 53 were males and 39 were females accounting for 57.6% and 42.39% respectively. The mean age in years in males and females were 28.97±5.80 and 32.39±3.77 years respectively. The mean levels of oxidative stress markers were significantly increased and antioxidant levels were significantly decreased as OSMF advances. Pairwise comparison of mean values of salivary oxidative stress and antioxidant biomarkers were performed using post hoc analysis by Tukey test. Table 4 displays an almost highly significant (P<0.001) difference between the mean values of all the salivary biomarkers when compared pairwise. However, a significant difference (P=0.001) was found between Grade 2 vs Grade 3 for 8-Isoprostane. The mean difference between pair Grade 3 vs Grade 4 was found to be not significant for salivary Glutathione Peroxidise and salivary 8- isoprostane having P values of 0.52 and 0.41, respectively. Conclusion: The results of our study showed that the concentration of MDA, isoprostane, 8- Hydroxydeoxy-guanosine levels were increased significantly as the clinical stage and histopathological grade of OSMF advances suggesting these biomarkers can be used as a reliable biochemical marker and also a prognostic marker to assess the extent of oxidative damage in OSMF. The concentration of antioxidant enzymes showed progressive decline as OSMF advances, indicating the potential role of supplementation of antioxidants in these patients to decrease the progression of the disease. [ABSTRACT FROM AUTHOR]

Objectives: Previous studies have shown that gene expressions can be regulated in the hippocampus of rats after seizures induced by kainic acid (KA). The aim of this study was to examine the potential regulatory impact of KA administration on gene expression levels of enzymes responsible for drug metabolism in rat hippocampal tissue. Materials and Methods: Rats received intraperitoneal injections of KA and saline at a dose of 10 mg/kg. Behavioral changes were observed in experimental animals following the administration of KA. Four hours after receiving treatments, all rats were decapitated, and the brains were removed. Hippocampal tissues were used for total RNA isolation, and cDNA synthesis was performed by reverse transcription polymerase chain reaction (PCR). Gene expression levels of enzymes responsible for drug metabolism were determined by quantitative PCR using the RT2 Profiler PCR Array Rat Drug Metabolism PCR array system containing the relevant primers for a total of 84 genes. The gene expression levels of drug-metabolizing enzymes were quantified using the comparative Ct (2-ΔΔ(delta delta)Ct) method. The Student’s t-test was used for data analysis. Results: Our results indicate that KA treatment caused significant changes in the gene expression levels of metallothionein 3, glucose phosphate isomerase, adenosine triphosphate-binding cassette protein C1, cytochrome P450 enzymes (Cyp2c6v1, Cyp3a23/3a1, Cyp2c7), glutathione peroxidase 1, 4, and 5, glutamic acid decarboxylase 1 and 2, paraoxonase 2, carbohydrate sulfotransferase 1, glutathione S-transferases (Gsta3, Gstm1, Gstm4), microsomal glutathione S-transferase 3, carboxylesterase 2C, fatty acid amide hydrolase, pyruvate kinase-muscle, arachidonate 5-lipoxygenase, apolipoprotein E, cytochrome b5 reductase 5, xanthine dehydrogenase, N-acetyltransferase 1, glucokinase regulator, hexokinase 2, myristoylated alanine rich protein kinase C substrate, and stannin in the hippocampus compared with the control (p < 0.05). Conclusion: As a conclusion, it can be said that the seizure activity triggered by KA has the potential to change the gene expression levels of the enzymes responsible for drug metabolism in the hippocampus of rats. [ABSTRACT FROM AUTHOR]