Vitamin D mitigates cisplatin-mediated acute kidney injury through modulation of NRF2/HO-1 and autophagy signaling pathways.

Time-dependent renal protection by remote ischemic preconditioning through a hydrogen sulfide-mediated antioxidative and anti-inflammatory pathway.

Clozapine-Induced parotid inflammation and the effect of N-Acetyl cysteine on it: An experimental study.

Evaluation of oxidant stress markers in a population involved in a health care program.

Cardiovascular diseases are among the most common health problems worldwide. Inflammation plays a critical role in the pathogenesis of various heart diseases. Lipopolysaccharides (LPS) trigger inflammatory mechanisms, leading to an inflammatory response. Fluvoxamine (FLV) is a selective serotonin reuptake inhibitor with anti-inflammatory and antioxidative properties. This study investigated the potential protective effects of FLV on sepsis-induced cardiac inflammation and injury. Thirty-two female Wistar Albino rats were divided into four groups: control, LPS (5 mg·kg-1 intraperitoneally), LPS + FLV, and FLV (50 mg·kg-1·day-1 orally for 3days). Thirty minutes after the final FLV administration, LPS was administered, and animals were killed 6 h later. Cardiac tissues were evaluated by histopathological analysis, immunohistochemical assessment of caspase-3, TNF-α, interleukin-1 beta (IL-1β), interleukin-6 receptor (IL-6R), IL-10, and NF-κB; biochemical determination of total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI); and gene expression analysis by real-time quantitative polymerase chain reaction (RT-qPCR) of sirtuin-1 (SIRT-1), nuclear factor erythroid 2-related factor 2 (NRF-2), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and p53. LPS administration significantly increased TOS, OSI, caspase-3, TNF-α, IL-1β, IL-6R, NF-κB, and p53, while decreasing IL-10, SIRT-1, NRF-2, and PGC-1α, accompanied by marked inflammatory and structural cardiac damage. FLV treatment markedly reversed these alterations, attenuating inflammation, oxidative stress, and apoptosis. These findings suggest that FLV may confer cardioprotection against LPS-induced inflammatory and apoptotic cardiac injury, potentially through modulation of IL-6R/NF-κB-mediated inflammatory signalling and the SIRT-1-NRF-2-PGC-1α axis.

Theranekron Prevents Endotoxin-Induced Acute Kidney Injury by Modulating Inflammatory and Mitochondrial Apoptotic Pathways.

This study aimed to investigate oxidative stress (OS) markers and thiol-disulfide homeostasis (TDH) in patients with pseudoexfoliation (PEX) syndrome and to investigate their associations with ocular and systemic comorbidities. This case-control study included 89 participants, comprising 45 patients with PEX and 44 age- and sex-matched controls. Serum oxidative stress parameters, including total thiol (TT), native thiol (NT), disulfide, thiol-disulfide ratios, total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), were measured and compared between groups. The diagnostic utility of OS biomarkers was assessed through receiver operating characteristic curve (ROC) analysis. Additionally, the interrelationships among these biomarkers and their associations with ocular and systemic comorbid conditions observed in PEX were examined. TT and NT levels were significantly higher in PEX patients whereas disulfide, disulfide/TT, disulfide /NT and TAS were significantly lower. PEX patients revealed a 1.18‑fold increased risk of glaucoma with elevated disulfide and a 1.61‑times increased risk of hypertension with elevated disulfide levels. ROC evaluation demonstrated a high level of diagnostic capability: TT (AUC = 0.808, cut-off 416µmol/L, sensitivity 69%, specificity 86%), NT (AUC = 0.827, cut-off 377µmol/L, sensitivity 67%, specificity 91%), and disulfide (AUC = 0.681, cut-off 23.5µmol/L, sensitivity 80%, specificity 52%). Although our study shows that thiol-disulfide homeostasis appears to be significantly associated with glaucoma and hypertension in PEX patients, this relationship is not equally distributed across all comorbid conditions examined, and oxidative imbalance plays a more selective role in the disease burden associated with PEX.

Insulin resistance is a chronic, low-grade inflammatory condition and a central pathological feature of obesity and related conditions, including metabolic syndrome (MetS). Oxidative stress, inflammatory pathways, and dysregulation of adipokine secretion may contribute to its development. This study aimed to clarify these biological relationships using principal component analysis (PCA) in individuals with MetS. The study involved 190 adults diagnosed with MetS. Serum concentrations of metabolic and inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], and tumor necrosis factor-alpha [TNF-α]), oxidative stress indicators (glutathione peroxidase [GPx], superoxide dismutase [SOD], total antioxidant capacity [TAC], and total oxidant status [TOS]), and adipokines (omentin-1, adiponectin, visfatin, and leptin) were measured. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. PCA was conducted to investigate the associations between clusters of these biomarkers and HOMA-IR. Compared to individuals with HOMA-IR ≤ 2.5, those with HOMA-IR > 2.5 had significantly elevated serum triglycerides and TNF-α concentrations, as well as significantly lower levels of adiponectin, omentin-1, and TAC. PCA extracted 4 components explaining 59.45% of the total variance: lipid profile-related factor, oxidative stress-related factor, inflammatory-related factor, and adipokine profile factor. Of all 4 principal components, the inflammatory-related factor (i.e., hs-CRP and TNF-α) and the adipokine profile factor (i.e., leptin, adiponectin, and omentin-1) were independently associated with HOMA-IR > 2.5. Adipokine dysregulation, along with increased inflammation and oxidative stress, was associated with insulin resistance in MetS. PCA-derived biomarker clusters provide a mechanistic and integrative comprehension of metabolic risk stratification and may enable risk assessment and therapeutic strategies in the future.

Methotrexate (MTX), a widely used chemotherapeutic agent, is associated with central nervous system toxicity characterized by oxidative stress, neuroinflammation, and behavioral disturbances. The present study investigated whether curcumin mitigates MTX-induced neurotoxicity by modulating redox balance and inflammatory-neurotrophic signaling pathways. Twenty-four male BALB/c mice were randomly assigned to four groups: control, MTX (40 mg/kg, single intraperitoneal dose), MTX+curcumin (50 mg/kg oral pretreatment), and curcumin alone. Behavioral alterations were assessed using the open field, elevated plus maze, and tail suspension tests. Serum and hippocampal levels of tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were quantified. MTX administration induced significant anxiety- and depression-like behaviors, elevated TNF-α levels, increased TOS and OSI, and reduced TAS and BDNF in both serum and hippocampal tissue (respectively, p < 0.05 and p < 0.001). Curcumin pretreatment markedly attenuated these alterations, restoring redox homeostasis, suppressing TNF-α overexpression, and normalizing BDNF levels. Behavioral improvements paralleled biochemical recovery, particularly within hippocampal tissue. In conclusion, our data indicate that curcumin attenuates MTX-induced neurobehavioral deficits and biochemical alterations. The protective effects of curcumin are likely mediated, at least in part, by restoring redox homeostasis and modulating TNF-α/BDNF signaling, suggesting a potential therapeutic avenue for mitigating chemotherapy-induced neurotoxicity.

Background: Schizophrenia is a chronic neuropsychiatric disorder characterized by cognitive impairment, behavioral abnormalities, neuroinflammation, and oxidative stress. Increasing evidence suggests that dysregulated inflammatory cytokines and impaired antioxidant defenses contribute to schizophrenia pathophysiology. This study investigated the neuroprotective and anti-inflammatory effects of Gallic Acid (GA) in a ketamine-induced experimental schizophrenia model. Methods: Thirty male Balb/C mice were randomly divided into control, ketamine, and ketamine + GA groups. Schizophrenia was induced with ketamine (25 mg/kg/day) for 7 days, while the treatment group additionally received GA (60 mg/kg/day) for another 7 days. Behavioral tests, including open field, novel object recognition, and tail suspension tests, were performed to evaluate locomotor activity, cognition, and depressive-like behavior. Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-18 (IL-18), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant status (TAS), and total oxidant status (TOS) levels were analyzed in hippocampal and prefrontal cortex tissues to assess inflammatory and oxidative stress-related alterations. Results: Ketamine induced schizophrenia-like behaviors, including hyperlocomotion, memory impairment, and increased immobility. These behavioral alterations were accompanied by significantly elevated TNF-α, IL-1β, IL-18, and TOS levels, alongside reduced SOD, CAT, GSH-Px, and TAS levels in the hippocampus and prefrontal cortex. GA treatment ameliorated behavioral impairments, restored antioxidant enzymes, increased TAS levels, and reduced pro-inflammatory cytokines and TOS in these brain regions. Conclusions: GA exerted neuroprotective effects in the ketamine-induced schizophrenia model by reducing oxidative stress, neuroinflammation, and behavioral deficits. These findings suggest that Gallic Acid may serve as a promising therapeutic candidate for schizophrenia through modulation of inflammatory and oxidative stress pathways.

Although dietary glycemic index (GI) and glycemic load (GL) are known to affect inflammation and oxidative balance, their roles in OA are unclear. This study aims to investigate the relationship between dietary GI and GL with inflammation, oxidative stress, and clinical symptoms in patients with knee osteoarthritis (KOA). In a cross-sectional study, 160 patients diagnosed with KOA were included. Dietary intake was assessed using a validated food frequency questionnaire, and daily GI and GL values were calculated. Clinical symptoms were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Higher dietary GI and GL were significantly associated with increased serum levels of malondialdehyde (MDA), total oxidant status (TOS), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP), as well as with decreased total antioxidant capacity (TAC). Dietary GI and GL were positively correlated with the total WOMAC score, as well as with the WOMAC physical activity and stiffness. High dietary GI and GL may be associated with oxidative stress and inflammatory responses, and may worsen clinical symptoms in KOA patients. Nutritional strategies emphasizing low-GI/GL diets may contribute to better symptom control and disease management in KOA.

ABSTRACT Background Polycythemia vera (PV), the most common myeloproliferative neoplasm, is driven by JAK2 mutations and often coexists with metabolic syndrome (MS), a major cardiovascular risk factor. Few studies have examined oxidative stress as a potential link between PV and MS. Research design and methods This observational case–control study included 36 PV patients (15 with MS) and 40 healthy volunteers between 2017 and 2023. Diagnosis followed 2016 WHO criteria. Patients with abnormal hematologic values, organ dysfunction, elevated CRP, or confounding comorbidities were excluded. Oxidative stress was assessed by spectrophotometric measurement of total antioxidant status (TAS) and total oxidant status (TOS). Results TOS levels were significantly higher in PV–MS patients compared to PV alone (p < 0.05), and oxidative stress markers overall were elevated versus healthy controls (p < 0.05). No significant differences in TAS or TOS were observed between ELN high- and low-risk groups or among patients receiving hydroxyurea, aspirin, metformin, ACE inhibitors, and untreated patients (p > 0.05). Conclusions Oxidative stress is markedly elevated in PV patients with MS, supporting a pathophysiological link between the two conditions. These findings highlight the importance of considering oxidative stress in the clinical evaluation of PV patients with metabolic syndrome.

Synbiotics (combined probiotics + prebiotics) may ameliorate oxidative stress via gut microbiota-mediated mechanisms. However, previous syntheses were limited in biomarker scope and contaminated by retracted or compromised trials. This updated meta-analysis of randomized controlled trials (RCTs) aims to quantify the effects of synbiotic supplementation on a comprehensive panel of oxidative stress biomarkers in adults and to appraise the certainty of evidence. Following PRISMA guidance and a registered protocol, RCTs in adults comparing oral synbiotic supplementation (≥ 3 weeks) versus placebo were eligible. Primary outcomes were changes in malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), nitric oxide (NO), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione (GSH). Data were pooled using a random-effect model (standardized mean differences, SMD; 95% CI). Heterogeneity (I²), sensitivity, subgroup and publication-bias analyses were performed. Evidence certainty was rated with GRADE; studies formally retracted or with serious concerns were excluded. Eighteen RCTs were included. Synbiotic supplementation significantly reduced MDA (SMD: -0.87; 95% CI: -1.37, -0.37), TOS (SMD: -0.55; 95% CI: -1.03, -0.08) and OSI (SMD: -0.46; 95% CI: -0.78, -0.15). Antioxidant markers, including TAC (SMD: 0.25; 95% CI: 0.06, 0.43), SOD (SMD: 0.57; 95% CI: 0.13, 1.00), GSH (SMD: 0.70; 95% CI: 0.11, 1.28), and GPx (SMD: 1.40; 95% CI: 0.39, 2.40), were increased. GRADE ratings ranged from very low (MDA, GPx) to moderate (OSI). Synbiotic supplementation may improve certain oxidative stress biomarkers, including TAC, GSH, and MDA. However, findings for NO and OSI should be interpreted with caution due to the limited number of available studies and the low to very low certainty of evidence for some outcomes according to GRADE criteria. Further high-quality, large-scale RCTs are warranted to confirm these effects. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251103060.

ABSTRACTBackgroundMastitis is one of the most prevalent and economically significant diseases in dairy cattle, causing to inflammation of the mammary gland and reduced milk yield.ObjectivesThis study investigated the therapeutic efficacy of Vitex pseudo‐negundo (VPN) extracts in an experimentally induced rat mastitis model.MethodsSixty female Wistar rats were randomly assigned into six groups of 10. Group I served as the control group. Mastitis was induced by intramammary injection of Staphylococcus aureus (SA) (1.5 × 108 cfu/mL; 10 µL per gland) into the L4, L5, R4 and R5 mammary glands. Group III received intramammary gentamicin (0.25 mg/10 µL/day) for 5 days. Groups IV–VI received VPN extracts—water (0.2603 µg/kg/day), ethanol (0.0803 µg/kg/day) and petroleum ether (0.1042 µg/kg/day), administered at 10 µL per gland for the same duration. Rats were clinically monitored three times daily from the onset of clinical signs until euthanasia.ResultSA infection significantly increased mammary gland weight, total oxidative status (TOS) and bacterial load and induced tissue pathology, while decreasing total antioxidant status (TAS). C‐reactive protein levels remained unchanged. VPN significantly improved mammary gland weight, TOS, TAS, bacterial load and histological parameters (p < 0.001). Mammary gland weight, oxidative stress, bacterial load and histopathological lesion severity all decreased markedly following treatment. Histological examination showed near‐normal restoration of mammary gland architecture in all treatment groups.ConclusionPreparations of VPN, particularly the water extract, demonstrated strong potential for restoring altered microbiological, biochemical and histological parameters in this rat mastitis model.

Melatonin not only regulates circadian rhythms in animals but also supports reproductive health through its potent antioxidant properties and immunomodulatory effects. In this study, the effects of exogenous melatonin administration on blood total antioxidant status (TAS), total oxidant status (TOS), Immunoglobulin G (IgG), Immunoglobulin M (IgM), and prolactin (PRL) concentrations, as well as on pregnancy rates and litter size, were investigated in rabbits. A total of 26 New Zealand rabbits were divided into two groups for the study. Melatonin implants were administered subcutaneously (SC) to group 1 (n=13) (MEL). Saline injections were administered to group 2 (n=13) (CON). Samples were collected from all rabbits before mating, on the 15th day of gestation and after parturition from the ear marginal vein and TAS, TOS, IgG, IgM, PRL concentrations and hemogram parameters were analyzed. Pregnancy rates were 77% and 92.3% in the CON and MEL groups, respectively, while litter sizes were 5.2 and 6 in the CON and MEL groups, respectively. TOS levels were found to be statistically lower (p<0.05) in the MEL group compared to the CON group just after parturition; however, there was no statistical difference between the groups in terms of TAS values at different times (p>0.05). IgG and IgM levels before mating and after parturition did not differ statistically significantly between the experimental groups when melatonin was administered. However, a statistically significant increase in the levels of both IgG and IgM was observed in the MEL group on day 15 of gestation. Exogenous melatonin administration did not alter reproductive parameters in New Zealand rabbits; however, it exhibited immunomodulatory effects on the 15th day of gestation and reduced oxidative stress after parturition.

Metformin attenuates neurodegeneration in ICV-STZ-induced Alzheimer's model via antioxidant and anti-inflammatory mechanisms: implications for disease-modifying therapy.

Epirubicin (EPI) can cause metabolic side effects, including chemotherapy-related diabetes, partly through oxidative stress that disrupts zinc (Zn) homeostasis and impairs autophagy. This study investigated the effects of EPI on Zn regulation and autophagy in the pancreas, as well as the modulatory role of N-acetylcysteine (NAC). Rats received EPI (9.6 mg/kg) by intraperitoneal injection (i.p.) followed 1 h later by NAC (50 or 300 mg/kg, i.p.). Glucose homeostasis was assessed using the Homeostatic Model Assessment (HOMA-IR), and β-cell function was assessed using HOMA-β levels. Plasma insulin levels, as well as insulin, proinsulin, beclin, autophagy-related proteins (ATG5), Microtubule-Associated Protein 1 Light Chain 3 (LC3), phosphorylated Akt (p-Akt), mechanistic target of rapamycin complex 1 (mTOR1), cleaved caspase-3, Zrt/Irt-like Protein 10 (ZIP10), and the proliferation marker Ki-67 in pancreatic tissue, were measured using commercial ELISA kits. Total oxidant status (TOS) and total antioxidant status (TAS) were measured using commercial colorimetric assay kits, and the oxidative stress index (OSI) was calculated. Zn levels in pancreatic tissue and plasma samples were measured using a colorimetric method. Morphological changes in the pancreas were assessed by hematoxylin and eosin staining. As a result, in the EPI group, oxidative stress and ZIP10 levels increased, whereas Zn levels decreased, as well as pancreatic autophagy, proliferation, and insulin synthesis increased. Oxidative stress decreased in both the EN-50 and EN-300 groups, with a more pronounced decrease in the EN-300 group. Furthermore, in the EN-300 group, pancreatic Zn, ZIP10, autophagy, and proliferation levels decreased, whereas mTOR1 levels increased. The pancreatic insulin synthesis observed in the EN-50 group was not observed in the EN-300 group. In conclusion, the increased autophagy observed in the Epi group may reflect an adaptive response to oxidative stress. The effects of NAC on oxidative stress may be dose-dependent, and high-dose NAC administration may suppress EPI-induced autophagy via mTOR1-mediated signaling. Furthermore, the relationship among Zn levels, autophagy, and insulin synthesis observed in the experimental groups may contribute to a better understanding of EPI-associated diabetogenic alterations.

Alzheimer's disease (AD) lacks effective early-stage non-pharmacological interventions capable of simultaneously targeting neurotrophic signaling and neurofunctional decline. This study examined the early-stage effects of tactile stimulation (TS), aerobic exercise (Ex), and their combination (TS + Ex) on behavioral, molecular, and histopathological outcomes in 5xFAD mouse model of AD. Twenty-eight male transgenic 5xFAD mice (7-8 weeks old) were randomly assigned to four groups: control (n = 7), TS (n = 7), Ex (n = 7), and TS + Ex (n = 7). Interventions were applied for eight weeks, 5 days per week, with daily 30-minute sessions. Behavioral assessments were conducted, and biochemical analyses measured brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), fibroblast growth factor-2 (FGF-2), irisin, lactate, total antioxidant status (TAS), total oxidant status (TOS), and myeloperoxidase (MPO) levels in brain, muscle, skin, and serum tissues. Histological, immunofluorescent, and ultrastructural evaluations were performed in the hippocampus. Compared to control, the TS + Ex group showed significant improvements in motor performance, neurotrophic factor levels, irisin and lactate concentrations, and antioxidant capacity in 5xFAD mice (p = 0.05-<0.001, partial η²=0.498-0.902). Additionally, increased doublecortin expression (p = 0.032, partial η²=0.571) and improved histopathological architecture were observed. Aerobic exercise alone improved motor function, anxiety-related behaviors, modulated several biochemical and histological outcomes compared with the control (p = 0.05 - 0.004, partial η²=0.332-0.498). TS alone produced limited effects, with notable increases only in hippocampal BDNF (p < 0.001, partial η²=0.712) and lactate levels (p = 0.015, partial η²=0.605) compared with the control group. The combination of TS and Ex may exert synergistic neuroprotective effects, suggesting that multimodal non-pharmacological strategies could represent promising early-stage interventions for mitigating AD-related pathology.

Contrast agents are widely used in medical imaging to improve tissue differentiation, but they can cause serious inflammatory responses, including contrast-induced nephropathy (CIN). Dexpanthenol (DEX) is known for its antioxidant, anti-inflammatory, and anti-apoptotic properties. This study aimed to investigate the potential protective effects of dexpanthenol in a rat model of diatrizoate-induced CIN. In this study, 32 Wistar albino rats were randomly divided into four groups: control, Urografin (URO; 10mL/kg, intraperitoneal [i.p.]), URO + DEX (500mg/kg, i.p. for 3days), and DEX alone. Renal function markers (serum urea and creatinine), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were measured. Histopathological evaluation and immunohistochemical analysis of tumor necrosis factor-alpha (TNF-α) and caspase-3 (Cas-3) were performed. Additionally, SIRT1, Bcl-2, Bax, and p53 mRNA expression levels were assessed. URO administration increased TOS and OSI values and caused significant renal histopathological damage. TNF-α and Cas-3 immunoreactivity, along with Bax and p53 gene expression, were significantly elevated, while Bcl-2 and SIRT1 expression was suppressed. DEX treatment provided partial improvement in these changes, contributed to the preservation of renal architecture, and was associated with improvements in biochemical and molecular parameters approaching those of the control levels. In conclusion, DEX may exert nephroprotective effects against CIN by reducing oxidative stress, inhibiting pro-inflammatory and apoptotic pathways, and increasing anti-apoptotic gene expression. These findings provide a preclinical basis supporting the idea that dexpanthenol is a promising candidate for further translational and clinical studies in contrast-induced renal injury.

Molecular and structural abnormalities triggered by oxidative stress are key determinants of diabetes pathophysiology, and research into natural therapeutic agents targeting these mechanisms is gaining speed. This study aimed to evaluate the effects of Artemisia haussknechtii leaves ethanolic lyophilized and nanoparticle extract forms on glycemic regulation, oxidative stress markers, and tissue integrity in an experimental diabetes model. A total of 48 female rats were divided into six groups; diabetes was induced with 45mg/kg STZ (i.p.). DYEE and DYNE were administered orally at doses of 50 and 100mg/kg for 21 days. Weekly fasting glucose and body weight were monitored. At the end of the study, serum biochemistry, erythrocyte and tissue oxidative stress markers (MDA, GSH, CAT, GPx, SOD, GR, TAS, TOS) were analyzed; liver, kidney, and pancreas tissues were evaluated histopathologically. Diabetic rats exhibited persistent hyperglycemia, body weight loss, dyslipidemia, elevated liver and kidney injury biomarkers, increased lipid peroxidation (MDA), and total oxidant status (TOS), accompanied by marked suppression of antioxidant defense systems. Treatment with Artemisia haussknechtii extracts significantly ameliorated these alterations in a dose-dependent manner. Notably, the high-dose nanoparticle formulation (DYNE2) produced the most pronounced improvements, reflected by reduced blood glucose levels, improved lipid profile, normalization of insulin, HbA1c and c-peptide levels, decreased MDA and TOS, and restoration of antioxidant parameters toward control values. Histopathological findings corroborated the biochemical data, demonstrating substantial attenuation of diabetes-induced tissue damage, particularly in the DYNE2 group. Artemisia haussknechtii extract, particularly in its nanoparticle form, has demonstrated antihyperglycemic, antioxidant, and tissue-protective effects in experimental diabetes. The findings suggest that the plant is a promising candidate for complementary treatment against diabetes-related oxidative stress and organ damage.