Oxidative Stress Markers Research Articles

Introduction: Calcific aortic valve disease (CAVD) is a progressive condition that leads to aortic stenosis, heart failure, and premature death. Emerging evidence indicates that oxidative stress plays a significant role in the pathophysiology of CAVD by promoting damage to the endothelium lining the aortic valve. Our previous data provided evidence that sortilin orchestrates a complex intracellular signaling pathway culminating in endothelial dysfunction in mice through increased ROS production. Research Questions: To unveil the potential involvement of sortilin in the molecular mechanisms linking endothelial injury and oxidative stress in the progression of CAVD. Methods: Isolated human valve endothelial cells were used to identify the molecular mechanisms in vitro. Göttingen minipigs were randomly assigned to either a standard diet (SD) or a diet high in fat and cholesterol (HF) for 20 weeks. During this period, they received oral administration of either a placebo or the sortilin inhibitor AF38469. Blood samples were collected at baseline, during, and at the end of treatment for biochemical and oxidative stress marker analyses. Aortic cusps were analyzed histologically for cellularity, collagen, fibrosis, and calcification. Immunohistochemistry and Western blot assessed oxidative stress and osteoblast markers. Vascular reactivity studies evaluated endothelial function in isolated resistance vessels. Results: Immunohistochemistry revealed that the HF diet compromised endothelial integrity on the aortic valve surface, while sortilin inhibition preserved it. Furthermore, the HF diet group exhibited increased oxidative stress, activation of myofibroblast/osteoblast phenotypes, and mineralization in the valve, all of which were reduced by the sortilin inhibitor. Moreover, AF38469 significantly prevented the increased plasma cholesterol ( p< 0.0001) and triglyceride ( p< 0.0001) levels as well as the endothelial dysfunction observed in the placebo-treated HF diet group. Conclusions: Our data suggest that sortilin negatively regulates valvular degeneration by influencing the destruction of endothelial integrity, the increase in inflammation and oxidative stress, thereby highlighting its therapeutic potential in CAVD.

I ntroduction: Arterial stiffness and central arterial pressure are independent predictors of cardiovascular morbidity and mortality, with central pressure offering prognostic value beyond peripheral blood pressure (BP). While current guidelines recommend initiating treatment with single-pill combinations (SPCs), but the comparative effects of these combinations on arterial stiffness and central BP remain unclear, and no randomized evidence exists demonstrating their superiority, particularly in South Asian populations. This sub-study of the TOPSIN Trial aimed to evaluate the impact of three SPCs on aortic stiffness and central BP in Indian hypertensive patients. Methods: This is a triple-blind, randomized, three-arm trial involving 210 hypertensive patients aged 30–79 years. Participants were randomized in a 1:1:1 ratio to receive one of the following SPCs: amlodipine + perindopril (AM+PE), perindopril + indapamide (PE+ID), or amlodipine + indapamide (AM+ID). Eligible patients had clinic SBP≥140 and <160 mmHg on one antihypertensive or SBP ≥150 and <180 mmHg with no prior treatment. The study assessed central arterial stiffness- carotid-femoral pulse wave velocity (cf-PWV), carotid β-stiffness index (SI beta); carotid systolic (cSBP), diastolic (cDBP), and pulse pressure (cPP) using validated vascular analyzer (ArtSens-Plus, India). Secondary measures included 24-hour ambulatory BP (24ABPM), plasma nitric oxide concentration (NOx), and oxidative stress markers. SPCs were initiated at standard doses with forced up-titration at 2 months, and efficacy was assessed at 6 months. Results: Of the 210 randomized participants, 184 (38.0% women) aged 51±9.89 years were included in the final analysis. The mean 24h ambulatory SBP was 137.5±15.4 mmHg, and DBP was 85.3±9.1 mmHg. 53.3% had a history of hypertension, and 16.3% had diabetes. All three SPCs significantly reduced central and peripheral BP (p<0.001), but no significant between-group differences were observed. There were no significant changes in arterial stiffness. However, AM+PE and PE+ID combinations significantly improved NOx levels (p<0.01), while oxidative stress and antioxidant capacity remained unchanged across groups. Conclusion: All three single-pill combinations effectively reduced central and peripheral BP in Indian hypertensive patients, with no significant differences in arterial stiffness. Combinations containing perindopril improved nitric oxide levels, suggesting additional vascular benefits.

Introduction: Diabetic cardiomyopathy (DCM) is associated with the development of overt heart failure driven by complex, interdependent pathophysiological mechanisms. Although a self-perpetuating cycle of oxidative stress and inflammation is implicated in the development and progression of DCM, the precise underlying causal mechanisms remain unclear, with limited, largely nonspecific treatment options. Hypothesis: Regulating redox status in db/db mice using the MPO inhibitor and redox-modulating agent N-acetyl lysyltyrosylcysteine amide (KYC) improves heart function by shaping the immune response towards a more regulated state. Methods: After two weeks of habituation, 8-week-old male type 2 diabetic db/db mice were randomly assigned to daily treatment with KYC (subcutaneous, 10 mg/kg/d) or vehicle (PBS) for 12 weeks. Additionally, sex-matched 8-week-old C57BL/6J mice were used as a control. After treatment, left ventricular function was assessed with echocardiography. Left ventricle morphologies were evaluated with hematoxylin and eosin staining; the myocardial fibrosis content was quantified with Masson’s trichrome staining. The absolute counts of total lymphocytes, monocytes, and neutrophils in the peripheral blood were measured, and splenic T cells were determined with flow cytometry. Cardiac oxidative stress, inflammatory, and regulatory marker expression were evaluated by qPCR. Results: Treatment of db/db mice with KYC improved cardiac function and was associated with dampened systemic and cardiac inflammation. Histopathological studies of the hearts of db/db mice at 20 weeks of age revealed that KYC treatment decreased cardiomyocyte size and myocardial fibrosis. Importantly, splenic T cell characterization revealed that KYC treatment resulted in a significantly higher proportion of CD4+CD25+Foxp3+ (forkhead box P3) regulatory T cells (Tregs) and a lower ratio of both effector CD4 and CD8 T cells (Teffs) and Treg than the vehicle-treated diabetic mice. Cardiac transcriptomic analysis revealed that db/db mice exhibited an inflammatory profile, whereas those treated with KYC displayed regulatory and antioxidative defense pathways, including the Nrf2 pathway. Conclusions: KYC improved cardiac function by expanding CD4+CD25+FoxP3+ T regulatory cells (Tregs) and limiting oxidative stress and inflammation in db/db mice. These results suggest that targeting oxidative stress and inflammation has therapeutic potential for delaying cardiac dysfunction.

Skin aging is a prominent manifestation of human aging, largely driven by oxidative stress and inflammation. D-limonene, a natural monoterpene, possesses strong antioxidant and anti-inflammatory properties that may help counteract these effects. This study aimed to explore the anti-aging and skin-rejuvenating potential of D-limonene in a mouse model of D-galactose-induced skin aging. 60 male mice were divided into 6 groups (n = 10). Group I served as the control. Group II received D-galactose (500mg/kg) for 42days to induce aging. Groups III and IV received vitamin C (100mg/kg) either concurrently with D-galactose or after aging induction, respectively. Groups V and VI received D-limonene (100mg/kg) either simultaneously with D-galactose or after induction. This design allowed comparison of protective versus therapeutic effects. Both concurrent and post-treatment with D-limonene substantially decreased pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and the oxidative stress marker MDA, while enhancing antioxidant components (SOD and GPx) and promoting the synthesis of collagen types I and III. Additionally, it improved skin thickness and histomorphological scores, restoring normal skin architecture. D-limonene exerts potent anti-aging and skin-rejuvenating effects by modulating oxidation and inflammatory markers, suggesting its potential as a preventive and curative anti-aging agent.

Survivors of childhood acute lymphoblastic leukemia (ALL) frequently exhibit treatment-related neurocognitive impairment, although there is substantial interpatient variability in this outcome. Analysis of biomarkers that reflect the impact of chemotherapy during the two years of treatment for ALL offers the potential to identify children who have subclinical treatment-related neurotoxicity at a time when a protective intervention could prevent the development of persistent impairment. We prospectively measured markers indicative of oxidative stress (8-hydroxydeoxyguanosine) and neurodegeneration (total tau) in cerebrospinal fluid (CSF) collected at five timepoints before and during the first year of chemotherapy for ALL among 529 patients enrolled on Dana-Farber Cancer Institute ALL Consortium protocol 16-001 (NCT03020030). CSF 8-hydroxydeoxyguanosine and total tau change significantly over time, with parallel increases emerging during intensive phases of therapy, especially following repeated doses of intrathecal chemotherapy. A concordant increase in both markers was observed in 50% of patients; a concordant decrease was seen in a smaller subset (15%). In multivariable analysis, higher CSF tau was significantly associated with White race and non-Hispanic ethnicity. Analysis of CSF collected prospectively in a large cohort of children treated for ALL demonstrated significant changes in markers of oxidative stress and neurodegeneration within three months of treatment initiation. The clinical relevance of the putative biomarkers reported here will be validated by testing whether they are predictive of treatment-related cognitive decline. These biomarkers may then serve as surrogate markers for testing the efficacy of protective interventions designed to protect against treatment-induced neurotoxicity and cognitive decline.

Diabetes mellitus is largely driven by oxidative stress that disrupts insulin signaling, leading to failure in insulin-mediated glucose absorption. Exploration of natural bioactive compounds is fueled by their promising role in correcting redox imbalance. This study aims to investigate the antidiabetic effect of the methanolic extract of Praecitrullus fistulosus, potentially by transcriptional modulation in streptozotocin–nicotinamide-induced diabetic rats. Male Wistar albino rats (n = 36) were assigned to six groups: normal control; diabetic control; standard drug group; and three treatment groups receiving P. fistulosus extract orally at doses of 200, 400, and 600 mg/kg body weight, respectively, for 30 consecutive days. Diabetes was induced in all groups, except for normal control, by intraperitoneal co-administration of streptozotocin and nicotinamide. Nicotinamide (100 mg/kg) was injected 15 min prior to a single dose of streptozotocin (50 mg/kg). Baseline and endpoint assessments of weight and blood glucose levels were performed. Blood was processed to assess insulin-related indices, lipid profile, and oxidative stress markers. q-PCR and Western blotting were utilized to explore the underlying molecular mechanisms. The diabetic control-group rats exhibited impaired glucose tolerance due to the marked reduction in serum insulin levels, compromised β-cell function, and substantial rise in lipid profile and oxidative stress parameters. Oral administration of P. fistulosus methanolic extract effectively mitigated these alterations in a dose-dependent manner, accompanied by the upregulation of both gene and protein expression involved in the insulin-signaling cascade.

Epilepsy affects over 65million individuals worldwide, with approximately 30% of patients resistant to conventional antiepileptic drugs (AEDs). Neuroinflammation and oxidative stress are recognized contributors to epileptogenesis and seizure severity. Ammi visnaga (toothpick plant), traditionally used for its anti-inflammatory and antioxidant properties, remains understudied in the context of seizure-related neuroinflammation. This study aimed to investigate the neuroprotective, anticonvulsant, anti-inflammatory, and antioxidant properties of Ammi visnaga fruit hydroalcoholic extract in a pentylenetetrazole (PTZ)-induced seizure model in mice, with a particular focus on hippocampal oxidative stress and cytokine modulation. Forty adult male NMRI mice were randomized into Six groups including: both healthy negative control and PTZ + saline control, PTZ-only, phenobarbital-treated, and Ammi visnaga-treated (25, 50, and 100mg/kg). Seizure latency, hippocampal expression of IL-6 and TNF-α (via qPCR) and oxidative stress biomarkers (MDA, nitrite, TAC) were assessed. Seizure latency significantly increased with Ammi visnaga treatment in a dose-dependent manner (P < 0.0001), with the 100mg/kg group showing a robust delay compared to the PTZ group. Cytokine mRNA expression (IL-6 and TNF-α, measured by qPCR) were markedly downregulated in all extract-treated groups, reaching levels comparable to healthy controls (P < 0.001). Oxidative stress markers showed clear modulation; MDA and nitrite levels were significantly reduced in the hippocampus and serum at 100mg/kg (P < 0.01 and P < 0.05, respectively). Total antioxidant capacity (TAC) was substantially enhanced in both serum and hippocampal tissue, particularly in the 50 and 100mg/kg groups (P < 0.0001). In contrast, phenobarbital elevated seizure threshold but had minimal impact on oxidative stress biomarkers. Ammi visnaga fruit hydroalcoholic extract demonstrated potent, dose-dependent neuroprotective effects in a PTZ-induced seizure model through dual anti-inflammatory and antioxidative mechanisms. Its ability to suppress IL-6 and TNF-α expression and restore redox balance positions it as a promising adjunctive therapeutic candidate for epilepsy management, especially in drug-resistant cases driven by neuroinflammation and oxidative stress.

Inhalation exposure to nanoplastic particles (NPPs) can lead to significant pulmonary toxicity; however, the effects of environmental processing on their toxicity remain poorly understood. This study examines the toxicity of polystyrene (PS) NPPs on lung cells following controlled atmospheric aging. Human bronchial epithelial cells (16HBE) were cultured in vitro at the air-liquid interface and acutely exposed to oxidized PS NPPs through electrostatic precipitation. Expression of proinflammatory genes interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α) was significantly elevated at 6 and 48 h postexposure to aged NPPs, with corresponding increases in interleukin-6 (IL-6) protein levels supporting an inflammatory response. The oxidative stress marker heme oxygenase-1 (HO-1) also showed significantly increased expression at 6 h postexposure, supported by protein analysis. Atomic force microscopy (AFM) and aerosol mass spectrometry (AMS) revealed increased surface roughness and oxygen to carbon ratios in the atmospherically aged NPPs. Together, these results demonstrate that atmospheric aging alters the chemical composition and surface morphology of PS NPPs, enhancing proinflammatory and oxidative stress responses in bronchial epithelial cells, highlighting the critical role of environmental processing in determining the toxicity of nanoplastics.

BackgroundDiabetic cataract remains a prominent complication of diabetes mellitus, predominantly driven by oxidative stress and low-grade inflammation in the lens. Despite surgical remedies, efficacious pharmacological interventions to delay or prevent cataract progression are limited. L-tartaric acid, a naturally occurring dicarboxylic organic acid, exhibits notable antioxidative and anti-inflammatory properties, suggesting its potential therapeutic value in diabetic lens pathology.MethodsThis study explored the effects of L-tartaric acid on cataractogenesis in a streptozotocin (STZ)-induced diabetic rat model. Oral administration of L-tartaric acid (50 mg/kg/day) or vehicle commenced one-week post-diabetes induction and continued for 12 weeks. Cataract formation was evaluated via biomicroscopic scoring. Biochemical analyses of oxidative stress markers (malondialdehyde and antioxidant enzymes) and inflammation-related cytokines were conducted, alongside quantitative PCR to assess the expression of inflammation-related cytokines and transcription factors Nrf2 and NF-κB in lens tissues.ResultsChronic hyperglycemia significantly elevated oxidative damage and pro-inflammatory mediators in the lens, culminating in advanced cataract formation in untreated diabetic rats. In contrast, L‑tartaric acid treatment markedly reduced the incidence and severity of cataracts, lowering the proportion of lenses with advanced opacities (score ≥ 3) from 80 to 30%, a 62.5% relative reduction, concomitantly attenuating lipid peroxidation and improving antioxidant enzyme activities. Notably, L-tartaric acid suppressed pro-inflammatory cytokine expression and restored Nrf2 and NF-κB to near-normal levels, without altering blood glucose concentrations.ConclusionL‑tartaric acid significantly reduces oxidative damage and inflammation in the lens, and shows potential in protecting against diabetic cataract by reinforcing the endogenous antioxidant defense network and moderating inflammatory processes. These data suggest that L‑tartaric acid may serve as a promising adjunct therapy to curb the onset and progression of diabetic cataract, possibly through mechanisms independent of glycemic control. Further studies, including topical formulations and well-designed human clinical trials, are needed to validate these preliminary observations.

2,4-Dichlorophenoxyacetic acid (2,4-D) is a widely used herbicide, yet its potential to induce hepatorenal injury via oxidative stress and apoptosis raises significant health concerns. Lycium barbarum polysaccharides (LBP) possess recognized antioxidant and anti-apoptotic properties, but their protective mechanisms against 2,4-D toxicity, particularly through a multi-target network, remain inadequately explored. This study aimed to systematically investigate the mechanisms of 2,4-D-induced hepatorenal injury and the protective efficacy of LBP by integrating network toxicology, molecular docking, and experimental validation. An integrated approach was employed. Core targets and pathways were identified via network toxicology. Molecular docking predicted interactions between 2,4-D and these targets. In vivo validation was conducted on Sprague-Dawley rats treated with 2,4-D (75 mg/kg) and/or LBP (50 mg/kg) for 28 days, assessing histopathology, serum oxidative stress markers superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and cellular apoptosis (TUNEL staining). Network analysis identified PPARG, NFKB1, PPARA, NFE2L2, and SERPINE1 as core targets, with molecular docking confirming strong binding affinities (binding energies: −5.1 to −6.3 kcal·mol−1) and KEGG enrichment implicating cAMP, Ca2+, and PPAR signaling pathways. Experimentally, 2,4-D exposure induced significant histopathological damage, suppressed SOD/GSH-Px activities (p &lt; 0.001), elevated MDA levels (p &lt; 0.001), and markedly increased renal apoptosis (p &lt; 0.01). Crucially, LBP intervention substantially mitigated these alterations, ameliorating tissue injury, restoring antioxidant defenses, increasing SOD/GSH-Px (p &lt; 0.01), reducing MDA (p &lt; 0.001) and significantly decreasing renal apoptosis (p &lt; 0.05). This study elucidates a multi-target mechanism for 2,4-D-induced hepatorenal injury centered on oxidative stress–apoptosis dysregulation and demonstrates that LBP confers significant protection likely via modulation of this network. These findings underscore the potential of LBP as a natural protective agent against pesticide-induced organ damage and highlight the utility of integrated network approaches in toxicological research.

Clothianidin, a widely used neonicotinoid pesticide, poses potential ecological risks to aquatic ecosystems due to its unique mode of action and widespread environmental dispersal. This study investigates the toxic effects of clothianidin on Penaeus vannamei at different concentrations over 28 days. High concentrations of clothianidin significantly affected shrimp physiology, as evidenced by changes in survival rate and weight gain. Markers of oxidative stress, including decreased respiratory burst, reduced glutathione levels, and diminished antioxidant enzyme activities, indicated that clothianidin triggered oxidative stress responses in shrimp. Additionally, changes in lactate dehydrogenase, succinate dehydrogenase, and isocitrate dehydrogenase activities suggested disruptions in energy metabolism in the hepatopancreas. Analysis of the nervous system revealed significant disturbances in neural signaling, reflected by altered levels of acetylcholine, acetylcholinesterase, and dopamine. Transcriptomic analysis highlighted significant changes in gene expression and metabolic processes in the nervous system. This study demonstrates that clothianidin disrupts oxidative balance, energy metabolism, and neural signaling, affecting the growth of P. vannamei and providing valuable insights into its biochemical and transcriptomic toxicity in aquatic environments.Graphic Supplementary InformationThe online version contains supplementary material available at 10.1007/s44154-025-00259-0.

Background: Skeletal muscle is essential not only for structural integrity but also metabolic homeostasis. Muscle atrophy, the loss of muscle mass and function, is closely linked to chronic and metabolic disorders and is driven by chronic inflammation, oxidative stress, impaired myogenesis, and disrupted protein homeostasis. The present study aimed to evaluate the protective effects and underlying mechanisms of Rosa canina extract (RCE), a polyphenol-rich plant known for its antioxidant and anti-inflammatory properties, in vitro and in vivo models of muscle atrophy. Methods: We investigated the effects of RCE in TNF-α-treated L6 myotubes and a mouse model (eight-week-old male C57BL/6N) of immobilization-induced muscle atrophy. Markers of inflammation, oxidative stress, myogenesis, protein turnover, and anabolic signaling were analyzed via RT-PCR, Western blotting and ELISA. Muscle mass, performance, micro-CT imaging, and histological cross-sectional area were assessed in vivo. Results: RCE suppressed pro-inflammatory cytokines, restored antioxidant enzyme expression, and preserved myogenic markers. It inhibited muscle proteolysis by downregulating the genes involved in protein degradation and promoted protein synthesis by via activation of the PI3K/Akt/mTOR pathway. In mice, RCE mitigated muscle mass loss, preserved fiber cross-sectional area, improved strength and endurance, and restored muscle volume. Conclusions: RCE attenuated muscle atrophy by targeting inflammation, oxidative stress, proteolysis, and impaired anabolism. These findings highlight RCE as a promising natural therapeutic for preserving muscle health and metabolic homeostasis.

Quercetin attenuates busulfan-induced testicular and epididymal toxicity via modulation of oxidative stress, inflammatory cytokines, and apoptotic markers in rats.

A hypercaloric diet is associated with oxidative stress and the dysfunction of ATP-Binding Cassette transporter A1 (ABCA1), a key element in high-density lipoprotein (HDL) biogenesis and reverse cholesterol transport. Nicotinamide (NAM) presents antioxidant properties, which may contribute to maintaining lipid metabolism. Therefore, we aimed to evaluate the effect of NAM on HDL-cholesterol (HDL-C) level, oxidative stress markers, and the gene expression and protein levels of ABCA1 in Sprague-Dawley rats fed a hypercaloric diet. Forty male rats were divided into five groups: one group received a standard diet, and the remaining groups received a single high-fat, high-fructose diet (HFDF). Three of the HFDF groups received NAM treatment (5, 10, and 15 mM) in drinking water for 16 weeks (5 h/day). While HDL-C and oxidative stress were measured in serum samples, oxidative stress markers, and the gene expression and protein levels of ABCA1 were quantified in liver samples. The HDL-C level altered by the HFDF was improved by treatment with NAM. Furthermore, NAM reduces systemic lipid peroxidation levels and enhances the hepatic antioxidant response affected by the HFDF. In addition, NAM modulates the hepatic ABCA1 gene expression and protein level, altered by the HFDF. Our results suggest that NAM may modify the serum HDL-C level by an improvement of antioxidant response, and a possible modulation of the hepatic ABCA1 gene and protein expression. Further metabolic and molecular studies are needed to support the potential therapeutic role of NAM to prevent or treat lipid alterations promoted by a hypercaloric diet.

Azithromycin and Gallic acid alleviate neurobehavioral deficits in rats resulting from chronic Aflatoxin B1 exposure.

Modulation of TLR4-mediated inflammatory pathways and oxidative stress by cerium oxide nanoparticles in traumatic brain injury.

Interactive mechanism of elevated pCO2 and nutrient on 2-methylisoborneol production in cyanobacteria.

Ecotoxicological effects of cellulose acetate nanoplastic derived from cigarette butts on earthworm (Allolobophora caliginosa): Implications for soil health.

Effects of diet on sperm functionality and cryopreservation tolerance in Atlantic salmon (Salmo salar).

Assessing the toxicity of traffic-derived air pollution using a primary human air-liquid interface airway in vitro model.