Search Results (157)

Oxidative stress (OS) is increasingly recognized as a dynamic disturbance of cellular redox networks rather than a simple imbalance between oxidants and antioxidants. In this context, ferroptosis and cuproptosis—two regulated and metal-dependent forms of cell death—emerge as key mechanisms linking OS to metabolic dysfunction, inflammation, and tissue injury. This review integrates findings from biochemical, lipidomic and metallomic studies to describe how lipid peroxidation (LPO), glutathione (GSH)–Glutathione Peroxidase 4 (GPX4) activity, ferritinophagy, copper-induced mitochondrial protein lipoylation, and altered communication between organelles generate distinct redox signatures across diseases. By examining cutaneous, metabolic, cardiovascular, infectious, neurodegenerative, and oncologic conditions, we outline the shared redox pathways that connect iron- and copper-dependent cell death to systemic inflammation, immune dysregulation, and chronic tissue damage. Common oxidative markers—such as oxidized phospholipids, lipid aldehydes including 4-Hydroxynonenal (4-HNE) and malondialdehyde (MDA), and systemic metal imbalance—are highlighted as potential indicators of disease severity and as emerging therapeutic targets. We also discuss innovative analytical tools, including redox lipidomics, metallomic profiling and artificial-intelligence (AI)-based classification approaches, which improve the characterization of redox vulnerability and may guide the development of precision redox therapies. Overall, ferroptosis and cuproptosis represent unifying mechanisms that connect OS to multisystem disease and provide new opportunities for diagnostic refinement and targeted antioxidant-based interventions. Full article

Background: The senescence of testicular Leydig cells (LCs) is a key cause of age-related testosterone deficiency, in which oxidative stress (OS) and mitochondrial dysfunction are critical driving mechanisms. We explore whether the bioactive peptide C248 of PRDX4, an intracellular antioxidant, exerts mitochondrial protection to ameliorate LCs’ function. Methods: Based on the antioxidant domains of the PRDX4 protein, small molecular peptides were designed, and bioactive peptide C248 stood out from the crowd. An OS-induced senescence model of LCs was constructed by treating the MLTC-1 cell line with hydrogen peroxide (H₂O₂). C248 peptide or nicotinamide mononucleotide (NMN), as the positive control, was administered in the culture medium. The cellular function-related indicators, including DPPH free radical scavenging rate, cell viability, testosterone level, hydrogen peroxide (H₂O₂) content, senescence-associated β-galactosidase (SA-β-gal) activity, 8-hydroxy-2′-deoxyguanosine (8-OHDG) level, and 4-hydroxynonenal (4-HNE) level, were evaluated. The mitochondrial function and structural indicators, such as mitochondrial membrane potential, ATP production, mitochondrial morphology, and mitochondrial DNA (mtDNA) copy number, were subsequently tested. Results: In vitro experiments confirmed that C248 could scavenge DPPH free radicals in a dose-dependent manner, reduce the levels of reactive oxygen species, and increase antioxidant enzyme activity in LCs (p < 0.01). Both C248 and NMN increased testosterone secretion and improved cell viability (p < 0.01). Both C248 and NMN increased mitochondrial morphology and quantity, mitochondrial membrane potential (p < 0.01), ATP production (p < 0.01), and mitochondrial DNA (mtDNA) copy number (p < 0.01). Conclusion: This study reveals that the small molecular C248, a bioactive peptide of PRDX4, is a new candidate molecule for intervening in LC senescence and confirms that mitochondrial protection is a key strategy for improving age-related testicular dysfunction. Full article

Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus, driven by oxidative stress, inflammation, and microvascular dysfunction. Dapagliflozin, a selective inhibitor of sodium–glucose cotransporter type 2 (SGLT2), is used in the treatment of type 2 diabetes and has pleiotropic antioxidant and anti-inflammatory effects. The aim of this study was to evaluate the neuroprotective effects of dapagliflozin in an experimental model of streptozotocin (STZ)-induced diabetic peripheral neuropathy in mice. C57BL/6 mice were divided into three groups: control (DM–), STZ-induced diabetes (DM+), and diabetes + dapagliflozin (DM + DAPA, 10 mg/kg/day, oral administration for 12 weeks). Clinical (glycemia, weight, diuresis), electrophysiological, and histopathological parameters were evaluated, and behavioral tests (Open Field, Von Frey, Hot Tail) were performed. Dapagliflozin significantly reduced hyperglycemia, limited weight loss and polyuria, and improved locomotor behavior and nociceptive sensitivity. Electrodiagnostically, the treatment increased the amplitude and reduced the duration of motor potentials, indicating improved nerve conduction. Histological analyses showed decreased hydroxynonenal (HNE) immunoreactivity, suggesting attenuation of oxidative stress, reduced perineural fibrogenesis, and maintained intraepidermal nerve fiber density. Dapagliflozin exerts significant neuroprotective effects in experimental diabetic peripheral neuropathy by reducing oxidative stress, inflammation, and fibrosis and maintaining the structural and functional integrity of peripheral nerves. Full article

Cancer cell plasticity drives metastasis and therapy resistance through dynamic transitions between epithelial, mesenchymal, and neural crest stem-like (NCSC) states; however, a unifying mechanism that stabilizes these transitions remains undefined. To address this gap, we introduce a N-cadherin (CDH2)-centered redox–adhesion–exosome (RAX) hub that links oxidative signaling, adhesion dynamics, and exosome-mediated immune communication into a closed-loop framework. Within this network, reactive oxygen species (ROS) pulses license epithelial–mesenchymal transition (EMT), AXL–FAK/Src signaling consolidates mesenchymal adhesion, and selective exosomal cargoes—including miR-21, miR-200, miR-210, and PD-L1—propagate plasticity and immune evasion. Lipid peroxidation acts as a central checkpoint connecting ROS metabolism to PUFA membrane remodeling and ferroptosis vulnerability, buffered by NRF2–GPX4 and FSP1/DHODH axes, thereby converting transient oxidative pulses into persistent malignant states. Mechanistically, the RAX hub synthesizes findings from EMT/CSC biology, ferroptosis defenses, and exosome research into a self-reinforcing system that sustains tumor heterogeneity and stress resilience. Evidence from single-cell and spatial transcriptomics, intravital ROS imaging, and exosome cargo-selector studies supports the feasibility of this model. We further outline validation strategies employing HyPer–EMT–CDH2 tri-reporters, CRISPR perturbation of YBX1/ALIX cargo selectors, and spatial multi-omics in EMT-high tumors. Clinically, tumors enriched in EMT/NCSC programs—such as melanoma, neuroblastoma, small-cell lung cancer, pancreatic ductal adenocarcinoma, and triple-negative breast cancer (TNBC)—represent RAX-dependent contexts. These insights highlight biomarker-guided opportunities to target adhesion switches, ferroptosis defenses, and exosome biogenesis through lipid peroxidation-centered strategies using liquid-biopsy panels (exosomal CDH2, miR-200, miR-210) combined with organoid and xenograft models. By linking lipid peroxidation to ferroptosis defense and oxidative stress adaptation, the RAX hub aligns with the thematic focus of lipid metabolism and redox control in cancer progression. Collectively, the RAX framework may provide a conceptual basis for precision oncology by reframing metastasis and therapy resistance as emergent network properties. Full article

Cuban sugarcane wax alcohol (policosanol) is a blend of eight characteristic aliphatic alcohols extracted from the Cuban sugarcane and widely recognized for its multifunctional applications and therapeutic properties. In the present study, the potency of policosanol (POL) was assessed for its ability to prevent metabolic stress and associated disorders posed by a high-cholesterol (HC) and high-galactose (HG) diet in zebrafish (Danio rerio). Adult zebrafish (n = 56/group) were fed either with an HC+HG diet (containing 4%, w/w cholesterol and 30%, w/w galactose), or an HC+HG amalgamated diet with POL (final 0.1% w/w or 0.5% w/w). Zebrafish in the specified groups were sacrificed post-30 weeks of feeding, and blood and organs (liver, brain, and eyes) were processed for biochemical, histological, and immunohistochemical (IHC) analysis. After 30 weeks of feeding, the highest mortality (12.5%) was noticed in the HC+HG supplement group, which was reduced to 4.5% with co-supplementation of POL (0.1% and 0.5%). In a dose-dependent manner, POL significantly reversed HC+HG elevated levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), glucose, and malondialdehyde (MDA), while substantially augmenting plasma high-density lipoprotein cholesterol (HDL-C), sulfhydryl content, ferric ion reduction ability (FRA), and paraoxonase (PON) activity. In addition, POL mitigated HC+HG-induced hepatomegaly, inflammation, and fatty liver changes. Consistently, POL minimizes ROS generation and cellular senescence in the brain and substantially improves HC+HG-induced cognitive changes (cessation of swimming ability and motion), with a marked ~5 times higher swimming distance. Notably, POL mitigated the HC+HG-induced corneal opacity and attenuated oxidative stress, apoptosis, 4-hydroxynonenal (4-HNE) accumulation, and myelin sheath degeneration in the retina. The findings underscore the therapeutic potential of policosanol in attenuating oxidative stress, metabolic changes, and various organ damage caused by prolonged exposure to the HC+HG diet. Full article

Introduction: 5-HMF is a molecule found in carbohydrate-rich foods that is associated not only with cancer and anaphylactic reactions, but also with anti-oxidant properties. Questions arose as to whether 5-HMF exhibited a catalytic effect in relation to lipid peroxidation and lipoprotein oxidation in presence of metals and/or radicals. Methods: Peroxynitrite (ONOO⁻)-induced chemiluminescence and ONOO⁻ nitration of tyrosine residues on BSA using anti-nitro-tyrosine-antibodies were used to measure the protection of 5-HMF against peroxides or nitration compared to vitamin C (VitC). The reductive potential of 5-HMF or VitC on Cu²⁺ or Fe³ was estimated using the bicinchoninic acid (BCA) or Fenton-complex method. Human plasma was used to measure the generation of malondialdehyde (MDA), 4-hydroxynonenal (HNE), and total thiols after Fe²⁺/H₂O₂ oxidation in the presence of different concentrations of 5-HMF or VitC. Finally, Cu²⁺ oxidation of LDL after 4 h was carried out with 5-HMF or VitC, measuring the concentration of MDA in LDL with the thiobarbituric assay (TBARS). Results: VitC was 4-fold more effective than 5-HMF in scavenging ONOO⁻ to nearly 91.5% at 4 mM, with the exception of 0.16 mM, where the reduction of ONOO⁻ by VitC was 3.3-fold weaker compared to 0.16 mM 5-HMF. VitC or 5-HMF at a concentration of 6 mM inhibited the nitration of tyrosine residues on BSA to nearly 90% with a similar course. While 5-HMF reduced free Fe³⁺ in presence of phenanthroline, forming Fe²⁺ (phenantroleine)₃ [Fe²⁺(phe)₃] or complexed Cu²⁺(BCA)₄ to Cu⁺(BCA)₄ weakly, VitC was 7- to 19-fold effective in doing so over all the used concentrations (0–25 mM). A Fe²⁺—H₂O₂ solution mixed with human plasma showed a 6–10 times higher optical density (OD) of MDA or HNE in the presence of 5-HMF compared to VitC. The level of thiols was significantly decreased in the presence of higher VitC levels (1 mM: 198.4 ± 7.7 µM; 2 mM: 160.0 ± 13.4 µM) compared to equal 5-HMF amounts (2562 ± 7.8 µM or 242.4 ± 2.5 µM), whereas the usage of lower levels at 0.25 µM 5-HMF resulted in a significant decrease in thiols (272.4 ± 4.0 µM) compared to VitC (312.3 ± 19.7 µM). Both VitC and 5-HMF accelerated copper-mediated oxidation of LDL equally: while the TBARS levels from 4 h oxidized LDL reached 137.7 ± 12.3 nmol/mg, it was 1.7-fold higher using 6 mM VitC (259.9 ± 10.4 nmol/mg) or 6 mM 5-HMF (239.3 ± 10.2 nmol/mg). Conclusions: 5-HMF appeared to have more pro-oxidative potential compared to VitC by causing lipid peroxidation as well as protein oxidation. Full article

Prostate cancer is not only the most common type of cancer in elderly American men but also the 2nd leading cause of cancer death in American men. The currently available treatments in clinics target male hormones that are majorly required for maintaining many physiological functions, including muscle strength, leading to poor life quality and subsequent patient-opted intermittent treatment. Aging is a key factor in prostate cancer that is associated with increased levels of oxidative stress. Several lines of evidence indicated elevated levels of reactive oxygen species (ROS) in prostate cancer, including its precursor, prostate intraepithelial neoplasia (PIN). In this current study, we utilized 4-hydroxynonenal (4HNE) as a general readout for overall oxidative stress to demonstrate the imbalance between ROS and antioxidants in human prostate cancer and its precursor lesion in both human culture cell lines and tissue samples. Our results showed that the production of 4HNE adducts was increased in human prostate cancer cells and was non-linearly correlated with prostate cancer stage. They also provided insight into prevention and potential therapeutic strategies for prostate cancer. Full article

Dugongs (Dugong dugon), classified as vulnerable marine mammals, are increasingly impacted by infectious diseases, yet the role of septicemia and disseminated intravascular coagulation (DIC) in their mortality remains uncharacterized. This study aimed to investigate the pathological and microbiological features associated with an acute mortality event in a juvenile dugong during rehabilitation in southern Thailand. Comprehensive histopathological and microbiological analyses were conducted on tissue samples collected postmortem. Bacterial isolation and identification were performed using standard culture techniques and the VITEK-2 system. Histological examination revealed multisystemic lesions, including fibrin thrombi, hemorrhage, hepatocellular degeneration, pancreatic necrosis, lymphoid depletion, and neuronal damage. Oxidative stress and DNA damage were confirmed in brain tissues through immunofluorescence detection of 4-hydroxynonenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine (8-oxodG). Achromobacter xylosoxidans, an opportunistic pathogen, was isolated from multiple organs, consistent with acute systemic infection. These findings represent the first evidence of septicemia-associated DIC in dugongs caused by A. xylosoxidans, highlighting a previously undocumented cause of mortality in dugongs. The results emphasize the role of opportunistic bacteria in triggering oxidative damage and coagulopathy and underscore the importance of early detection and targeted therapeutic strategies to improve survival in stranded or rehabilitated dugongs. Full article

While omega-6 fatty acids play an important role in normal cell function, their excess in the diet is associated with an increased risk of developing diseases such as obesity, non-alcoholic fatty liver disease (NAFLD), inflammatory bowel disease (IBD) and Alzheimer’s disease. Furthermore, excessive intake has been shown to lead to chronic inflammation, which is related to increased production of reactive oxygen species (ROS). This conditioncan initiate lipid peroxidation in cell membranes, leading to the degradation of their fatty acids. One of the main products of omega-6 peroxidation is the α,β-unsaturated aldehyde, i.e., 4-hydroxynonenal (4-HNE), which is able to form four diastereoisomeric adducts with guanine. These 4-HNE adducts have been identified in the DNA of humans and rodents. Depending on their stereochemistry, they are able to influence double helix stability and cause DNA–DNA or DNA–Protein cross-links. Moreover, studies have shown that 4-HNE adducts formed in the human genome are considered mutation hotspots in hepatocellular carcinoma. Although the cell possesses defence mechanisms, without a well-balanced diet allowing correct cell function, they may not be sufficient to protect the genetic code. This review provides an overview of the molecular mechanisms underlying oxidative stress, lipid peroxidation, and the formation of DNA adducts. Particular emphasis is placed on the role of an omega-6-rich diet in inflammatory diseases, and on the formation of 4-HNE, which is a major product of lipid peroxidation, and its broader implications for genome stability, ageing, and disease progression. Full article

Introduction: Extrinsic skin damage is often a result of oxidative stress caused by exposure to environmental factors such as ultraviolet (UV) radiation, ozone (O₃), and various pollutants. As a result, topical antioxidants have been evaluated for their effectiveness in mitigating or reversing skin damage caused by environmental factors. Topical antioxidants containing a combination of l-ascorbic acid, tocopherol, and ferulic acid have significantly improved markers of skin health after exposure to environment-induced skin damage. However, research suggests that l-ascorbic acid and tocopherol tend to be relatively unstable, possibly affecting their efficacy against outdoor stressor damage. It has been shown that ferulic acid significantly improves the stability of both l-ascorbic acid and tocopherol, but its long-term stabilization effects on these antioxidants are relatively unknown. Material and Methods: This study evaluated the time-dependent effectiveness of a topical antioxidant mix containing 15% l-ascorbic acid, 1% tocopherol, and 0.5% ferulic acid (AOX) on UV-induced skin damage. Skin biopsies (12 mm, n = 60) were placed in a 6-well plate with medium and incubated at 37 °C and 5% CO₂ overnight. The day after, skin samples were pretreated with 10 µL of differently aged AOX (0-, 6-, 12-, and 36-month-old) and then exposed to different doses of UV light (100, 200, 400 mJ/cm²) daily over four days. AOX formulations were stored in a cool, dry, and dark place at approximately 20–22 °C during the whole study. This study evaluated 4-hydroxynonenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) as oxidative damage and skin DNA damage markers, Collagen1 and Filaggrin as skin structure, and IL-8 and Nrf2 as inflammatory and defensive response. Results: UV exposure significantly increased oxidative and inflammatory markers in human skin explants affecting also filaggrin and collagen levels. However, pre-treatment with the antioxidant formulation, particularly in its younger formulations (0-, 6-, and 12-month-old), significantly reduced the damaging effect of UV. Additionally, all antioxidant formulations effectively mitigated UV-induced damage across all doses. Conclusions: Our results indicate that pre-treatment with this formulation consistently reduces UV-induced oxidative damage and DNA damage in human skin explants, regardless of the formulation age and the discoloration state. Although effective, the protective capacity of aged formulations may be reduced only when extreme UV exposure is tested, a condition that is unlikely to occur under typical environmental conditions. These results support ferulic acid as a stabilization agent for topical antioxidant mixtures. Full article

Premature ovarian insufficiency (POI) is an important factor in female infertility and is often associated with oxidative stress. Alginate oligosaccharides (AOSs), derived from the degradation of alginate, have been demonstrated to have protective effects against various oxidative stress-related diseases. However, the impact of AOSs on POI has not been previously explored. The current study explored the effects of AOSs on ovarian dysfunction in a mouse model of POI induced by D-galactose (D-gal). Female C57BL/6 mice were randomly divided into five groups: the control (CON), POI model (D-gal), and low-, medium-, and high-dose AOS groups (AOS-L, 100 mg/kg/day; AOS-M, 150 mg/kg/day; AOS-H, 200 mg/kg/day). For 42 consecutive days, mice in the D-gal, AOS-L, AOS-M, and AOS-H groups received daily intraperitoneal injections of D-gal (200 mg/kg/day), whereas those in the CON group received equivalent volumes of sterile saline. Following D-gal injection, AOSs were administered via gavage at the specified doses; mice in the CON and D-gal groups received sterile saline instead. AOS treatment markedly improved estrous cycle irregularities, normalized serum hormone levels, reduced granulosa cell apoptosis, and increased follicle counts in POI mice. Moreover, AOSs significantly reduced ovarian oxidative stress and senescence in POI mice, as indicated by lower levels of malondialdehyde (MDA), higher activities of catalase (CAT) and superoxide dismutase (SOD), and decreased protein expression of 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), 8-hydroxydeoxyguanosine (8-OHdG), and p16 in ovarian tissue. Analysis of the gut microbiota through 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis revealed significant differences in gut microbiota composition and SCFA levels (acetic acid and total SCFAs) between control and D-gal-induced POI mice. These differences were largely alleviated by AOS treatment. AOSs changed the gut microbiota by increasing the abundance of Ligilactobacillus and decreasing the abundance of Clostridiales, Clostridiaceae, Marinifilaceae, and Clostridium_T. Additionally, AOSs mitigated the decline in acetic acid and total SCFA levels observed in POI mice. Notably, the total SCFA level was significantly correlated with the abundance of Ligilactobacillus, Marinifilaceae, and Clostridium_T. In conclusion, AOS intervention effectively mitigates ovarian oxidative stress, restores gut microbiota homeostasis, and regulates the microbiota–SCFA axis, collectively improving D-gal-induced POI. Therefore, AOSs represent a promising therapeutic strategy for POI management. Full article

Background: Accelerated demographic aging in Hungary and across Europe presents significant public health and socioeconomic challenges, particularly in preserving cognitive function and preventing neurodegenerative diseases. Modifiable lifestyle factors—especially dietary habits—play a critical role in brain aging and cognitive decline. Objective: This narrative review explores the mechanisms by which Western dietary patterns contribute to cognitive impairment and neurovascular aging, with specific attention to their relevance in the Hungarian context. It also outlines the rationale and design of the Semmelweis Study and its workplace-based health promotion program targeting lifestyle-related risk factors. Methods: A review of peer-reviewed literature was conducted focusing on Western diet, cognitive decline, cerebrovascular health, and dietary interventions. Emphasis was placed on mechanistic pathways involving systemic inflammation, oxidative stress, endothelial dysfunction, and decreased neurotrophic support. Key findings: Western dietary patterns—characterized by high intakes of saturated fats, refined sugars, ultra-processed foods, and linoleic acid—are associated with elevated levels of 4-hydroxynonenal (4-HNE), a lipid peroxidation product linked to neuronal injury and accelerated cognitive aging. In contrast, adherence to Mediterranean dietary patterns—particularly those rich in polyphenols from extra virgin olive oil and moderate red wine consumption—supports neurovascular integrity and promotes brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) activity. The concept of “cognitive frailty” is introduced as a modifiable, intermediate state between healthy aging and dementia. Application: The Semmelweis Study is a prospective cohort study involving employees of Semmelweis University aged ≥25 years, collecting longitudinal data on dietary, psychosocial, and metabolic determinants of aging. The Semmelweis–EUniWell Workplace Health Promotion Model translates these findings into practical interventions targeting diet, physical activity, and cardiovascular risk factors in the workplace setting. Conclusions: Improving our understanding of the diet–brain health relationship through population-specific longitudinal research is crucial for developing culturally tailored preventive strategies. The Semmelweis Study offers a scalable, evidence-based model for reducing cognitive decline and supporting healthy aging across diverse populations. Full article

The efficacy of Cuban sugarcane-extracted policosanol (Raydel^®), a purified blend of eight long-chain aliphatic alcohols, was compared to copycat sugarcane-extract powder (SCEP) to assess their effects on dyslipidemia, oxidative stress, and vital organs of zebrafish under the influence of a high-cholesterol diet (HCD). Zebrafish were fed with HCD (final 4%, w/w) or HCD infused with policosanol (PCO, final 1%, w/w) or SCEP (final 1%, w/w). Post 14-week consumption, blood and organs were harvested and processed for various biochemical, histological, and immunohistochemical (IHC) examinations, and fluorescent staining. Following 14-week consumption, the PCO-supplemented group exhibited higher zebrafish survival probability than the SCEP-supplemented group. Both PCO and SCEP substantially impacted the HCD-disrupted plasma lipid profile; however, PCO supplementation exhibited a significantly better effect than SCEP. Similarly, PCO supplementation significantly improved the blood glucose level, hepatic function biomarkers, and oxidative-antioxidant balance disturbed by HCD. PCO supplementation displayed a substantial inhibitory effect against HCD-induced fatty liver changes, nephromegaly, and cellular senescence. Likewise, PCO effectively protected the brain against HCD-induced apoptosis and accumulation of 4-hydroxynonenal (4-HNE); in contrast, SCEP supplementation showed almost no effect in reducing such adverse changes. The comparative findings between PCO and SCEP highlight the protective effects of PCO against HCD-induced oxidative stress and dyslipidemia via the enhancement of antioxidant markers, leading to protection of the liver, kidney, and brain, while SCEP failed to achieve similar outcomes. Full article

Lipid peroxidation (LPO) is a biochemical process through which lipids are subjected to a peroxidation reaction in the presence of free radicals. The process can cause alterations in biological membranes and the formation of substances harmful to the body that can form aggregates with proteins and nucleic acids. Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) are the main products of LPO. These compounds have cytotoxic and genotoxic properties and contribute to the pathogenesis of various diseases. This research focuses on the correlation between LPO and skin diseases. For some skin diseases, such as psoriasis, vitiligo, and alopecia, LPO products have been shown to have a clear role in the pathogenesis of the disease. Lipid aldehydic products like MDA and 4-HNE can enhance inflammation by stimulating pro-inflammatory genes and producing cytokines. Furthermore, these products can stimulate cell death and increase oxidative stress. For other diseases (atopic dermatitis, urticaria, pemphigus, and melanoma), the role of LPO is unclear, even if the levels of LPO biomarkers are elevated in proportion to the severity of the disease. LPO can also be exploited to counteract the proliferation of neoplastic cells. Therefore, enhancing LPO would play an adjuvant role in the therapy of neoplastic diseases such as melanoma. In particular, the therapeutic implication resulting from the role of LPO products in the cytotoxicity induced by photodynamic therapy used for the adjuvant treatment of melanoma could be of interest in the future. Full article

Alzheimer’s disease (AD) is characterized by amyloid-beta (Aβ) pathology and is closely linked to oxidative stress, which contributes to blood–brain barrier leakage, renal dysfunction, and cognitive decline. We investigated the effects of N-acetyl cysteine (NAC), an FDA-approved antioxidant, on oxidative stress, brain Aβ levels, barrier leakage, renal function, and cognition in 5xFAD mice. Eight-week-old 5xFAD mice were fed a rodent diet supplemented with 600 mg/kg_Diet NAC for 4 weeks; wild-type (WT) mice and control 5xFAD mice were fed a regular rodent diet. We detected elevated brain and renal 4-hydroxynonenal(4-HNE) levels, reduced creatinine clearance, and increased plasma S100β levels in untreated 5xFAD mice compared to WT controls. Untreated 5xFAD mice also had higher capillary leakage, reduced P-gp activity, and impaired cognition compared to WT. NAC treatment of 5xFAD mice reduced brain Aβ40 levels, normalized 4-HNE levels to control levels, improved creatinine clearance, decreased capillary leakage, and lowered S100β plasma levels. NAC improved cognitive performance in 5xFAD mice, as shown by Y-maze. Our findings indicate that Aβ-induced oxidative stress contributes to barrier dysfunction, renal impairment, and cognitive deficits in 5xFAD mice. Notably, NAC treatment mitigates these effects, suggesting its potential as an adjunct therapy for AD and other Aβ-related pathologies by reducing oxidative stress. Full article