Search Results (173)

Carnosine (CAR), an endogenous histidine-containing dipeptide, exhibits antioxidant and anti-inflammatory activity in various experimental models; however, its molecular mechanism of action remains poorly understood. Here, we demonstrate that the Michael adduct between CAR and 4-hydroxy-2-nonenal (HNE), which has been detected in previous studies in both in vitro and in vivo settings, mediates its bioactivity, particularly its antioxidant and anti-inflammatory responses, through Nrf2 activation. The CAR–HNE adduct was synthesized and its physicochemical, metabolic, and biological properties were evaluated. CAR–HNE exhibited high stability in biological matrices and retained the ability to transfer HNE to thiol nucleophiles at a slow rate under physiologically relevant conditions, consistent with electrophile-mediated Nrf2 activation. This kinetic behavior limits the cytotoxicity typically associated with free HNE while preserving the redox signaling capacity. CAR–HNE induced dose-dependent Nrf2 activation and NF-κB inhibition in cell-based assays without the hormetic toxicity observed for free HNE. Mechanistically, CAR–HNE may act as a redox-tunable electrophilic reservoir, restoring nucleophilic tone and modulating redox-sensitive transcription factors. In vivo, CAR–HNE attenuated DSS-induced colitis more effectively than equimolar doses of either carnosine or HNE alone. Proteomic analyses revealed modulation of canonical Nrf2-dependent antioxidant pathways. Our findings suggest a conceptual shift in carnosine biology: rather than acting as a classical antioxidant or carbonyl quencher, carnosine functions as a precursor of redox-active electrophilic adducts that transduce anti-inflammatory and antioxidant responses via controlled RCS signaling. Full article

Ionizing radiation has been an important tool in medical diagnosis and treatment. While the use of radiation for diagnostic purposes has been successful, clinicians are wary of the possible negative effects radiation may have on the patient. According to the linear no-threshold model, all levels of radiation are considered harmful and there is no safe threshold. However, some studies suggest there may instead be a hormetic response at lower doses typically defined as exposure below 100 mGy, and that low doses may be beneficial as a possible immunomodulatory therapeutic. Therefore, it is increasingly important to understand the effects of exposure to low doses of radiation. The lung is frequently exposed to radiation from both environmental and medical sources. The effects of low doses of radon, the most heavily studied public radiation exposure source, are still contested, as well as the potential risk from medical X-ray imaging and computed tomography exposures during diagnostic procedures. In order to appropriately evaluate the potential risks and benefits of a low-dose exposure, it is necessary to understand the mechanism(s) of action, particularly the role of DNA damage, reactive oxygen species, inflammation and immune response. Here, we review the mechanistic evidence of low-dose radiation exposure effects on the lung in the current literature and discuss the implications of these results on the validity of the LNT model as well as potential hormetic or adaptive responses. Full article

Ketoprofen is a widely prescribed non-steroidal anti-inflammatory drug whose extensive global use, combined with limited biodegradability, has led to its increasing detection as a micropollutant in aquatic and terrestrial environments. Incomplete removal during wastewater treatment results in its continuous release into surface waters and soils, creating conditions for chronic, low-dose exposure of non-target organisms. This review synthesizes current knowledge on the physicochemical characteristics of ketoprofen, its mechanism of action, environmental occurrence, degradation pathways, and ecotoxicological effects. Particular emphasis is placed on biological and photochemical transformation processes that influence ketoprofen persistence and toxicity. While the acute toxicity of ketoprofen has been relatively well documented, data on chronic toxicity remain scarce, despite growing evidence that long-term exposure may pose significant ecological risks. Studies indicate that low environmental concentrations can induce hormetic responses in animals and plants, whereas higher levels may cause cellular damage associated with oxidative stress, affecting organisms ranging from microorganisms to vertebrates and vascular plants. By integrating available data on ketoprofen degradation and toxicity, this review highlights critical knowledge gaps regarding its chronic ecotoxicity and underscores the need for systematic environmental monitoring and the development of effective degradation strategies to mitigate risks to non-target organisms. Full article

The search for new growth-regulating compounds remains a relevant research direction in view of the issue of food security. Previously, a number of thiazolyl acetic acid derivatives have been synthesized, which are promising biologically active compounds according to their physicochemical characteristics. The aim of this work was to study the growth-regulating properties of both previously and newly synthesized thiazolyl acetic acid derivatives using a growth phytotest with Lepidium sativum and Sinapis alba. This study was carried out under laboratory conditions of phytotesting growth indicators of test plants of the class Dicotyledones—L. sativum and S. alba under the influence of 10 μg/mL, 100 μg/mL, and 1000 μg/mL aqueous solutions of the compounds with a comparative analysis of the action of the active components of Rhizopon^TM and herbicide benazolin. It was found that, exhibiting high herbicidal properties at a concentration of 1000 μg/mL (primarily the compound with a benzothiazole fragment), the studied thiazolyl acetic acid derivatives with decreasing concentration (100 μg/mL and 10 μg/mL) reduce phytotoxicity to its complete elimination against L. sativum and S. alba for the compound 2-[2-(N-tert-butoxycarbonyl)-aminoethyl-1,3thiazol-4-yl]acetic acid (compound 3), as well as against L. sativum for the compound 5-phenylthiazol-2-yl acetic acid (compound 5). A weak stimulating effect on the length of the above-ground part of S. alba seedlings was recorded for 2-[2-(3,3,3-trifluoropropyl)-1,3thiazol-4-yl]acetic acid (compound 1) and 2-[2-(N-tert-butoxycarbonyl)-aminoethyl-1,3thiazol-4-yl]acetic acid (compound 3) at their concentration of 10 μg/mL; however, an improvement in the vitality index under the action of these compounds was not observed. The results obtained in this study indicate the biological activity of both previously and newly synthesized thiazolyl acetic acid derivatives, namely their growth-regulatory properties, expanding knowledge about promising herbicidal compounds with a possible hormetic effect, which requires further research. Full article

Background/Objectives: Tributyltin (TBT) remains a persistent aquatic contaminant with documented neurotoxic effects, yet the underlying mechanisms of its neurotoxicity remain poorly understood. Methods: We investigated the comprehensive molecular mechanisms of TBT-induced neurotoxicity in zebrafish (Danio rerio) through an integrated approach combining histopathological examination, metabolomics analysis, transcriptional profiling, and behavioral assays. Results: Histopathological analysis revealed significant TBT-induced damage to brain tissue architecture. Metabolomic profiling demonstrated that TBT exposure (500 ng/L) severely disrupted cellular energy metabolism, particularly the TCA cycle and purine/pyrimidine metabolism, while exhibiting hormetic responses at lower concentrations. Transcriptional analysis identified widespread downregulation of SNARE complex proteins and neurotransmitter transporters, indicating comprehensive deterioration of synaptic machinery. Conclusions: These molecular perturbations corresponded with systematic disruption of antioxidant defense mechanisms and neurotransmitter signaling pathways, establishing a direct mechanistic link to observed behavioral deficits. Our findings reveal a hierarchical cascade of molecular disruptions triggered by TBT exposure, bridging the critical gap between metabolic dysregulation and synaptic dysfunction. This mechanistic framework provides fundamental insights into the neurotoxicological impact of this widespread environmental contaminant, highlighting potential therapeutic targets for intervention. Full article

Recent evidence has highlighted the pivotal roles of reactive oxygen species (ROS) and the SIRT1, AMPK, and mTOR signaling pathways in aging and longevity, making them attractive targets for studies of lifespan-extending interventions. We previously demonstrated that 1,1-diethoxyethane (1,1-DEE) could interact with mitochondrial complex I (NADH–ubiquinone oxidoreductase), leading to transient mitochondrial ROS (mtROS) production and activation of the AMPK pathway. This study further examined the effects of 1,1-DEE on longevity in model organisms. Treatment with 1,1-DEE decreased senescence in endothelial cell EA.hy926. In Caenorhabditis elegans (C. elegans), 1,1-DEE induced a hormetic response and extended the lifespan, whereas its structural isoform, 1,2-diethoxyethane (1,2-DEE), showed no such effect. In rat models, administration of 1,1-DEE markedly improved survival rate, mortality risk, restricted mean survival time (RMST), and median lifespan, associated with an accelerated body weight reduction. Additionally, 1,1-DEE could also enhance learning and memory, as assessed by the Morris water maze test in rats. These findings suggest that 1,1-DEE may serve as a novel small-molecule modulator of mitochondrial function and redox signaling, with potentials for promoting anti-aging and longevity. Full article

Pre-sowing seed treatment (priming) is a strategic tool for programming future crop yield, aimed at improving early plant development and enhancing stress resilience. This study investigated the effects of priming wheat seeds with 100 µM ibuprofen on early ontogeny under optimal conditions and salt stress (100 mM NaCl). An evaluation of germination energy, growth parameters, phytohormone levels (abscisic acid, indolylacetic acid, and cytokinins) and the status of the antioxidant system in 7-day-old seedlings demonstrated that ibuprofen treatment stimulates wheat growth and tolerance, despite its absence of accumulation in plant tissues. Modulation of hormonal balance plays a key role in these protective effects: under optimal conditions, ibuprofen elevates abscisic acid and indolylacetic acid levels, while under salt stress, it prevents excessive abscisic acid accumulation and mitigates the stress-induced decline in indolylacetic acid and cytokinins. Furthermore, ibuprofen promotes a coordinated increase in glutathione, ascorbate, and H₂O₂ levels, concomitant with the activation of key enzymes (glutathione reductase and ascorbate peroxidase), thereby enhancing the plants’ antioxidant potential. Under saline conditions, ibuprofen pretreatment also reduces stress-induced dysregulation of this system. Therefore, ibuprofen acts as a hormetic preconditioning agent that improves seedling vigor and stress tolerance by fine-tuning hormonal signaling and redox metabolism. Full article

4-hydroxy-TEMPO is a water-soluble nitroxide radical with potent antioxidant and redox-modulating properties. Its small molecular weight and membrane permeability enable it to act as a superoxide dismutase mimetic, efficiently scavenging reactive oxygen species and mitigating oxidative damage. In this study, we investigated the physiological and transcriptomic effects of 4-hydroxy-TEMPO in Saccharomyces cerevisiae, using wild-type and mutant strains deficient in key redox and DNA repair pathways (sod1Δ, sod2Δ, yap1Δ, rad52Δ). RNA-Seq analysis revealed widespread transcriptional reprogramming. Treatment with 4-hydroxy-TEMPO impaired cell growth, induced accumulation of cells with 1C (G1 phase) DNA content, and modulated chronological aging in a strain-dependent manner. Notably, low concentrations delayed aging in wild-type, yap1Δ, and rad52Δ strains, while accelerating it in sod1Δ mutants, consistent with a hormetic response. Unlike TEMPO, 4-hydroxy-TEMPO exhibited markedly reduced translational toxicity, preserved polysome structure at high doses, and triggered a non-canonical, redox-dependent transcriptional program characterized by induction of stress-response genes together with unexpected up-regulation of multiple ribosomal protein genes. This was accompanied by a biphasic, genotype-specific hormetic response and a measurable genoprotective effect. RT-qPCR confirmed key transcriptional changes, linking transcriptome remodeling to functional outcomes. Full article

This research aimed to assess the effect of chitosan nanoparticles (ChNPs) during in vitro shoot proliferation of vanilla using temporary immersion bioreactors (TIB). TIB culture is a biotechnological process that uses semiautomated containers for the production of explants exposed in liquid culture medium. Concentrations of control, 25, 50, 100, 200, and 400 mg/L ChNPs were evaluated in Murashige and Skoog culture medium. Morphological characterization of ChNPs was performed using scanning electron microscopy. At 60 days of culture, survival (%), development variables, photosynthetic pigment content, lipid peroxidation expressed in malondialdehyde, total phenolic content (TPC), hydrogen peroxide (H₂O₂) content, and total antioxidant capacity (TAC) expressed in trolox equivalents were evaluated. The data were analyzed with analysis of variance, with a Tukey test (p ≤ 0.05) using SPSS statistics software, version 29. The results revealed that the greatest survival (%) was obtained at concentrations of control, 25, and 50 mg/L ChNPs, while the lowest survival (%) was observed at concentrations of 400 mg/L ChNPs. Growth stimulation was found, as well as an increase in chlorophyll and β-carotene at concentrations of 25 and 50 mg/L ChNPs. The level of H₂O₂ increased at 25 and 50 mg/L ChNPs. Lipid peroxidation showed no differences among treatments. TPC increased at 100 and 200 mg/L ChNPs, while TAC increased at 200 and 400 mg/L ChNPs. In conclusion, the administration of ChNPs at low concentrations can stimulate growth, while at high concentrations they can inhibit it, a response known as hormesis or hormetic effect. Full article

This study first analyzes the ecotoxicity of bentazone (BTZ), an herbicide detected in the Albufera Natural Park. BTZ exhibits an EC₅₀ (5 days) towards Lactuca sativa of 900 mg L⁻¹, showing a hormetic effect. The toxic effects of a BTZ, $\mathrm{N}\mathrm{a}\mathrm{C}\mathrm{l}$, and ${\mathrm{N}\mathrm{a}}_2\mathrm{S}{\mathrm{O}}_4$ mixture are generally lower than the individual toxic effects considered additively. However, possible synergy on ecotoxicity was observed at 600 mg L⁻¹ of BTZ in the presence of 2.8 g L⁻¹ of ${\mathrm{N}\mathrm{a}}_2\mathrm{S}{\mathrm{O}}_4$ and 0.8 g L⁻¹ of $\mathrm{N}\mathrm{a}\mathrm{C}\mathrm{l}$. A statistical model was obtained to predict the ecotoxicity thresholds towards Lactuca sativa for combinations of the three compounds. In general, when the concentration of one compound increases, a lower concentration of the others is necessary for the mixture to be toxic. However, in the presence of $\mathrm{N}\mathrm{a}\mathrm{C}\mathrm{l}$, below 382 mg L⁻¹ of BTZ, the concentrations of both compounds need to be increased. This is attributable to the hormetic behavior of BTZ. This BTZ concentration decreases as the ${\mathrm{N}\mathrm{a}}_2\mathrm{S}{\mathrm{O}}_4$ concentration increases. Secondly, the effectiveness of electrooxidation and photoelectrooxidation processes to eliminate BTZ was studied. A ceramic anode made of Sb-${\mathrm{S}\mathrm{n}\mathrm{O}}_2$ and coated with a ${\mathrm{B}\mathrm{i}}_2{\mathrm{W}\mathrm{O}}_6$ photocatalyst was used. The degradation and mineralization degrees achieved using a mixture of 0.46 g L⁻¹ of $\mathrm{N}\mathrm{a}\mathrm{C}\mathrm{l}$ and 1.3 g L⁻¹ of ${\mathrm{N}\mathrm{a}}_2\mathrm{S}{\mathrm{O}}_4$ (like the Albufera lake conditions) show intermediate values between those achieved with pure electrolytes. Specifically, applying 0.6 A, they are very close to the maximum values achieved with pure $\mathrm{N}\mathrm{a}\mathrm{C}\mathrm{l}$. Moreover, the final effluent’s toxicity is significantly lower, especially when light is applied. Therefore, the photoelectrooxidation process applying 0.6 A with the mixed electrolyte is the most effective technique from the combined point of view of final degradation (90.9%), mineralization (62.4%), and toxicity. Full article

Pesticides have been extensively used in agriculture, forestry, and veterinary medicine under intensive production systems. Unfortunately, pesticide pollution resulted in a significant decline in non-target organisms, for instance, in detritivores such as necrophagous insects. Even formulations proposed as less harmful alternatives, such as neonicotinoids like imidacloprid (IMI), have been demonstrated to permeate the trophic chain and trigger severe consequences on non-target species. Here, the intra- and inter-generational effects of a sublethal dose of IMI were explored in the necrophagous greenbottle fly, Lucilia sericata (Meigen, 1826) (Diptera: Calliphoridae). This is because it has been demonstrated that the carcasses of domestic and wild animals can be contaminated with levels of these neonicotinoids. Transgenerational effects, extending up to three generations after a focal application of the pesticide on laboratory-cultivated F₁ flies, were investigated in this study. Morphological, demographic, and phenological features were evaluated through various analyses, including general linear mixed models (GLMM) and Haldane units analyses. Although GLMM showed no significant differences between treatments for the multiple traits observed, a significant directional microevolutionary trend of increased average imago and pupal size was identified for the IMI treatment through Haldane unit analysis. This microevolutionary change falls within the threshold of transgenerational phenotypic plasticity, a crucial mechanism for adaptive responses to environmental stressors. Among the possible explanations for this pattern, it is proposed that this is a likely consequence of the triggering of an epigenetic hormetic transgenerational change. This may contribute to explaining the development of adaptation and resistance towards pesticide formulations in a few generations after focal exposure. In addition to this idea, other possible mechanisms and consequences that explain the observed pattern are discussed. Overall, this experiment highlights the concerns of pesticide spillover consequences, even from sublethal doses of these formulations. Full article

Research Subject: Primary and secondary immunodeficiencies represent a growing clinical and public health challenge due to increased susceptibility to infections, impaired immune regulation, chronic inflammation, and disturbances in redox homeostasis. The pathophysiology of these disorders involves dysfunction of innate and adaptive immunity, altered cytokine production, oxidative stress, and reduced activity of antioxidant defense mechanisms. In recent years, attention has increasingly focused on the role of oxidative imbalance and chronic inflammation in weakening immune function. Ozone therapy, when used at controlled low doses, induces a hormetic response that triggers adaptive antioxidant pathways, modulates cytokine profiles, and enhances the activity of immune cells. Due to these properties, ozone has emerged as a potential adjunctive therapy aimed at restoring immune homeostasis and improving clinical outcomes in patients with immune disorders. Aim of Study: The aim of this review is to discuss the role of oxidative stress and immune dysregulation in the pathogenesis of immunodeficiencies and to provide an updated overview of current evidence regarding the therapeutic potential of ozone therapy. This article summarizes molecular mechanisms, biochemical effects, and clinical findings related to ozone-based interventions, with particular emphasis on cytokine modulation, redox balance, macrophage function, regulatory T cells (Treg), and NK cell activity. Materials and Methods: This review is based on scientific data retrieved from PubMed, Scopus, and Google Scholar. Included sources comprise randomized clinical trials, observational studies, meta-analyses, mechanistic studies, and review articles published between 1996 and 2025. Keywords used during the literature search included: “ozone therapy”, “immunomodulation”, “oxidative stress”, “inborn errors of immunity”, “secondary immunodeficiency”, “Treg cells”, “redox homeostasis”. Results: Analysis of current studies shows that controlled low-dose ozone (typically 10–40 µg/mL) activates the Nrf2/ARE antioxidant pathway, increases enzymatic defense (SOD, catalase, GPx), and reduces levels of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6. Clinical trials report improved lymphocyte profiles, enhanced macrophage phagocytic function, increased Treg activity, and reinforced NK cell responses. Patients receiving ozone therapy demonstrate reductions in inflammatory markers (CRP, IL-6, D-dimer), improved redox balance, decreased infection frequency, and better overall immune performance. The therapy is generally well tolerated when administered within established safety guidelines. Conclusions: Available evidence indicates that ozone therapy may serve as a valuable adjunct in the management of immunodeficiencies by modulating immune responses, reducing oxidative stress, and restoring homeostatic balance. Although current clinical outcomes are promising, further multicenter randomized trials are needed to standardize dosing protocols, assess long-term effectiveness, and confirm safety. Full article

Various non-pharmacological practices have been reported to enhance overall health. The molecular effects of exercise have been shown to involve the upregulation of enzymes and transcription factors that enhance antioxidative and anti-inflammatory activity, boost mitochondrial function and growth, and promote a parasympathetic tone. These beneficial changes occur as an adaptive/hormetic response to an initial increase in oxygen radical and nitric oxide production in working muscles. The redox-sensitive nuclear factor erythroid 2-related factor 2 (Nrf2) was identified as the key mediator of the cellular defense response. A similar adaptive response appears to occur in response to exposure to heat or cold, hyperbaric or hypobaric oxygen, cupping therapy, acupuncture, caloric restriction, and the consumption of polyphenol-rich plant-based foods or spices, and there is direct or indirect evidence for the involvement of Nrf2. In many cases, additional stress signaling pathways have been observed to be upregulated, including the nicotinamide adenine dinucleotide (NAD+)-sirtuin and the adenosine monophosphate (AMP)-activated protein kinase pathways. We conclude that while several traditional health practices may share a hormetic mechanism—mild radical-induced damage triggers a defense response through upregulation of antioxidative, anti-inflammatory, and repair activities, which may impact body-wide tissue function. Full article

This study investigates the phenomenon of ethanol hormesis in honeybees (Apis mellifera) infected with Vairimorpha (Nosema) spp., a widespread parasite that significantly impacts bee health and colony survival. Hormesis refers to a biphasic response where low doses of potentially harmful substances may elicit beneficial effects, contrasting with the detrimental impacts observed at higher concentrations. We hypothesized that low ethanol concentrations could reduce Vairimorpha spp. infection severity and improve bee lifespan. In a controlled experiment, foraging bees were divided into groups of infected and uninfected individuals, and each group (N = 50) was exposed to varying ethanol concentrations (0%, 0.0313%, 0.625%, 1.25%, 2.5%, 5%, and 10%). The results indicated that infected bees exposed to 0.625% and 1.25% ethanol exhibited the longest lifespans and the lowest Vairimorpha (Nosema) spp. spore counts, supporting the hormetic model. In contrast, higher ethanol concentrations (2.5% and above) significantly increased mortality and spore load, reaffirming the toxic effects associated with excessive ethanol intake. This study highlights the complex interactions between ethanol exposure and parasitic infection in honeybees, suggesting that ethanol at 0.625% and 1.25% may mitigate some of the harmful effects of Vairimorpha (Nosema) spp. infections. The findings have implications for understanding how ethanol, present in floral nectar, impacts honeybee health and could inform management strategies for controlling Vairimorpha (Nosema) spp. infections in bee populations. Full article

Background: Chronic pelvic toxicity induced by radiotherapy and/or chemotherapy (R/CIPT) is a debilitating sequela in gynecological cancer survivors, often refractory to conventional treatments and potentially linked to gut microbiota dysbiosis. Ozone therapy (OT), particularly rectal insufflation, demonstrates anti-inflammatory and redox-modulating effects through hormetic mechanisms (Nrf2 activation/NF-κB inhibition). We hypothesize that its clinical benefit is mediated, in part, by restoring gut microbial homeostasis. Objective: This manuscript proposes a clinical study to evaluate the impact of rectal OT on the gut microbiota of patients with gynecological cancers and chronic R/CIPT. Proposed Methods: A prospective, observational study of 38 patients is outlined: 19 with CTCAE v5.0 Grade ≥2 chronic R/CIPT receiving compassionate rectal OT (~40 sessions over 4 months), and 19 matched controls without toxicity. Stool samples for 16S rRNA sequencing will be collected from the OT group pre- and post-intervention and once from controls. Primary endpoints are changes in microbiota composition/diversity and pelvic toxicity scores (CTCAE v5.0, EORTC QLQ-CX24). Secondary endpoints include quality of life (EORTC QLQ-C30, EQ-5D-5L), anxiety/depression (HADS), and serum inflammatory/oxidative stress biomarker analysis. Anticipated Results and Conclusion: This will be the first study to prospectively investigate whether rectal OT’s effect correlates with a beneficial shift in the gut microbiota, specifically an increase in commensals (e.g., short-chain fatty acids producers) and a decrease in pathobionts. If successful, OT could be assessed as a novel, microbiota-targeting intervention for R/CIPT. The findings from this pilot study will provide the necessary groundwork for a future randomized controlled trial to definitively establish causality and efficacy. Full article