Edible insects are traditionally consumed in Uganda and are increasingly recognized as nutritionally valuable and environmentally sustainable food resources. In this study, the nutritional composition, chemical profiles, biological activities, and safety of three commonly consumed edible insects—Ruspolia differens (green and brown morphs) and Macrotermes nigeriensis—were comprehensively evaluated. Extraction yields differed markedly among species, with R. differens morphs showing substantially higher methanolic yields (46.74–48.93

Edible insects are increasingly valued as sustainable functional food sources due to their rich nutritional content, including proteins, essential fatty acids, vitamins, and minerals. This study investigated five insect species/forms traditionally consumed in Indonesia-Phyllophaga helleri (Puthul), Valanga nigricornis (Belalang kayu), Gryllus bimaculatus (Jangkrik), and both the adult (Ulat jati) and cocoon (Entung jati) forms of Hyblaea puera. Methanol and aqueous extracts were evaluated for their inhibitory activities against alpha-glucosidase, alpha-amylase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). Antioxidant and antimicrobial properties were assessed alongside volatile, amino acid, and elemental profiles using GC-MS, LC-MS, and ICP-MS. Volatile analyses revealed limonene (53.9-72.2%) as the dominant aroma compound in Entung jati, Ulat jati, Belalang kayu, and Puthul. Fatty acid profiles were rich in oleic acid (40.8-71.3%), especially in Entung jati and Ulat jati. Alanine and tyrosine were the most abundant amino acids, reaching up to 1945.36 and 4744.03 nmol/mL, respectively. Essential elements (K, Ca, Fe, Cu, Zn, Se) were abundant, while toxic elements (As, Cd, Hg, Pb) were below international safety limits. Entung jati methanol extract showed the strongest alpha-glucosidase inhibition (85.09%), exceeding acarbose (77.61%). Jangkrik exhibited the highest alpha-amylase inhibition (29.45%), and Ulat jati aqueous extract had the strongest antioxidant activity. Some methanol extracts also showed moderate antimicrobial effects (MIC = 625-1250 mu g/mL). P. helleri extract showed cytotoxicity at high doses, but genotoxicity was not observed. These findings support the nutritional and therapeutic potential of Indonesian edible insects.

Extremely low-frequency (ELF) magnetic fields generated by power-line sources are ubiquitous, yet their long-term effects on neuronal cells remain unclear. We investigated whether continuous exposure (72 - 96 h) to a 60 Hz ELF magnetic field induces oxidative DNA damage and alters cell death pathways in differentiated SH-SY5Y human neuroblastoma cells. Neuron-like cells generated by retinoic acid and brain-derived neurotrophic factor were exposed to 1-3 mT ELF magnetic fields for 96 h, with sham-exposed cells as controls. Chromosomal integrity (Hoechst 33258 staining), apoptosis/necrosis (Annexin V-FITC/propidium iodide flow cytometry), oxidative DNA damage (apurinic/apyrimidinic site analysis), and redox balance (total oxidant and total antioxidant status) were assessed. ELF magnetic field exposure caused intensity dependent nuclear abnormalities, increased oxidative DNA lesions, early oxidative imbalance, and a predominance of necrotic over apoptotic cell death. These findings indicate that continuous low-intensity ELF magnetic field exposure disrupts redox homeostasis and compromises genomic stability in differentiated neuronal cells.

In this work, we evaluated the chemical composition and the potential of ethyl acetate fractions of propolis from Babor (EAFPB) and El-Menia (EAFPM) regions against human neuroblastoma SH-SY5Y. The inhibitory of MDM2-P53 interaction by propolis phytochemicals was also evaluated by molecular docking and molecular dynamics simulations. HPLC-DAD revealed the predominance of phenolic acids such as vanillic acid, p-coumaric acid, cynarin; and flavonoids such as naringenin, hesperetin and hesperidin. Besides, fumaric acid and esculetin were detected for the first time in Algerian propolis. In vitro studies validated the selective anticancer and apoptotic properties of propolis fractions, and confirmed the absence of genotoxic effects. Molecular docking and molecular dynamics revealed good binding affinities and stable interactions of Kaempferol, Naringenin, Hesperetin, Apigenin and Luteolin with MDM2. Overall, the findings highlight the potential of Algerian propolis-derived compounds as selective anticancer agents against neuroblastoma.

Bilacunaria microcarpa, a traditionally consumed yet underexplored species of the Apiaceae family, was evaluated for its neuroprotective potential in an in vitro Parkinson’s disease model induced by 1-methyl-4-phenylpyridinium (MPP⁺). Differentiated SH-SY5Y neuronal cells were co-treated with MPP⁺ and aqueous extracts derived from the plant’s flowers, stems, and leaves. Cell viability was assessed using the MTT assay, while nuclear morphology was examined via Hoechst 33258 staining. Enzymatic activities of AChE and caspase-3 were analyzed to investigate cholinergic and apoptotic responses, respectively. The antioxidant and oxidant status of the samples was determined by measuring the total antioxidant status and total oxidant levels. Chemical profiling analysis by HPLC-DAD identified chlorogenic acid as the predominant compound across all plant parts. The extracts demonstrated substantial enhancement in cell viability and were non-cytotoxic in fibroblast cultures. Moreover, all sample extracts caused a statistically significant reduction in caspase − 3 activity (p < 0.05). Furthermore, in silico blood-brain barrier permeability predictions indicated that some phytochemicals present in the extracts, such as resveratrol, o-coumaric acid, hydroxybenzoic acid, and vanillin, have the potential to permeate the blood-brain barrier. These outcomes indicate that Bilacunaria microcarpa exhibits considerable potential as a neuroprotective agent, warranting further exploration as a candidate for the development of therapeutic interventions for Parkinson’s disease.

Neurodegenerative disorders are characterized by progressive neuronal dysfunction, cholinergic impairment, and disruption of cellular homeostasis. Ionic balance and metabolic stability are increasingly recognized as critical contributors to neuronal resilience under injurious conditions. The present study aimed to evaluate the potential protective effects of selected sodium (Na⁺) and potassium (K⁺) salts in differentiated SH-SY5Y neuronal cells subjected to hydrogen peroxide (H₂O₂; 100 µM), a widely used model of neuronal injury. Following H₂O₂ exposure, cells were treated with non-toxic concentrations of the following salts: Sodium citrate tribasic dihydrate (Na₃C₆H₅O₇·2H₂O), Sodium hydrogen carbonate (NaHCO₃), Disodium hydrogen phosphate (Na₂HPO₄), Potassium sodium tartrate tetrahydrate (KNaC₄H₄O₆·4H₂O). Salt treatments ameliorated the decline in cell viability and partially reversed changes in total antioxidant status (TAS), total oxidant status (TOS), and acetylcholinesterase (AChE) activity induced by H₂O₂. To further explore potential mechanistic interactions, molecular docking and molecular dynamics (MD) simulations were conducted on human AChE. The salts were found to interact primarily with peripheral residues surrounding the active-site gorge, suggesting a possible allosteric influence rather than direct engagement with the catalytic triad. Among the tested compounds, disodium hydrogen phosphate (Na₂HPO₄) exhibited the most stable binding profile over 100 ns MD simulations. Overall, these findings provide preliminary evidence that selected Na⁺- and K⁺-based salts may attenuate neuronal injury and support cellular function under stress conditions. Given their established safety profiles and accessibility, these compounds warrant further investigation as potential adjunctive agents for mitigating processes relevant to neurodegeneration.

Biofilms are implicated in most chronic infections and exhibit up to 1000-fold higher antibiotic resistance than planktonic cells, creating an urgent need for new antibiofilm agents. Here, we characterized GK-11, an 11-amino acid derivative of pleurocidin. Although GK-11 showed limited antimicrobial activity (MIC: 64 µg/mL for Staphylococcus aureus and 256 µg/mL for Pseudomonas aeruginosa), it demonstrated potent antibiofilm effects at sub-MIC levels (MBIC: 32 µg/mL and 16 µg/mL, respectively). Microscopy and SEM confirmed disruption of biofilm structure, while qRT-PCR revealed downregulation of key virulence genes. GK-11 was non-toxic to Caenorhabditis elegans and maintained > 80

The development of multifunctional implant coatings that promote biocompatibility while inhibiting bacterial adhesion is of critical importance in orthopedic and dental applications. In this study, Tantalum-Boron Nitride (Ta-BN) composite thin films were fabricated via dual-target magnetron sputtering at power levels of 15 W, 20 W, and 25 W, and their structural, biological, and antibacterial properties were evaluated. X-ray diffraction revealed amorphous structures for all coatings, while SEM confirmed dense, void-free morphologies. EDS showed a power-dependent compositional shift, with the 20 W group displaying the most balanced distribution (57.45% Ta, 32.55% B, 10.00% N). Biocompatibility testing with Saos-2 cells demonstrated the highest viability for the 20 W coating (91.3 f 5.2%), closely approximating the control (100 f 4.7%), whereas 15 W and 25 W coatings showed reduced values. Fluorescence microscopy further confirmed superior cell adhesion and uniform coverage on the 20 W surface. Antibacterial assays against E. coli revealed the strongest effect at 20 W, with bacterial viability reduced to 53.4 f 4.2%, outperforming both 15 W (79.5 f 6.3%) and 25 W (66.7 f 5.1%). These results indicate that Ta-BN coatings deposited at 20 W offer the optimal balance of biocompatibility and antibacterial performance, making them strong candidates for next-generation implant surface modifications.

Glioblastoma (GBM) remains one of the most lethal primary brain tumors, characterized by aggressive proliferation, marked therapeutic resistance, and limited responsiveness to standard chemoradiotherapy. Therefore, identifying combination strategies capable of enhancing cytotoxic efficacy while minimizing toxicity is of considerable interest. In this study, we investigated the antitumor potential of Farnesene, a sesquiterpene natural compound, alone and in combination with the anthracycline chemotherapeutic Daunorubicin in U87MG glioblastoma cells. MTT assays demonstrated that Farnesene exerts strong tumor-selective cytotoxicity, with an IC₅₀ value of 4.65 µM in U87MG cells compared with 264.0 µM in non-malignant HDFa fibroblasts. Daunorubicin also reduced viability in a dose-dependent manner (IC₅₀ = 9.81 µM in U87MG), although with lower selectivity. Fixed-ratio combination analyses revealed pronounced synergism, as evidenced by markedly negative Bliss scores, high Highest Single Agent (HSA) advantages, and Combination Index values below 1 at submaximal concentrations. Flow cytometry using Annexin V/PI staining confirmed that the combination significantly increased both early and late apoptotic populations relative to monotherapies. FDA/PI fluorescent imaging supported these findings, showing a substantial elevation in non-viable PI-positive cells, whereas Hoechst 33,258 staining indicated preserved nuclear morphology at 24 h, consistent with early apoptotic engagement rather than immediate genotoxic collapse. Our results suggest that Farnesene not only exhibits potent and selective cytotoxicity toward glioblastoma cells but also enhances Daunorubicin-induced apoptosis through synergistic interactions. These findings highlight the preclinical potential of this combination and provide a rationale for further mechanistic and in vivo evaluation in experimental GBM models.

The strategic design of small-molecule fluorescent probes is critical for advancing precision bioimaging in both cellular and microbiological contexts. In this study, we report a series of anthracene-pyridine derivatives-compounds 3a, 3b, and 3c-with nitrogen atoms positioned at the ortho, meta, and para positions, respectively, to investigate how atomic-level substitution patterns govern photophysical properties and imaging performance. Spectroscopic characterization revealed that the para-substituted compound 3c exhibits enhanced intramolecular charge transfer (ICT) character, leading to lower fluorescence quantum yield in polar biological environments due to increased non-radiative decay. In contrast, the meta-substituted derivative 3b maintains a more locally excited (LE)-like emission, producing intense blue fluorescence and demonstrating high selectivity for bacterial imaging, likely due to favourable interactions with nucleic acids or membranes. Ortho-substituted compound 3a also displayed appreciable fluorescence in mammalian cells, though with lower intensity and reduced bacterial uptake. Complementary molecular dynamics simulations revealed that nitrogen positioning influences molecular geometry, conformational stability, and interaction propensities with biological targets, thereby shaping the observed bioimaging performance. Collectively, these findings establish clear structure-property-function relationships, underscoring how fine-tuning nitrogen placement can optimize excited-state behaviour, cellular uptake, and emission output. These insights provide a valuable framework for the rational design of next-generation fluorophores tailored for multicolour and environment-sensitive imaging applications.

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor and remains highly resistant to standard therapies. Because redox homeostasis is frequently altered in GBM, small natural products that affect viability together with oxidative-stress endpoints may provide promising leads for further development. Here, we evaluated the terpenoids α-pinene, farnesene, carvone, and terpinolene for cytotoxicity and selectivity in human glioblastoma (U87MG) cells compared with primary human dermal fibroblasts (HDFa). Cell viability was assessed by the MTT assay, and nuclear morphology was evaluated using Hoechst 33,258 staining. Apoptosis-related effects were examined by measuring caspase-3 activity, and oxidative balance was assessed using total antioxidant status (TAS) and total oxidant status (TOS) assays. The terpenoids reduced U87MG viability in a concentration-dependent manner while showing substantially lower toxicity in HDFa cells. At 30 µg/mL, all tested terpenoids increased caspase-3 activity in U87MG cells and were associated with increased TAS and decreased TOS relative to control. Overall, these findings identify these terpenoids as selective in vitro hits against U87MG cells and support follow-up studies incorporating direct ROS profiling and expanded apoptosis assays to clarify mechanism.

Alzheimer's disease is linked with diabetes and cancer, emphasising the need for effective treatments. Plantago lanceolata, recognised as safe by various pharmacopeias, was investigated in this study for therapeutic potential. We examined the effects of its leaf extracts and sub-extracts (methanol, hexane, dichloromethane, ethyl acetate, butanol, aqueous) on AChE, BChE, α-amylase, α-glucosidase enzymes, as well as their impact on HDF-a and U87-MG cancer cells. The phytochemical characterisation was performed using ICP-MS and LC-MS/MS. Cytotoxic effects were evaluated on HDF-a and U87-MG cell lines, along with assessments for nuclear abnormalities. Na and K were detected in extracts, with isoleucine and cyanidin-3-O-glucoside being the most concentrated compounds. Extracts at concentrations exceeding 25 µg/mL significantly increased cytotoxicity in HDF-a cell lines compared to the control group, without inducing nuclear abnormalities. Methanol extract demonstrated moderate inhibition against AChE and BChE at concentrations of 100 µg/mL and 500 µg/mL, respectively. These findings suggest that extracts exhibit potential therapeutic effects.

Diabetes mellitus (DM) and cancer are multifactorial diseases with significant health consequences, and their relationship with aging makes them particularly challenging. Epidemiological data suggests that individuals with DM are more susceptible to certain cancers. This study examined the bioactive properties of Hypericum scabrum extracts, including methanol, hexane, and others, focusing on their inhibitory effects on key enzymes associated with DM and neurodegenerative diseases, such as acetylcholinesterase, butyrylcholinesterase, α-amylase, and α-glucosidase. Additionally, the impact of these extracts on human fibroblast (HDFa) and glioblastoma (U87MG) cancer cells was evaluated. The methanol extract was analyzed for elemental composition using ICP-MS, secondary metabolites, and amino acids via LC–MS/MS and underwent morphological and anatomical characterization. The methanol extract demonstrated notable inhibitory activity, with an IC50 value of < 1 µg/mL against α-glucosidase, surpassing acarbose in efficacy. The flower essential oil exhibited the highest inhibition (79.95

Limited advancements in managing malignant brain tumors have resulted in poor prognoses for glioblastoma (GBM) patients. Standard treatment involves surgery, radiotherapy, and chemotherapy, which lack specificity and damage healthy brain tissue. Boron-containing compounds, such as boric acid (BA), exhibit diverse biological effects, including anticancer properties. This study aimed to examine whether boron supplementation, as BA, can inhibit glioblastoma growth in a xenograft animal model. Using MRI-based tumor size measurement, survival rates, hematological, clinical biochemistry analyses, and genotoxicity parameters, we assessed the impact of BA. Histopathological, immunohistochemical, and immunofluorescence examinations were also conducted. All BA doses (3.25, 6.5, and 13 mg kg−1 b.w.) extended survival compared to GBM controls after 14 days, with a dose-dependent anti-GBM effect observed in MRI analyses. BA treatment improved hematological (WBC and PLT counts) and biochemical parameters (LDL-C, CREA, and ALP). Histopathological examination revealed a significant reduction in tumor diameter with 6.5 and 13 mg kg−1 BA. Immunohistochemical and immunofluorescence staining showed modulation of intracytoplasmic Ki67, cytoplasmic CMPK2, and GFAP expressions in tumor cells post-BA treatment. Additionally, BA did not increase micronuclei formations, indicating its non-genotoxic nature. In conclusion, targeting tumor suppressor networks with boron demonstrates significant therapeutic potential for GBM treatment.

Objective: Diabetic retinopathy (DR), considered one of the most common microvascular complications associated with diabetes mellitus (DM), involves both neuronal and vascular dysfunctions in the retina. Neuronal damage and vision loss occur progressively in patients with DR. A number of genetic targets have been identified for DR and gene-related treatments as well as early diagnostic techniques have been developed. Despite some medical advances, DR remains a devastating complication of diabetes. This study aimed to identify new gene targets that can be used for the prognosis and treatment of DR.. Materials and Methods: Eight candidate genes were analyzed using Synergy Brands Green (SYBR-green)- based real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) from 45 individuals: DR patients (n=15), DM patients without DR (n=15), and healthy controls (n=15). STRING v11 was used for protein-protein interaction analysis. Gene expression differences were evaluated using ANOVA, with significance set at P < .05. Results: HIF1A and VEGFA were significantly upregulated in both DR and DM groups compared to controls (HIF1A: fold change 5.28; VEGFA: fold change 5.20 for DR group). SERPING1 was specifically upregulated in DR patients (fold change 3.42). CX3CR1 and BDNF were downregulated in both DR and DM groups (CX3CR1: fold change 8.32; BDNF: fold change 3.21), while IGFBP3 was significantly downregulated only in DR patients (fold change 6.5). STRING analysis revealed strong interactions between SERPING1 and complement pathway components, while IGFBP3 was linked to insulin-like growth factor signaling. Conclusion: In light of these findings, we observed that SERPING1 and IGFBP3 genes might be proposed as targets for early diagnosis and treatment for DR.

Background/Objectives: Over the past 25 years, numerous biological molecules, like recombinant lysosomal enzymes, neurotrophins, receptors, and therapeutic antibodies, have been tested in clinical trials for neurological diseases. However, achieving significant success in clinical applications has remained elusive. A primary challenge has been the inability of these molecules to traverse the blood–brain barrier (BBB). Recognizing this hurdle, our study aimed to utilize niosomes as delivery vehicles, leveraging the “molecular Trojan horse” technology, to enhance the transport of molecules across the BBB. Methods: Previously synthesized memantine derivatives (MP1–4) were encapsulated into niosomes for improved BBB permeability, hypothesizing that this approach could minimize peripheral drug toxicity while ensuring targeted brain delivery. Using the human neuroblastoma (SH-SY5Y) cell line differentiated into neuron-like structures with retinoic acid and then exposed to amyloid beta 1–42 peptide, we established an in vitro Alzheimer’s disease (AD) model. In this model, the potential usability of MP1–4 was assessed through viability tests (MTT) and toxicological response analysis. The niosomes’ particle size and morphological structures were characterized using scanning electron microscopy (SEM), with their loading and release capacities determined via UV spectroscopy. Crucially, the ability of the niosomes to cross the BBB and their potential anti-Alzheimer efficacy were analyzed in an in vitro transwell system with endothelial cells. Results: The niosomal formulations demonstrated effective drug encapsulation (encapsulation efficiency: 85.3% ± 2.7%), controlled release (72 h release: 38.5% ± 1.2%), and stable morphology (PDI: 0.22 ± 0.03, zeta potential: −31.4 ± 1.5 mV). Among the derivatives, MP1, MP2, and MP4 exhibited significant neuroprotective effects, enhancing cell viability by approximately 40% (p < 0.05) in the presence of Aβ1-42 at a concentration of 47 µg/mL. The niosomal delivery system improved BBB permeability by 2.5-fold compared to free drug derivatives, as confirmed using an in vitro bEnd.3 cell model. Conclusions: Memantine-loaded niosomes provide a promising platform for overcoming BBB limitations and enhancing the therapeutic efficacy of Alzheimer’s disease treatments. This study highlights the potential of nanotechnology-based delivery systems in developing targeted therapies for neurodegenerative diseases. Further in vivo studies are warranted to validate these findings and explore clinical applications.

Background: Mitochondrial dysfunction and metabolic abnormalities are acknowledged as significant factors in the onset of neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Our research has demonstrated that the use of combined metabolic activators (CMA) may alleviate metabolic dysfunctions and stimulate mitochondrial metabolism. Therefore, the use of CMA could potentially be an effective therapeutic strategy to slow down or halt the progression of PD and AD. CMAs include substances such as the glutathione precursors (L-serine and N-acetyl cysteine), the NAD+ precursor (nicotinamide riboside), and L-carnitine tartrate. Methods: Here, we tested the effect of two different formulations, including CMA1 (nicotinamide riboside, L-serine, N-acetyl cysteine, L-carnitine tartrate), and CMA2 (nicotinamide, L-serine, N-acetyl cysteine, L-carnitine tartrate), as well as their individual components, on the animal models of AD and PD. We assessed the brain and liver tissues for pathological changes and immunohistochemical markers. Additionally, in the case of PD, we performed behavioral tests and measured responses to apomorphine-induced rotations. Findings: Histological analysis showed that the administration of both CMA1 and CMA2 formulations led to improvements in hyperemia, degeneration, and necrosis in neurons for both AD and PD models. Moreover, the administration of CMA2 showed a superior effect compared to CMA1. This was further corroborated by immunohistochemical data, which indicated a reduction in immunoreactivity in the neurons. Additionally, notable metabolic enhancements in liver tissues were observed using both formulations. In PD rat models, the administration of both formulations positively influenced the behavioral functions of the animals. Interpretation: Our findings suggest that the administration of both CMA1 and CMA2 markedly enhanced metabolic and behavioral outcomes, aligning with neuro-histological observations. These findings underscore the promise of CMA2 administration as an effective therapeutic strategy for enhancing metabolic parameters and cognitive function in AD and PD patients.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) stands as one of the most potent halogenated polycyclic hydrocarbons, known to inflict substantial cytotoxic effects on both animal and human tissues. Its widespread presence and recalcitrance make it an environmental and health concern. Efforts are being intensively channeled to uncover strategies that could mitigate the adverse health outcomes associated with TCDD exposure. In the realm of counteractive agents, boron compounds are emerging as potential candidates. These compounds, which have found applications in a spectrum of industries ranging from agriculture to pharmaceutical and cosmetic manufacturing, are known to modulate several cellular processes and enzymatic pathways. However, the dose–response relationships and protective potentials of commercially prevalent boron compounds, such as boric acid (BA), ulexite (UX), and borax (BX), have not been comprehensively studied. In our detailed investigation, when peripheral blood mononuclear cells (PBMCs) were subjected to TCDD exposure, they manifested significant cellular disruptions. This was evidenced by compromised membrane integrity, a marked reduction in antioxidant defense mechanisms, and a surge in the malondialdehyde (MDA) levels, a recognized marker for oxidative stress. On the genomic front, increased 8-OH-dG levels and chromosomal aberration (CA) frequency suggested that TCDD had the potential to cause DNA damage. Notably, our experiments have revealed that boron compounds could act as protective agents against these disruptions. They exhibited a pronounced ability to diminish the cytotoxic, genotoxic, and oxidative stress outcomes instigated by TCDD. Thus, our findings shed light on the promising role of boron compounds. In specific dosages, they may not only counteract the detrimental effects of TCDD but also serve as potential chemopreventive agents, safeguarding the cellular and genomic integrity of PBMCs.

Nowadays, the unique features of nanoparticles (NPs) have encouraged new applications in different areas including biology, medicine, agriculture, and electronics. Their quick joining into daily life not only enhances the uses of NPs in a wide range of modern technologies but also their release into the aquatic environment causes inevitable environmental concerns. On the other hand boron exhibits key physiological effects on biological systems. This research was designed for evaluating the toxicity of magnetite nanoparticles (Fe3O4-MNPs) on aquatic organisms and obtaining data for the information gap in this area. In this study, Rainbow trout (Oncorhynchus mykiss) was considered as an aquatic indicator, and trials were designed as Ulexite (a boron mineral, UX) treatment against exposure to Fe3O4-MNPs. Synthesized and characterized Fe3O4-MNPs were exposed to rainbow trouts in wide spectrum concentrations (0.005-0.08 mL/L) to analyze its lethal dose (LC50) and cytoprotective properties by UX treatment were assessed against Fe3O4-MNPs applications for 96 h. For the initial toxicity analysis, hematological parameters (blood cell counts) were examined in experimental groups and micronucleus (MN) assay was performed to monitor nuclear abnormalities after exposure to NPs. Biochemical analyzes in both blood and liver samples were utilized to assess antioxidant/oxidative stress and inflammatory parameters. Also, 8-hydroxy-2'-deoxyguanosine (8-OHdG) assay was used to investigate oxidative DNA lesions and Caspase-3 analysis was performed on both blood and liver tissues to monitor apoptotic cell death occurrence. When antioxidant enzymes in blood and liver tissue were examined, time-dependent decreases in activity were determined in SOD, CAT, GPx, and GSH enzymes, while increased levels of MDA and MPO parameters were observed in respect to Fe3O4-MNPs exposure. It was found that TNF-α, Il-6 levels were enhanced against Fe3O4-MNPs treatment, but Nrf-2 levels were decreased at the 46th and 96th h. In the 96th application results, all parameters were statistically significant (p < 0.05) in blood and liver tissue, except for the IL-6 results. It was determined that the frequency of MN, the level of 8-OHdG and caspase-3 activity increased in respect to Fe3O4-MNPs exposure over time. Treatment with UX alleviated Fe3O4-MNPs-induced hematotoxic and hepatotoxic alterations as well as oxidative and genetic damages. Our findings offer strong evidence for the use of UX as promising, safe and natural protective agents against environmental toxicity of magnetite nanoparticles.