Selenium (Se) is a naturally occurring element in both seleniferous and non-seleniferous soils. Plants absorb Se in a variety of ways, mainly as selenate (SeO42-), selenite (SeO32-), and organic compounds such as selenomethionine (SeMet). Selenium significantly impacts plant growth, development, and stress responses. It is a trace element that regulates many physiological and biochemical functions in plants, acts as an antioxidant, and increases plant resistance to abiotic stresses such as heavy metal toxicity, salinity, drought, and severe temperatures. Its beneficial effects depend on the dose and vary depending on the plant species and the environmental conditions. Several functions of Se have been thoroughly discussed in this review, with special attention given to the mechanisms of Se uptake, transport, accumulation, and metabolism. Plants use Se through its assimilation into amino acids (mostly selenocysteine and selenomethionine) and integration into proteins. These processes might have different effects depending on the Se concentration. Furthermore, Se has the potential to be a useful tool in sustainable agriculture, especially in regions where environmental stress is common. This is demonstrated by its ability to increase plant tolerance to various environmental stressors. Recent research shows that Se supplementation not only boosts plant resistance but also enhances secondary metabolite accumulation. Overall, this review concludes that Se plays a dual role in plant systems, acting as both a nutrient and a stress mitigator, and provides opportunities to optimize its use in sustainable agriculture by tailoring Se supplementation to maximize plant tolerance and productivity.

d-limonene is a type of colorless liquid hydrocarbon that falls under the category of cyclic monoterpene. It is the component found in the oil extracted from fruit peels. Isoproterenol, a synthetic β-adrenergic agonist, was administered to rats to induce myocardial injury by increasing heart rate and myocardial oxygen demand, leading to ischemia and oxidative stress. This study aims to investigate the properties of d limonene, against myocardial infarction induced by isoprenaline (ISO) in rats. Male Sprague Dawley rats were treated with d-limonene (200 & 400 mg/kg, p.o) daily for 28 days and administered ISO (85 mg/kg, s.c) on the 29th and 30th days at an interval of 24 hr to induce myocardial injury. Morphological and antioxidant parameters, biochemical markers, lipid profile, troponin-I, cardiac ATPase, heart mitochondrial, and lysosomal enzymes were assayed followed by histopathological screening. Rats treated with isoproterenol (85 mg/kg, s.c), administered twice at an interval of 24 h on 29th and 30th day showed a significant change in morphological and antioxidant parameters, biochemical markers, lipid profile, troponin-I, cardiac ATPase, heart mitochondrial, lysosomal enzymes activities and transcription factor (TNF-α/IL-6/NF-kB) expression. Pretreatment with d-limonene (200 and 400 mg/kg, p.o) for 28 days followed by ISO administration on 29th and 30th day significantly reversed the effects of isoproterenol-induced ischemic changes. Moreover, the biochemical results were validated by histopathological findings. The research indicates that d-limonene demonstrates cardioprotective potential against isoproterenol-induced myocardial infarction. This is attributed to its antioxidant properties, stabilization of myocardial membranes, improved scavenging of free radicals, and inhibition of membrane lipid peroxidation.

Rutin, a dietary flavonoid, exhibits anti-inflammatory, antioxidant, and immunomodulatory properties. The underlying mechanism of protection of rutin against Aflatoxin B1 (AFB1)-induced immunotoxicity is not completely elucidated. This study investigated the protective effect of rutin against Aflatoxin B1 (AFB1)-induced immunotoxicity in male Wistar rats, supported by molecular docking and dynamics simulations.

Forty male Wistar rats were grouped into five: control (corn oil), AFB1 (0.75 mg/kg bwt), AFB1 (1.5 mg/kg bwt), rutin (50 mg/kg bwt), and AFB1 (1.5 mg/kg bwt) + Rutin (50 mg/kg bwt) orally for 30 days.

AFB1 exposure increased (p < 0.05) oxidative and inflammatory markers, altered hematological indices, and caused histological damage in the spleen and bone marrow. Elevated indoleamine 2,3-dioxygenase (IDO) activity, reduced CD4+ T cells, and unchanged tryptophan 2,3-dioxygenase (TDO) activity were also observed. Docking revealed strong binding affinities for AFB1 (-9.5 kcal/mol), rutin (-9.7 kcal/mol), and AFB1-rutin (-10.4 kcal/mol) with IDO. Rutin co-treatment restored oxidative, inflammatory, and hematological indices, mitigated histological damage, and normalized CD4+ T cells and IDO activity, as supported by computational studies.

The activities/expression of immunosuppressive indoleamine 2, 3-dioxygenase is mostly regulated by inflammation and oxidative stress. This study provides new insights into the mechanisms underlying the modulation of immunotoxicity of AFB1 by dietary rutin.

Selenotrisulfides (STS, R-S-Se-S-R) are metabolic intermediates in the bioconversion of inorganic Se species to organoselenium compounds. These Se species are reactive with a variety of endogenous molecules, particularly thiol-containing proteins, with this reactivity facilitating Se transport and subsequent utilization within the body. In this study, X-ray fluorescence microscopy (XFM) and high energy resolution fluorescence detected X-ray absorption spectroscopy (HERFD-XAS) were applied to investigate Se distribution and speciation in vivo. Male rats administered with 1 mg Se/kg b.w. as selenious acid (SA), L-penicillamine selenotrisulfide (PenSSeSPen) or selenenyl penicillamine bound to rat serum albumin (RSA-SSeSPen) showed statistically significant elevations in Se concentrations in the kidney, liver, and blood after 48 h treatment; however, no change in Se concentration was observed in the testes. Notably, XFM revealed a strong colocalization of Se and Cu in the renal cortex, a phenomenon previously observed in cultured cells and in rats fed diets supplemented with 5 mg Se/kg as selenite. Linear combination and principal component analyses of Se Kα1 HERFD-XAS spectra revealed marked differences in Se speciation between the renal cortex and medulla and between red blood cells and plasma for all groups, including the control. STS were identified in linear combination fits of spectra from all tissues, except the testes. These results highlight the vital roles of STS in the intracellular reduction and transport of Se throughout the bloodstream and various tissues.

Sepsis is a serious condition resulting from a dysregulated immune-mediated response to an infection. Myeloid-derived suppressor cells (MDSCs) aggregate and serve a protective function in the pathophysiology of lipopolysaccharide (LPS) shock. However, the regulation of MDSCs by chrysin-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (CHR-NP) remains unexplored. CHR-NP was synthesized and characterized by Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), zeta potential, and dynamic light scattering (DLS). Before being given an intraperitoneal injection of 10 mg/kg of LPS, C57BL/6 mice were given CHR (50 mg/kg), PLGA (50 mg/kg), CHR-NP (50 mg/kg), and dexamethasone (Dexa) (5 mg/kg) by oral administration for 6 days. CHR-NP effectively mitigated LPS-induced splenic injury by diminishing inflammation and oxidative stress. The CHR-NP treatment lowered the amount of malondialdehyde (MDA) and raised the levels of antioxidants like glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx). Besides that, it stopped the production of cytokines that cause inflammation (tumor necrosis factor (TNF)-α, IL-1β, interferon (IFN)-γ, and IL-12) and increased the production of cytokines that stop inflammation (IL-10 and IL-4). This study demonstrates that CHR-NPs confer significant protective effects against LPS-induced sepsis by modulating immune responses, reducing oxidative stress, and alleviating splenic injury. The ability of CHR-NP to enhance antioxidant defenses, suppress pro-inflammatory cytokines, and promote anti-inflammatory mediators highlights its potential as a novel therapeutic approach for regulating MDSCs and mitigating sepsis-related immunopathology.

To understand the role of palmitic acid overload on renal physiology, we exposed female rats to palmitic acid (PA) beyond the physiological range reminiscent of a high-fat western diet. We then treated the rats with graded doses of lycopene (Lyc) to evaluate its potential remedial effect against PA-induced renal injury. Twenty-four rats were randomized into four groups as control (received vehicles; Free Fatty Acid Free Bovine Serum Albumin (BSA) and Olive oil; PA only [received 5 mM BSA-complexed PA]; while the other two groups received 10 and 20 mg/kg body weight of Lyc along with the BSA-complexed PA. The Olive oil-reconstituted Lyc was commenced at the seventh week of intraperitoneal PA injection (uninterrupted) until the nineth week. Our results show that palmitic acid PA overload caused renal lipid dystrophy, characterized by decreased cholesterol, triglycerides, and phospholipids. We also observed elevated activities of lactate dehydrogenase and decreased activity of alanine aminotransferase. The activities of superoxide dismutase, myeloperoxidase, and malondialdehyde levels increased, while glutathione peroxidase activity decreased significantly. Furthermore, PA-induced disruption of cellular electrolytes is characterized by decreased calcium, chloride, sodium, and magnesium ions, and elevated activities of Na+/K+, and Ca2+/Mg2+ ATPases. Western blot analysis shows decreased Nrf2 expression, while NF-KB and Toll -Like Receptor 4 (TLR4) increased. Furthermore, the mRNA expression of TLR4, IL-6, TNF-alpha, and IL-1β increased, while IL-10 decreased in PA only group. However, Lyc treated groups exhibits meaningful ameliorative potentials by abating oxidative stress, inflammation, lipid dystrophy, and iono-dysregulation. This study suggests lycopene supplementation might abate PA -invoked disruption of lipid metabolism, inflammatory signal propagation and disruption of innate antioxidant systems in female albino rats.

The total concentrations of 31 metals and metalloids were determined in the liver of 101 harbour porpoises stranded along the Scottish coastline using CV-AFS, ICP-MS and MP-AES techniques. The proportion of male to female animals was 44:57, with an age range of 0.1 to 15-yr. Principal component analysis showed significant differences by sex (p < 0.01) in the concentrations of 42 % of the elements and were higher in male animals. Higher liver content of elements were observed in the adult age group than in the juveniles. Age-related bioaccumulation of Hg (p < 0.0001) was observed similar to what had also been found in the liver of pilot whales stranded on the coast of Scotland. A strong and positive correlation (p < 0.0001) was shown between Hg and Se, RS = 0.93. A similar correlation (p < 0.0001) was observed between Al and Ga in males, RS = 0.85 and females, RS = 0.91. There was limited information on the interrelationships found between B, Li and Sr. Adult mammals had significantly higher Hg:Se molar ratios than the juveniles (p < 0.0001). However, Se was found in molar excess to Hg in all individuals.

The present study aimed to investigate the diversity of bacterial communities in seleniferous soils using Illumina Mi-Seq Next-Generation Sequencing. This study also compared seleniferous soils (SE) with non-seleniferous (NS) soils to evaluate Selenium (Se) impact on microbial communities and soil properties. Metagenomic analysis identified Proteobacteria as the predominant phylum in both environments, with SE soils exhibiting a higher dominance (48%) than NS soils (31%). The most dominant operational taxonomic unit (OTU) across both soil types belonged to the genus Bacillus. Se altered microbial community composition, increasing the abundance of the Bacillaceae family (30%) and Pseudomonadaceae family (25%) compared to NS soil. Bacillus was the dominant genus in the SE environment indicating its tolerance to selenium. Diversity indices indicated that control soils had higher species richness, while SE soils exhibited a more stressed microbial structure. A consortium of bacterial isolates (Proteus terrae Se3, Halopseudomonas formosensis Se5, and Corynebacterium glutamicum Se38) was inoculated in maize plants cultivated in natural seleniferous soils. Plants inoculated with bacterial consortium grew more healthy and had greater biomass in their roots, shoots, and seeds. Bacterial inoculation results in lesser selenium accumulation in the roots, shoots and seeds of maize plants compared to non-inoculated plants. These results suggest that bacterial species from seleniferous soils may be employed as biofertilizers to enhance plant growth and help plants tolerate Se toxicity in seleniferous soils.

Medicinal plants are rich in nutrients and bioactive compounds, making them potentially suitable for use as chemotherapeutic agents and as additives in aquafeed. Our research evaluated the effects of purslane (Portulaca oleracea) extract supplemented in sunflower-based diets on the growth, carcass composition, blood indices, mineral content, liver antioxidant enzyme profile, and immune response in Cirrhinus mrigala (8.26 ± 0.07 g/fish). The juveniles were fed one of seven different diets-T0 (no extract), T1 (0.5%), T2 (1%), T3 (1.5%), T4 (2%), T5 (2.5%), and T6 (3%)-twice daily, at a feeding rate of 5% of their live body weight. They were stocked in V-shaped steel tanks for 90 days, with 15 juveniles per tank and three replicates per dietary treatment. The results of this research revealed that 1-2% purslane extract substantially enhanced growth indices in fish (p < 0.05). Furthermore, the supplementation of 1-2% dietary purslane extract in the diet significantly lowered fat content and improved protein content (p < 0.05) compared to the diets with 0% and 3% purslane extract inclusion. The outcomes also indicated that the hematology and mineral content in the bodies of juveniles were significantly improved (p < 0.05) at all levels of purslane supplementation, relative to the control groups with 0% and 3% inclusion levels. Moreover, the administration of purslane extract markedly increased the liver antioxidant profile, including glutathione peroxidase, superoxide dismutase, and catalase. Additionally, there was a notable reduction in malondialdehyde levels when fish were fed diets having 1% and 1.5% extract. The findings of this study also revealed improvements in immunological markers, characterized by increased lysozyme activity and elevated total globulin levels. The current research suggests that supplementing C. mrigala diets with 1% purslane extract optimally enhances growth and immunity.

This study investigates the synthesis, characterization and anticancer efficacy of nerolidol-loaded beta cyclodextrin polymeric nanoparticles (NER-βCD-NPs) against MCF-7 breast cancer cells. Nerolidol, a sesquiterpene with anti-inflammatory, antioxidant, antimicrobial and anticancer properties, faces challenges of poor solubility and bioavailability, limiting its therapeutic potential. Breast cancer, a leading cause of cancer-related deaths in women, necessitates alternative therapies with fewer side effects compared to conventional chemotherapy. NER-βCD-NPs were synthesized and characterized using UV-visible spectroscopy, fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta potential analysis and differential scanning calorimetry (DSC). Drug encapsulation efficiency and in vitro release were analyzed using HPLC, while molecular docking assessed NER-βCD interactions. Characterization confirmed successful nanoparticle synthesis. UV-visible spectra and FTIR indicated encapsulation-specific changes, SEM revealed surface morphology, and DLS, zeta potential and DSC analyses demonstrated increased size and stability. The encapsulation efficiency was 84.9%, with 86% NER release at pH 5.4 over 48 h. Docking studies supported strong binding between NER and βCD (binding energy: -3.55 kcal/mol). Cytotoxicity assays showed significant MCF-7 cell inhibition. Mechanistic studies revealed reactive oxygen species (ROS) generation, mitochondrial dysfunction, nuclear changes and cell cycle arrest in the G0-G1 phase. Molecular analysis demonstrated apoptosis through upregulation of Bax, Caspase 6, Caspase 9 and Cytochrome c, alongside Bcl-2 downregulation. These results highlight NER-βCD-NPs as a promising strategy for breast cancer therapy, offering targeted delivery and enhanced therapeutic efficacy while mitigating nerolidol limitations. Further studies are warranted to validate their potential in clinical applications.

The western mosquitofish (Gambusia affinis (G. affinis)) is often the only fish that survives in various selenium-contaminated aquatic environments. However, mechanisms of its survival in such environments remain seldom explored. In this study, the acute toxicity of selenomethionine (Se-Met) in a variety of species (four oviparous and four ovoviviparous species) was evaluated, followed by the chronic effects of Se-Met on G. affinis and on zebrafish (Danio rerio (D. rerio)), focusing on Se accumulation in the gonads and offspring, reproductive biology, and offspring development. Our results showed that the LC50-96h of Se-Met was the largest in G. affinis among the eight fish, confirming its elevated resistance to Se. Meanwhile, the transcripts of genes related to selenoproteins and sulfoproteins showed opposite responses between G. affinis and D. rerio to Se-Met exposure, along with the altered levels of total selenoproteins in oviparous but not in ovoviviparous fish. The chronic exposures showed that Se levels in the gonads, effects on gonadal development and embryonic and early larval development, and Se efflux in the embryos and larvae were apparently different between G. affinis and D. rerio. Finally, differentially expressed genes (particularly antioxidant and inflammation) were mostly stimulated in G. affinis but inhibited in D. rerio. This study has demonstrated that the Se efflux capacity of the offspring and genes related to Se metabolism and antioxidant physiology can help partially explain the survival of G. affinis in Se-contaminated ecosystems.

Palmitic acid (PMA) is abundantly present in substantial quantities within palm oil and manifests neurodegenerative propensities. Conversely, the ingestion of Hesperidin (HSD) is correlated with a reduction in inflammatory markers and mediators. This investigation was meticulously devised to scrutinize the protective potential of HSD against the deleterious repercussions of PMA administration on the cerebral cortex. A cohort comprising forty albino Wistar rats was stratified into four groups, each receiving supplements of HSD and PMA. Remarkably, HSD was observed to fortify the histological framework of the cerebral cortex subsequent to PMA exposure, concurrently diminishing the percentage of apoptotic cells. Furthermore, HSD upregulated the levels of antioxidant markers, preserved the levels of neurotransmitter-associated enzymes, and downregulated the expression of inflammation-regulating genes. In conclusion, PMA exerts toxic effects on the cerebral cortex of albino Wistar rats, leading to increased apoptosis and neuroinflammation, thereby reducing brain cholinergic activity. HSD was found to attenuate the cerebral cortex content of MPO, 5-NTD, ROS, MDA, and NF-κB. Additionally, it elevated the cerebral cortex content of antioxidants and anti-inflammatory markers, thereby shielding it from the deleterious effects of PMA.

Gallic acid (GAL), rutin (RUT), and quercetin (QUE) are common antioxidant agents in fruits and vegetables with intriguing pharmacological effects. In the present study, we compared the therapeutic outcomes of GAL + QUE in comparison with GAL + RUT co-treatment in a busulfan (BUS) model of testicular injury in Wistar rats. BUS (4 mg kg-1 body weight (b.w) was injected intraperitoneally daily for 4 days. GAL + RUT or GAL + QUE (20 mg kg-1 b. w) was delivered by oral gavage for 52 days. Examination of the testes of BUS-treated rats both biochemically and under light microscopy revealed an increased level of lipid peroxidation, DNA fragmentation, glutathione-S-transferase, lactate dehydrogenase, gamma-glutamyl transpeptidase, alkaline phosphatase and acid phosphatase with a concomitant decrease in the level of antioxidants: glutathione, ascorbic acid, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities, suggesting testicular injury. Tissue sections confirmed the testicular injury-induced by BUS, including diminished spermatogenesis score index, tubular diameter, gonado-somatic index, testis weight, epithelia thickness and higher percentage of aberrant tubules. GAL + QUE co-administration had better recovery effects than GAL + RUT on the biochemical markers and protected against BUS-induced testicular damage. GAL + QUE treatment regimen has better capacity to maintain the antioxidant capacity of the testes and is more potent at reducing BUS-induced oxidative damage compared to GAL + RUT.

Polysaccharides derived from seaweeds possess notable immunomodulatory and antioxidant properties. This study investigated the therapeutic potential of polysaccharides extracted from four green seaweed species-Ulva reticulata (URP), Ulva lactuca (ULP), Ulva fasciata (UFP), and Caulerpa racemosa (CRP)-in a cyclophosphamide-induced immunosuppressed in vivo model. Polysaccharides were administered at varying doses over 14 days, with 150 mg/Kg body weight (BW) demonstrating the most pronounced effects. ULP treatment significantly restored body weight (199.5 g) compared to the cyclophosphamide group (155.92 g) and notably improved organ weight indices, particularly liver indices (5.28%). Hematological parameters showed marked improvements, including increased red blood cell count (7.55 × 106/μL), hemoglobin levels (10.98 g/dL), and total leukocyte count (13.78 × 103/μL). Immunoglobulin concentrations were significantly elevated, with IgG reaching 1125.16 and IgM 130.3 mg/dL, alongside a substantial enhancement in survival rates (78.3% vs. 22.4% in the cyclophosphamide group). Antioxidant enzyme activities were significantly enhanced, including superoxide dismutase (96.4%), catalase (0.20 U/mg protein), and lactate dehydrogenase (4.11 μg formazan). Among the species tested, ULP exhibited the most potent immunomodulatory and antioxidant effects, mitigating cyclophosphamide-induced immunosuppression and oxidative stress, thereby highlighting its potential as a therapeutic candidate for immune-related disorders.

The online version contains supplementary material available at 10.1007/s13205-025-04307-4.

The liver plays a crucial role in metabolizing and purging various substances from the body. Exposure to toxins like DMBA (7,12-dimethylbenz[a]anthracene) can harm the liver, leading to inflammation, impaired function, and the potential development of liver lesions or tumors. The present study explored the protective effect of CVC-ZnO QDs (carvacrol-zinc oxide quantum dots) on the liver by DMBA-induced mammary carcinoma. Female Sprague Dawley rats were used, and mammary cancer was initiated by injecting DMBA near the mammary gland. Different concentrations of CVC-ZnO QDs were administered orally to determine the most effective dosage. Various liver tissue factors were evaluated, including liver marker enzymes, antioxidant status, lipid peroxidation, detoxification enzyme activities and protein bound carbohydrates. Additionally, the inflammatory response of the liver tissue was investigated using immunohistochemistry and PCR. Results revealed that rats treated with CVC-ZnO QDs showed a significant decrease in liver marker enzymes, lipid peroxidation levels, Phase I detoxification enzyme activities and protein bound carbohydrates. CVC-ZnO QDs also increased Phase II detoxification enzyme activity, and antioxidant levels compared to rats treated solely with DMBA. Histopathological analysis confirmed that CVC-ZnO QDs shielded the liver from DMBA-induced damage. Furthermore, CVC-ZnO QDs were found to reduce the expression of IL-6, NF-κB, and COX-2 in DMBA-induced rats. Overall, the study demonstrated that administering CVC-ZnO QDs at a dose of 4 mg/kg b.w had a notable hepatoprotective effect against DMBA-induced mammary cancer in rats.

Regenerative organic agriculture (ROA) combines ecological and organic principles to promote soil health, biodiversity, and long-term sustainability. This narrative review explores the connection between soil quality, food nutritional value, and human health, highlighting how ROA can enhance phytochemical content and reduce harmful residues in plant-based foods. Empirical studies report increases in vitamin C, zinc, and polyphenols in crops such as leafy greens, grapes, and carrots grown under regenerative systems, along with reductions in nitrates and pesticide residues. We summarize recent literature (2000-2025) that links soil-driven improvements in food composition to antioxidant activity and potential health benefits. By addressing current research gaps, this review supports the role of ROA in building resilient food systems and preventing chronic disease.

Due to the lack of clinical data, we aimed to assess the anti-cellular senescence and cognition-enhancing effects and the mechanisms of novel tuna-byproduct-derived supplements. An 8-week, three-arm, randomized, double-blind, placebo-controlled parallel study was performed. A total of 60 female perimenopausal and postmenopausal women (45-60 years old) were randomly assigned to placebo, low (2600 mg/day), and high (6000 mg/day) doses of the supplement. The N100 and P300 brain waves, working memory, serum levels of MDA, SOD, CAT, GPx TNF-α, IL-6, eNOS, AChE, MAO, GABA-T, and SIRT1, and density of Lactobacillus and Bifidobacterium spp. in feces were assessed before consumption and every 4 weeks throughout the study period. The telomere length and total phenolic compound and DHA levels were assessed before and at the end of the study. The low dose increased the N100 amplitude, working memory, telomere length, and SIRT1, whereas high doses improved the amplitudes of N00 and P300, P300 latency, and working memory; suppressed AChE, MAO, and GABA-T; and improved MDA, SOD, GPx, TNF-α, and IL-6 levels in the serum, further exhibiting an increase in DHA. Therefore, the novel supplement could be a potential remedy for managing cellular senescence and cognitive decline in perimenopausal and postmenopausal women; however, studies with larger sample sizes are required.

Diabetic nephropathy, a severe problem of diabetes mellitus, is exacerbated by high-fat diets, prompting a need for interventions. Previous study from our laboratory has shown that β-sitosterol, a potent plant sterol has anti-inflammatory and glucose-lowering efficacy by involving insulin metabolic signalling pathway but its role on anti-oxidant signaling pathways, play a crucial role in mitigating oxidative stress and inflammation associated diabetic nephropathy, highlighting its importance as a potential therapeutic target for managing this debilitating complication of diabetes is unknown. This study was aimed to intricate the molecular mechanisms involved in the potential of β-sitosterol (BSIT) on TGF-β1/Nrf2/SIRT1/p53 signaling in high fat diet (HFD) and sucrose induced diabetic nephropathy (DN) in the rat kidney by employing various comprehensive bioinformatic analysis. We have used various comprehensive methods such as pathway predictions, Drug-Protein Interaction, Functional annotation analysis, and molecular docking techniques. Further, in vivo analysis of BSIT on biochemical profiles, gene and protein expression analysis of anti-oxidant and inflammatory signaling molecules was performed in the kidney of high fat diet (HFD) and sucrose-induced diabetic nephropathy. Computational studies provided insights into β-sitosterol's binding affinities and interaction modes with key proteins, suggesting its potential to regulate TGF-β1/Nrf2/SIRT1/p53 signaling pathways. Results of in vivo findings validated computational predictions, showcasing BSIT's multifaceted effects in mitigating diabetic nephropathy and associated complications including regulation of lipid metabolism, combating oxidative stress, and inflammation. The findings underscore BSIT's therapeutic potential by preserving cellular viability, regulating cell death, enhancing antioxidant defence, and stabilizing metabolic processes. Our study concludes that BSIT's ability to potentially regulate TGF-β1/Nrf2/SIRT1/p53 pathways, emphasizing its promising role in managing diabetic nephropathy and associated complications.

Titanium dioxide nanoparticles (TiO2 NPs) are widely distributed in aquatic environments due to their extensive industrial and commercial applications. Several studies have reported the adverse effects of TiO2 NPs on aquatic organisms; however, limited information is available regarding their impact on the freshwater mussel Lamellidens marginalis. The present study investigates the physiological and biochemical responses of L. marginalis following acute exposure (7 days) to varying concentrations of TiO2 NPs (Control, 5.0, 50, and 100 µg/L). Physiological parameters, including the condition index, filtration rate, and clearance rate, were assessed alongside hemocyte count, metabolic activity (electron transport system activity), and energy reserve content (glycogen, lipid, and protein levels). Additionally, oxidative stress biomarkers, including antioxidant enzyme activity, biotransformation enzyme activity, and lipid peroxidation levels, were evaluated. Results revealed a significant accumulation of TiO2 NPs in the gill tissues, accompanied by a marked decline in filtration rate and total hemocyte count, along with an increase in nitric oxide production. Exposure to higher concentrations of TiO2 NPs resulted in substantial alterations in energy reserve levels and oxidative stress biomarkers, indicative of metabolic disruption. Furthermore, mussels exposed to elevated TiO2 NP concentrations exhibited reduced feeding activity and energy expenditure, leading to impaired physiological performance, including potential consequences for growth and reproduction. Histopathological analysis demonstrated pronounced gill damage in mussels from the higher exposure groups. These findings emphasize the ecological risks associated with TiO2 NP contamination and underscore the need for stringent measures to mitigate their impact on freshwater bivalves.

There is a  growing concern about the impact of environmental contamination by metals on insects owing to their biodiversity and important ecological roles. We investigated the neurobehavioral traits, cellular responses, and levels of metals in tissues of Nauphoeta cinerea nymphs exposed, separately and in ternary mixtures, to arsenic (15 and 7.5 mg/L), copper (15 and 7.5 mg/L), and zinc (100 and 50 µg/L), in drinking water for 35 consecutive days. Results showed that the diminutions in locomotor parameters (maximum speed, motility time, and distance traveled), motor and turning capabilities (path efficiency, turn angle, and body rotation) and the increase in anxiety-like behavior (total time freezing and freezing episodes) were more pronounced in individual metal exposure than triple metal mixtures groups. Barring zinc alone group, acetylcholinesterase activity decreased significantly in all the treatment groups compared to the control. The diminutions in glutathione level and antioxidant enzyme activities were partially attenuated in the fat body, midgut, and head of insects in the triple metal mixtures groups. Further, the levels of nitric oxide, hydrogen peroxide, lipid peroxidation, and reactive oxygen and nitrogen species were higher in individual metal exposed insects than the ternary mixture groups. The concentrations of arsenic, copper, and zinc in the fat body, midgut, and head of insects were significantly higher in individual metal exposure groups than the ternary metal mixtures groups. Collectively, the detrimental effects of elevated ecological concentrations of arsenic, copper, and zinc were more pronounced in insects exposed to individual metal than those in ternary mixtures groups.

The most prevalent malignant tumor in the oral cavity, accounting for more than 90% of all oral malignancies, is oral squamous cell carcinoma (OSCC). Therefore, detection or prevention of malignant transformation remains a viable target for the future. Carnosol is a compound derived from rosemary that contains both antioxidant and anti-carcinogens. This study examined the defensive properties of carnosol in DMBA-induced oral carcinogenesis. We have developed the computational based docking analysis to predict the binding affinity and interaction of carnosol with inflammatory and pro-apoptotic proteins. Carnosol was the most potential bioactive compound shows strong binding affinity to low binding energy to bind above the proteins. Following this, we created a hamster model to study buccal pouch carcinogenesis induced by DMBA and assessed buccal tissues using histopathological, biochemical, and western blotting. Carnosol treatment effectively reduced DMBA-induced pathological changes in buccal tissues: Altered detoxification, increased antioxidant levels, and reduced lipid peroxidation enzymes levels. We then examined the impact of carnosol intervention on the modulation of the levels of inflammatory factors and pro-apoptotic markers in oral carcinogenesis. Binding energy was studied between the carnosol between the inflammatory (NF-κB and COX-2) and apoptotic (Bax, caspase-3, and caspase-9) proteins using molecular docking. Our findings suggest that carnosol enhances antioxidant and detoxification levels, potentially prevents oral carcinogenesis by modifying the inflammatory and pro-apoptotic signaling pathways, and acts as an anti-cancer agent.

Monosodium glutamate (MSG) is the most commonly used food additive and has well-known neurotoxic effects. The current study was carried out to assess the underlying mechanisms of the neurotoxicity of MSG on the hippocampus in male rats and examine the protective effect of plasmalogens (Pls) on nuclear factor-B (NF-κB) and p38 MAPK signaling pathways in the hippocampus using behavioral, biochemical, and immunohistochemical methods. Twenty-four male Wistar albino rats were divided into four groups for control or treatment with MSG (2 g/kg body weight) and/or Pls (100 mg/kg body weight). All doses were received orally for 28 days. Results show that plasmalogens ameliorate the levels of glucose, insulin, lipids, oxidative stress markers, antioxidant enzymes, AKT, and neurochemical markers. It also reduces the level of the inflammatory markers TNF-α, NF-κB, and p38 mitogen-activated protein kinase (MAPK). Histological and immunohistochemical alterations in hippocampal tissues were found to be augmented postexposure to Pls, suggesting that Pls have a potent ameliorative effect. We conclude that Pls exert anti-inflammatory, antioxidant, and antiapoptotic effects and counteract MSG-induced neurotoxicity by altering the NF-κB and p38 MAPK signaling pathways.

Accumulation of heavy metals (Mn and Ni) and prolonged exposure to stress are associated with adverse health outcomes. Various studies have shown the impacts of stress and metal exposures on brain function. However, no study has examined the effects of co-exposure to stress, Mn, and Ni on the brain. This study addresses this gap by evaluating oxidative and glial responses, apoptotic activity, as well as cognitive processes in a rat model. Adult Wistar rats were exposed to vehicle (control), restraint stress, 25 mg/kg of manganese (Mn) or nickel (Ni), or combined restraint stress plus Mn or Ni. Following treatment, rats were subjected to several behavioural paradigms to assess cognitive function. Enzyme activity, as well as ATPase levels, were evaluated. Thereafter, an immunohistochemical procedure was utilised to evaluate neurochemical markers of glial function, myelination, oxidative stress, and apoptosis in the hippocampus, prefrontal cortex (PFC), and striatum. Results showed that stress and metal exposure increased oxidative stress markers and reduced antioxidant levels. Further, combined stress and metal exposure reduced various forms of learning and memory ability in rats. In addition, there were alterations in Iba1 activity and Nrf2 levels, reduced Olig2 and myelin basic protein (MBP) levels, and increased caspase-3 expression. These neurotoxic outcomes were mostly exacerbated by co-exposure to stress and metals. Overall, our findings establish that stress and metal exposures impaired cognitive performance, induced oxidative stress and apoptosis, and led to demyelination effects which were worsened by combined stress and metal exposure.

Fluoride (F-) is a major groundwater contaminant spread across the world. In excess concentrations, F- can be detrimental to living beings. F- exposure is linked to cellular redox dyshomeostasis, leading to oxidative stress-mediated pathologies including heart dysfunction. Due to its potent antioxidant properties, various phytochemicals are found to alleviate the symptoms of F- toxicity. Hence, we explore the protective effect of esculin (Esc), a coumarin glucoside on F--induced oxidative stress and cardiotoxicity in zebrafish larvae. The experimental groups consisted of NaF (50 ppm) and Esc (100 μM) groups treated alone and in combination with a control group for 6 h. The groups were maintained till 78 hpf after which the level of oxidants (ROS, LPO, and PCC) and antioxidants (GST, GSH, GPx, SOD, and CAT) were assessed. The results revealed that Esc pretreatment restored the depleted antioxidant markers and reduced the levels of oxidant in the Esc+NaF group, exhibiting its antioxidant potential. In addition, analyses of the heartbeat rate and hemoglobin integrity using o-Dianisidine staining were conducted in the control and experimental groups. Esc treatment prevents F- induced cardiac changes including tachycardia and altered blood flow. Further, the mRNA expression level of antioxidant genes (nrf2, gstp1, hmox1a, prdx1, and nqo1) and cardiac developmental genes (bmp2b, nkx2.5, myh6, and myl7) confirmed that Esc acts as a potent free radical scavenger and antioxidant defense enhancer, protecting zebrafish larvae from NaF-induced oxidative stress and heart dysfunction.

The study investigates the molecular interactions and biological effects of carvacrol zinc oxide quantum dots (CVC-ZnO QDs) on breast cancer in vitro MCF-7 cell lines and in vivo mammary cancer models. Molecular docking using AutoDock Vina revealed binding energies of CVC with key proteins in the PI3K/AKT/mTOR pathway, including PI3K, AKT, PTEN, and mTOR. The results showed significant interaction with specific amino acids, indicating a strong binding affinity. In vitro studies demonstrated a dose-dependent cytotoxic effect of CVC-ZnO QDs on MCF-7 cells, with an IC50 of 20.02 µg/mL, while enhancing intracellular reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP), indicative of apoptosis induction. Antioxidant activity, lipid peroxidation, and nuclear morphological changes were assessed, revealing decreased antioxidant status and increased lipid peroxidation in treated cells. In vivo, CVC-ZnO QDs modulated the PI3K/AKT/mTOR signaling in DMBA-induced mammary cancer in rats, decreasing p-PI3K, p-AKT, and p-mTOR expression while upregulating PTEN. Immunohistochemistry, qRT-PCR, and Western blot analyses confirmed these molecular alterations. The study concludes that CVC-ZnO QDs exert cytotoxic and pro-apoptotic effects on breast cancer cells by modulating the PI3K/Akt/mTOR pathway and promoting oxidative stress, presenting a potential therapeutic strategy for breast cancer management.

Deltamethrin (DMN) is a type-II pyrethroid that has been documented to instigate numerous organ toxicities. Afzelechin (ALN) is a plant based polyphenolic compound that exhibits marvelous biological properties. The present research was conducted to assess the alleviative potential of ALN against DMN induced hepatic dysregulations. Thirty-six male albino (Sprague Dawley) rats were apportioned into four random groups including the control, DMN (5mgkg-1), DMN (5mgkg-1) + ALN (2mgkg-1), and ALN (2mgkg-1) alone administrated group. ALN protected hepatic tissues against DMN induced oxidative stress, inflammation and apoptosis. ALN supplementation donwregulated the gene expression of receptor for advanced glycation end products (RAGE), high mobility group box1 (HMGB1), tumor necrosis factor- α (TNF-α), Myeloid differentiation primary response 88 (MyD88), nuclear factor- kappa B (NF-κB), interleukin-6 (IL-6), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX-2), and interleukin-1β (IL-1β). Besides, ALN administration reduced the levels of reactive oxygen species (ROS) and malondialdehyde while increasing the activities of glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GSR), heme oxygenase-1 (HO-1), superoxide dismutase (SOD) and glutathione (GSH). The levels of hepatic function markers including GGT, ALT, ALP, and AST were lowered while the concentrations of albumin and total proteins were promoted following the ALN treatment. The levels of Bax, Caspase-9 and Caspase-3 were suppressed while the levels of Bcl-2 were escalated after ALN therapy. Moreover, ALN treatment remarkably mitigated DMN induced histological impairments. These findings highlight the hepatoprotective efficacy of ALN against DMN induced liver toxicity.

The hippocampus executes the integration of memory and spatial learning information. This study evaluated the effect of rice bran extract (RBE) on heavy metal mixture (MM) induced hippocampal toxicity and its underlying mechanism in albino rats. Thirty five rats were exposed to MM alone at Pb 20 mg/kg, Al 35 mg/kg, and Mn 0.564 mg/kg body weight or co-exposed with RBE at 125, 250 and 500 mg/kg body weight, 125 RBE mg/kg b.wt only, and 500 RBE mg/kg b.wt only 5 days a wk for 13 wk (90 days). Subsequently, oxidative stress, inflammation (cyclooxygenase-2) and caspase-3, amyloid precursor proteins (Aβ40 and Aβ42), HMOX-1, occludin and BDNF and transcription factor Nrf-2 in the hippocampus were investigated. MM treatment resulted in significantly higher escape latency time than both the control and MM plus RBE group. MM exposure induced increased oxidative stress, inflammation resulting in enhanced hippocampal apoptosis. MM significantly increased bioaccumulation of Pb, Al, and Pb; increased caspase-3, Nrf-2, Aβ40 and Aβ42 and significantly decreased occludin, BDNF, HMOX-1 when compared with the control. All these effects were reversed by RBE. Collectively, RBE ameliorated MM - induced oxidative stress, neuro-inflammation and hippocampal apoptosis via attenuation of oxidative damages of cellular constituents, neuronal inflammation and subsequent down regulation of amyloid precursor proteins Aβ40, Aβ42 and up regulation of occludin, BDNF, HMOX-1 protein expression via Nrf-2 dependent pathways to abrogate hippocampal toxicity associated with spatial learning and memory deficits.

Aflatoxin B1 (AFB1), a mycotoxin commonly present in feed, has several toxic effects. AFB1 seems to have a neurotoxic effect that leads to neurobehavioral impairment. On the other hand, Lutein and Zeaxanthin (LUT/ZEA) have antioxidant and anti-inflammatory effects. Here, we aimed to compare the effects of AFB1 and the co-treatment with LUT/ZEA on neurobehavioural and biochemical changes viz-a-viz oxido-inflammatory response in male rats' hippocampal and pre-frontal cortexes. Experimental rats of the Wistar strain (n = 40) were randomly grouped into treatment cohorts: Control (corn oil 2 mL/kg), AFB1 (75 μg/kg), LUT/ZEA only (100 mg/kg), AFB1 + LUT/ZEA (75 μg/kg + 100 mg/kg), and AFB1 + LUT/ZEA (75 μg/kg + 200 mg/kg). All groups were administered their respective treatment orally for 28 days, while behavioural tests were conducted using open field tests (OFT), Y-maze, novel object tests (NORT), and forced swim tests (FST) 1 h after treatment on day 26-28. The animals were euthanized on day 29. In the hippocampal and pre-frontal cortex, antioxidant indicators (SOD, CAT, GSH, GST, GPx, TSH), inflammatory mediators (XO, NO, MPO), and acetylcholinesterase activity were measured. Our finding presents the anti-oxidant effect of lutein/Zeaxanthin in the brains of AFB1-intoxicated rats, indicating better cognitive and spatial memory capacity in Y-maze and NORT, an improvement in locomotive and explorative behaviour in OFT and reduction in anxio-depressive-like behaviour in LUT/ZEA co-treated rats. Acetylcholinesterase activity was enhanced in LUT/ZEA co-treated rats. LUT/ZEA co-treatment dampened oxido-inflammatory mediators by decreasing XO, NO, and MPO levels and increasing antioxidant activities (SOD, CAT, GSH, GST, GPx, TSH) in the prefrontal and hippocampal cortices. We surmise that mechanistically, co-treatment with LUT/ZEA effectively lessened AFB1 neurotoxicity through anti-inflammatory and antioxidant pathways and essentially improved the experimental rats' neurobehavioural outcomes.

1. Exposure to stress alters normal homoeostasis and, hence, the antioxidant defence system. The aim of this study was to examine the effect of acute cold temperature on the antioxidant defence system in hens.2. Hy-line grey commercial layers (80 40-week-old) were randomly assigned to one of eight groups.  In groups 1 to 5, hens were exposed to low temperature at -8.68°C (cool stressed) for 2, 4, 6, 8 and 10 h, respectively. In groups 6 and 7, post 10 h cool stressed, hens were quickly transferred to room at 21°C to recovery for 2 h and 4h, respectively. In treatment groups 6 and 7, post 10 h cool stressed, hens were quickly transferred to room at 21°C for 2 h and 4 h, respectively. Group 8 was the control, where hens were housed under regular condition at 21°C as controls.3. Antioxidant enzymes (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA), in skeletal muscle, the kidney, liver and pancreas were measured. The transcription of avUCP and ANT mRNA was tested by RT-PCR.4. The T-AOC activity was increased in the skeletal muscle of hens cold stressed for 2, 4, 6, 8 and 10 h and the 2 h recovery groups compared with control hens (p < 0.05). The GPx activity was increased in the liver and skeletal muscle after cold stress 4 h and in the pancreas of cold stress 2 h compared with the control group (p < 0.05). Antioxidant SOD activity was increased in the kidney after cold stress 6 h and in the liver after cold stress 10 h compared to the control group (p < 0.05). Measured MDA activity was increased in the pancreas after 2 h cold stress (p < 0.05).5. UCP mRNA expression level was increased in the pectoral muscle for 2 h and 4 h recovery groups compared with the control hens (p < 0.05) and avian uncoupling protein (UPC), adenine nucleotide translocator (ANT) expression level was increased in the leg muscle of hens cold stress for 2, 6, 8 h and recovery 2 and 4 h.6. The observed changes in the antioxidant defence system were tissue specific. Increments in levels of ANT (leg muscle) and UCP (pectoral and leg muscle) mRNA expression may be involved in the regulation of thermogenesis in skeletal muscle.

Chlorogenic acid (CGA) is a polyphenolic compound widely distributed in the diet. It has been shown to have a variety of potential health benefits and is also administered as a food supplement. However, the report on its safety assessment is sparse. This study is therefore designed to assess the effect of acute exposure to CGA. Forty-eight Swiss mice were weight-matched into eight groups (n = 6). Groups I and II received distilled water and 1% ethanol; Groups III-VIII received 30, 60, 120, 240, 480 and 1000 mg/kg doses of CGA, respectively. Twenty-four hours post-treatment, the liver and kidneys were excised and used for antioxidant assays and kidney and liver function tests. Sections were prepared for histology. Results showed that the concentration of hydrogen peroxide was significantly elevated at all the doses of CGA in the kidney and also in the liver. The liver function parameters were affected in the liver of mice treated with CGA. CGA variably affected potassium ion concentration at the different doses in the kidney. Results were complemented by the histology. CGA manifests a deleterious effect, as evidenced by the perturbations in some of the biochemical parameters in the liver at all the doses, and in particular from the 240 mg/kg dose.

Minerals play an essential role in aquatic animals to maintain their normal physiological and metabolic functions. This feeding trial assessed the impact of various zinc sources on L. rohita performance. Dietary treatments included a Control group with zinc sulfate (226.25 mg/kg), and treatment groups with zinc citrate (150.15 mg/kg), zinc acetate (230.56 mg/kg), zinc monomethionine (244.75 mg/kg), and zinc gluconate (395.94 mg/kg). In 15 aquaria, 300 fish (15.84 ± 0.07g) were randomly distributed in triplicate groups. Results revealed significantly (P < 0.05) higher final body weight (FBW), feed conversion ratio (FCR), body weight gain (BWG), and sediment growth rate (SGR) for zinc gluconate fed fish compared to the other sources. Zinc gluconate fed L. rohita also exhibited the lowest feed intake, while initial body weight (IBW) and survival rate (SR %) did not significantly differ. Proximate fish analysis showed non-significant (P > 0.05) differences among treatments. Tissue zinc analysis demonstrated significantly (P < 0.05) higher zinc content in L. rohita receiving zinc gluconate. Antioxidant enzyme activity indicated lower (2.12 ± 0.01) thiobarbituric acid reactive substances (TBARS) in the zinc gluconate treatment, with elevated levels of key biomarker enzymes, glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Stress and immune response indicators revealed significantly lower hematocrit (HCT), cortisol (CRT), and glucose (GLU) levels in zinc gluconate fed fish, while CRT was higher (36.62 ± 0.65 mg/ml). Blood serum parameters, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), remained lower (29.65 ± 0.85 U/ml, 84.76 ± 2.45 U/ml, and 212.87 ± 6.14 U/ml), in fish fed zinc gluconate respectively. In conclusion, different organic zinc sources, particularly zinc gluconate, improved L. rohita growth, tissue zinc concentration, antioxidant enzyme activity, blood serum parameters, and stress and immune response to varying extents.

Bisdemethoxycurcumin (BDMC) is a naturally occurring compound having anti-cancer properties. We investigated the effect of BDMC on DMBA-induced mammary toxicity in female Wistar rats. Forty-eight virgin female rats were divided into six groups at random. Group 1 received corn oil, group 2 received DMBA (50 mg/kg), groups 3 and 4 received DMBA and BDMC (25 mg/kg and 50 mg/kg), group 5 received BDMC (50 mg/kg), and group 6 received DMBA and vincristine. A single dosage of DMBA was administered (i.p.) at six weeks, followed by BDMC (orally) and vincristine (i.p.) three times a week for thirteen weeks. The DMBA significantly increased lactate dehydrogenase activity by 1.3 folds. Similarly, DMBA increased nitric oxide, malondialdehyde, and myeloperoxidase activities by 12, 204, and 6.3%, respectively. DMBA-rats decreases glutathione-S-transferase, superoxide dismutase, and glutathione peroxidase activities. Immunohistochemistry analysis revealed that B-cell lymphoma-2, estrogen receptor, and human epidermal receptor-2 were strongly expressed in DMBA-rats, but progesterone receptor and Bcl-2 associated protein were weakly expressed. In DMBA rats, histology revealed mammary glands with moderate proliferating ducts and fibrosis. Co-treatment with BDMC reduces hormone receptors activities, improved antioxidant and apoptotic status. BDMC protected the mammary gland from DMBA toxicity by targeting cellular pathways involved in oxidative stress and apoptosis.

Parkinson's disease, a neurodegenerative disorder, affects millions globally, with age, genetics, and environmental conditions increasing risk. Global burden could reach 12 million by 2050. To observe the effect of Celastrus paniculatus in rotenone-induced Parkinsonism in zebrafish model.

The fishes were divided into four groups and the experiment was carried out for 21days. Group I- Control; Group II- Rotenone induced (5 µg/L) dissolved in 0.1% DMSO; Group III - Aqueous extract of Celastrus paniculatus (CP) (20 µg/L) and Group IV - Rot + CP. After 21 days zebrafish was sacrificed and the brain was isolated for further analysis. The neurobehavioral studies were done using open field test, novel tank test and light and dark test, and the cognitive behavior using T-maze and customized fish maze. The antioxidant, neurotransmitter, mitochondrial assay and mRNA expressions were seen.

The rotenone has shown an increased freezing bout, decreased exploration of the tank and average speed has demonstrated motor impairment and also memory impairment was exhibited. There was elevated cortisol and LPO and reduced antioxidant status. The neurotransmitters changes and mitochondrial dysfunction were also observed. The study showed increased in α-synuclein and decreased in DJ1 and LRRK2 expressions. In the present study, the aqueous extract of CP has cognitive dysfunctions and improves memory. CP has also shown amelioration against the production of ROS, mitochondrial dysfunctions and DNA damages caused by rotenone.

CP is known for its medicinal and pharmacological properties. CP has also shown to improve the cognitive dysfunction caused by rotenone and have showed an improvement in effect.

Cobalt (Co) toxicity has been reported to produce central nervous system and gastrointestinal abnormalities. This study assessed the therapeutic effect of cholecalciferol (Cho) supplementation against damages caused by sub-acute (14-day) cobalt chloride (CoCl2) exposure in the brain and intestines. Thirty-five male Wistar rats were divided equally into five groups: Group I (control) received no treatment; Group II received oral CoCl2 (100 mg/kg) only; Groups III, IV, and V received 1000, 3000 and 6000 IU/kg of cholecalciferol, respectively by oral gavage, and concurrently with CoCl2. Cobalt-treated rats showed neuronal vacuolation and presence of pyknotic nuclei in the cerebral cortex and hippocampus, depletion of Purkinje cells in the cerebellum, as well as inflammation and congestion in the intestinal mucosa. Cobalt also increased brain and intestinal hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentrations, while simultaneously reducing glutathione (GSH) content, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities. Further, CoCl2 induced increases in brain acetylcholinesterase (AchE) activity and serum zonulin (ZO-1) levels. Conversely, Cho administration suppressed CoCl2-induced damages in the brain and intestines by reducing lipid peroxidation and increasing the activities of antioxidant enzymes. Remarkably, Cho produced stimulation of brain choline acetyltransferase (ChAT) and suppression of AchE activity, along with dose-dependent reduction in serum levels of ZO-1, intestinal fatty acid-binding protein (iFABP) and nitric oxide. In conclusion, the protective role of cholecalciferol against cobalt-induced toxicity occurred via modulation of cholinergic, intestinal permeability and antioxidant pathways. The results may prove significant in the context of the role of gut-brain connections in neuroprotection.

An experiment was conducted to mitigate mercury and ammonia toxicity (Hg + NH₃) in Oreochromis niloticus (GIFT strain) using selenium nanoparticles (Se-NPs). The Se-NPs were synthesized using green methods, employing fish waste as the substrate. Experimental diets were prepared by supplementing Se-NPs at 0, 0.3, and 0.6 mg kg⁻¹. The oxidative stress enzymes, including catalase (CAT) and glutathione peroxidase (GPx), in the liver and kidney tissues were significantly reduced by Se-NPs at 0.3 and 0.6 mg kg⁻¹ under Hg + NH₃ stress compared to the control and stressor in 20 and 40 day periods. Additionally, superoxide dismutase (SOD) activity in the kidney at 20 days and in the liver at 40 days was significantly reduced by supplementation of Se-NPs under similar conditions. The activity of acetylcholine esterase (AChE), was significantly inhibited by Hg + NH₃ toxicity. Whereas, AChE activity was enhanced by Se-NPs supplementation at 0.3 and 0.6 mg kg⁻¹ during 20 and 40 day intervals. The gene expression of HSP70, iNOS, CYP450, Caspase-3a, and TNFα in liver tissue, and MYST in muscle tissue was upregulated by Hg+NH₃ toxicity. However, this upregulation was significantly downregulated by supplementation of Se-NPs at 0.3 and 0.6 mg kg⁻¹ under Hg + NH₃ stress. Moreover, immunoglobulin (Ig) and growth hormone (GH) levels were noticeably upregulated with Se-NPs compared to the control and Hg+NH₃ stress. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and malate dehydrogenase (MDH) in liver and gill tissues, were significantly elevated by Hg+NH₃ toxicity, were reduced by Se-NPs diet. Conversely, digestive enzyme activities, including protease, amylase, and lipase, were significantly enhanced by Se-NPs under stress conditions. Dietary supplementation with Se-NPs at 0.3 and 0.6 mg kg⁻¹ improved growth performance parameters such as final weight gain percentage, feed conversion ratio, protein conversion ratio, specific growth rate, daily growth index, and relative feed intake compared to the control and other groups. DNA damage, assessed in terms of tail DNA percentage, was significantly reduced with Se-NPs supplementation. Additionally, mercury detoxification was significantly enhanced with Se-NPs-supplemented diets. In conclusion, this study demonstrates that dietary Se-NPs effectively alleviate the adverse effects of mercury and ammonia toxicity by modulating antioxidant status, enhancing immunomodulation, and mitigating stress biomarker impacts through changes in gene expression in fish.

In addition to being able to fight cancer, betanin (BTN) has amazing natural antioxidant and peroxy-radical scavenging properties. 7,12-Dimethylbenz[a]anthracene (DMBA) can impair the activities of enzymes accountable for breaking down xenobiotics and can also cause lipid peroxidation. The study's goal was to find out if betanin could protect against these problems. We determined 100% tumor incidence, abnormal tumor volume, inclined tumor burden, and deduced body weight in DMBA-induced hamsters. We observed diminished lipid peroxidation and enzymatic and nonenzymatic antioxidant activities in DMBA-induced hamsters. The histological study showed that the hamster that receives only DMBA undergoes hyperkeratosis, epithelial hyperplasia, dysplasia, and well-differentiated oral squamous cell carcinoma (OSCC). The hamsters received three different dosages of BTN (10, 20, and 40 mg/kg b.w.) via intragastric intubation for 14 weeks, on alternate days of DMBA painting. The levels of antioxidants, xenobiotic enzymes, and lipid peroxidation (LPO) were significantly restored and inhibited tumor development in a dose-dependent manner. The molecular docking study found high levels of binding affinity in Bax (PDB ID: 2K7W), Caspase-3 (PDB ID: 4JJ8), Caspase-9 (PDB ID: 2AR9), PI3K (PDB ID: 5XGI), AKT (PDB ID: 6BUU), p53 (PDB ID: 1YCS), SMAD-2 (PDB ID: 1DEV), SMAD-4 (PDB ID: 1YGS), SMAD-7 (PDB ID: 2DJY), TGFβ-I (PDB ID: 1PY5), and TGFβ-II (PDB ID: 1M9Z). So, therefore, in vivo and in silico studies were providing prominent anticancer activity of betanin against DMBA-induced oral cancer.

Toxicity is associated with undue sodium fluoride (NaF) exposure, and Betaine (BET) is recognised for its nutraceutical benefits. Although it is necessary to reduce toxic level exposure to fluoride, the literature lacks information on the role of BET in mitigating fluoride-induced reproductive toxicity. Therefore, this study assesses the impact of BET on NaF-induced reproductive perturbation in male rats. Wistar rats were treated with NaF (9 mg/kg) alone or co-treated with BET (50 or 100 mg/kg) for 28 d. Our findings indicate that BET significantly mitigated alterations in sperm functionality indices caused by NaF treatment. BET substantially increased reproductive hormone levels and averted NaF-induced increases in oxidative stress biomarkers and testicular enzymes. NaF-induced increases in inflammatory markers in the testis, epididymis, and hypothalamus were effectively reversed upon BET co-treatment. Also, co-treatment with BET protected genome integrity, as evidenced by p53 and apoptotic markers Bax and Bcl-2 levels, abating damages in the testes, epididymis, and hypothalamus of NaF-treated rats. Also, our findings from in-silico studies revealed that BET moderately inhibits the molecular activation of the inhibitor of nuclear factor-κB kinase, hypoxia-inducible factor -1 alpha, and proviral integration for the Moloney murine leukaemia virus-1 kinase. While it is preferable to reduce fluoride exposure, the relevant findings here indicate that BET exhibits anti-inflammatory, antioxidant, and anti-apoptotic properties that ameliorate inadvertent NaF-mediated toxicities in experimental rats exposed to NaF.

Tangeretin, a flavone compound (O-polymethoxylated) naturally present in tangerine and other citrus peels has demonstrated effectiveness as an anti-inflammatory and neuroprotective agent in several disease model. This study evaluated the impact of tangeretin in mitigating cognitive dysfunction and oxidative stress induced by colchicine in rats, comparing its efficacy with donepezil hydrochloride.

Cognitive dysfunction was induced by administering colchicine (15 µg/rat) intracerebroventricularly (ICV) via a stereotaxic apparatus in male Wistar rats. Colchicine resulted in poor memory retention in acquiring and retaining a spatial navigation task, passive avoidance apparatus, and Morris water maze paradigms. Chronic treatment with tangeretin (at doses of 50, 100, and 200 mg/kg, p.o. once daily) and donepezil hydrochloride (at a dose of 10 mg/kg, p.o. daily) for 28 days, starting seven days before colchicine injection, significantly ameliorated colchicine-induced cognitive impairment.

The biochemical analysis showed that chronic administration of tangeretin effectively reversed the colchicine-induced increase in the level/activity of lipid peroxidation, hydrogen peroxide (H2O2), myeloperoxidase (MPO), nitrite, reactive oxygen species (ROS), tumour necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), serotonin, dopamine, glutamate, amyloid beta (Aβ) peptide, and caspase-3. Tangeretin also reversed the colchicine-induced reduction in the level/activity of brain-derived neurotrophic factor (BDNF), amma-aminobutyric acid (GABA), acetylcholinesterase (AChE), glutathione S-Transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and total thiol (T-SH) in rat brains. However, donepezil hydrochloride did not prevent oxidative stress.

These findings suggest that chronic administration of tangeretin at 50, 100, and 200 mg/kg, p.o. once daily, was protective in mitigating colchicine-induced cognitive impairment and associated oxidative stress. At the same time, donepezil hydrochloride did not demonstrate similar effects.

Asthma is a severe respiratory disease marked by airway inflammation, remodeling, and oxidative stress. β-Glucan (BG), a polysaccharide constituent of fungal cellular structures, exhibits potent immunomodulatory activities. The investigational focus was on the anti-asthmatic and anti-ferroptotic properties of beta-glucan nanoparticles (BG-NPs) in a murine model of allergic asthma induced by ovalbumin (OVA). BG was extracted from Chaga mushrooms (Inonotus obliquus), and its BG-NPs were characterized utilizing techniques including FT-IR, UV visible spectroscopy, zeta potential analysis, DLS, XRD, and TEM. The Balb/C mice were allocated into five groups: control, untreated asthmatic, dexamethasone (Dexa)-treated (1 mg/kg), BG-treated (100 mg/kg), BG-NPs-treated (45 mg/kg), and BG-treated (100 mg/kg). Treatment with BG-NPs markedly diminished the entry of inflammatory cells into the respiratory passage, serum IgE concentrations, DNA damage, and markers of oxidative stress through the reduction of malonaldehyde (MDA) levels and enhancing the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). Furthermore, BG-NPs reduced iron deposition and promoted the transcriptional activity of the GPx4 gene in pulmonary cells, attenuating ferroptosis. The results demonstrated that BG-NPs reduced asthma by inhibiting oxidative stress, inflammation, DNA damage, and ferroptosis. Our results suggest that BG-NPs could be used as potential treatments for allergic asthma.

Fenitrothion (FEN) is an organophosphate insecticidal agent that is considered as major source of organs toxicity. Saponarin (SAP) is a naturally occurring novel flavone that exhibits a wide range of medicinal properties. The current trial was conducted to evaluate the ameliorative potential of SAP against FEN instigated liver toxicity in rats. Thirty-two male albino rats were apportioned into four groups including control, FEN (10 mg/kg), FEN (10 mg/kg) + SAP (80 mg/kg), and SAP (80 mg/kg) alone treated group. It was revealed that FEN administration upregulated the gene expression of TNF-α, TLR4, IL-1β, MYD88, IL-6, TRAF6, COX-2, NF-κB, JAK1 and STAT3 while reducing the gene expression of IκB. Moreover, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were increased while the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (HO-1) and glutathione reductase (GSR) were decreased after FEN exposure. Furthermore, FEN administration notably escalated the levels of hepatic enzymes including alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) whereas reduced the levels of total proteins and albumin. Besides, FEN intake upregulated the levels of Caspase-9, Bax and Caspase-3 while reducing the levels of Bcl-2. Hepatic histology was impaired after FEN intoxication. Nonetheless, SAP treatment remarkably protected the normal state of liver via regulating abovementioned irregularities. Our in-silico analysis confirmed that SAP hold that potential to interact with binding pocket of these proteins, highlighting its ability as a therapeutic compound to alleviate FEN-induced liver damage.

An effective alternative approach to combat aquaculture challenges is the strategic application of bioresources, which not only mitigate disease ailment but also optimize fish growth. Hence, current research was undertaken to highlight the synergic role of bioresources such as plant immunostimulant Ocimum sanctum along with potent gut-derived probiotic Bacillus cereus strain SL1 (Gen Bank Accession Number: FJ627945.1) on mrigal (Cirrhinus mrigala) growth, antioxidant status, gut histopathology, and immune response. For 90 days, fingerlings (average weight 6.8 ± 0.5 g) were fed on diets having varying concentrations of O. sanctum and B. cereus. After the completion of the feeding trial, various growth, immunity, and histological and antioxidant metrics were evaluated according to standard procedures. In comparison to the control and other treatment groups, T3 group showed a significant (P < 0.05) increase in growth parameters, antioxidant enzymatic activity, and hematological and immunological parameters. In addition to it, supplementation of both B. cereus and O. sanctum also upregulated the antioxidant-related gene expressions, such as hepatic catalase gene by 1.89-3.00 folds, hepatic SOD-1 by 4.46-7.52 folds, and GPx-1of the liver by 1.56-1.95 folds. For 10 days, fingerlings were challenged with the pathogenic bacterium Aeromonas hydrophila (MTCC-1739), and maximum survival rate (77.77%) was reported in fingerlings of T3 treatment. Further histopathological studies of gut tissues affirm that O. sanctum and B. cereus play a synergic role in the protection of digestive organs from the pathogenic bacterium A. hydrophila. These results suggest that O. sanctum and B. cereus synergically improved the growth performance, immunity, antioxidant status, and gut histology of C. mrigala leading to its sustainable culture.

Sodium benzoate, a common food preservative, has been linked to oxidative stress, inflammation, and potential damage to various organs, including the kidneys. Aged black garlic (ABG) offers significant potential in supporting body health through its powerful antioxidant and anti-inflammatory properties, which can help reduce cellular damage and inflammation and, thus, improve organ functions. The purpose of this investigation is to investigate the ameliorative effect of aged black garlic extract (ABG extract) on the nephrotoxicity and oxidative stress induced by sodium benzoate. A total of thirty-two adult male albino rats were divided randomly into four groups: Group 1: control; Group 2: orally given ABG extract (200 mg/kg bw) daily for 4 weeks; Group 3: administrated orally by sodium benzoate daily for 4 weeks; Group 4: cotreated with both ABG extract and sodium benzoate for 30 days. This included histological examinations, a histochemical demonstration of DNA contents, and an immunohistochemical demonstration of pro-apoptotic protein caspase-3, as well as a biochemical evaluation of renal MDA, CAT, SOD, GPx, and IL-1β levels. Moreover, serum and urinary urea, uric acid, creatinine, sodium, and potassium levels were also determined, as well as serum C-reactive protein. FI (30 days), FER, and BWG% were calculated as well as urinary volume and protein being measured. The findings revealed that ABG extract significantly improved all histopathological and physiological changes (p < 0.05) induced by SB as renal tissue was significantly improved, DNA contents were restored, and capase-3 immunoreactivity was diminished. Additionally, oxidative and inflammatory markers, and renal function parameters, were significantly improved. These results showed that ABG extract possesses significant ameliorative effects against the nephrotoxicity induced by sodium benzoate; this may be mediated by its antioxidant activity.

An enriched environment (EE) constitutes a proficient strategy that instigates social, cognitive, and motor faculties, fostering healing and heightening learning and memory function after ischemia, while fucoidan derived from brown seaweed encompasses a diverse array of bioactivities and is known to possess neuroprotective properties. This study aims to investigate the effectiveness of combining fucoidan and EE in a rat model of vascular dementia to overcome cognitive challenges. The rats were randomly assigned as Sham, Lesion - 4-vessel occlusion (4VO) i.e., transient global cerebral ischemia (tGCI), 4VO + F50mg/kg, 4VO + EE, and 4VO + F50mg/kg + EE. At the end of the study periods, the rats were exposed to the Novel object task, T-maze, and the Morris water maze. The profile of hippocampal pyramidal neurons and their dendrites was assessed through the CFV, and Golgi cox stained brain sections. Neuroinflammatory markers (IL-1β, IL-6, NF-κB, TNF-α) and synaptogenic markers (BDNF, SYP, PSD-95) were evaluated through western blot analysis. The levels of oxidative stress marker (LPO) and antioxidants (SOD, CAT, GSH, GST, GPX) in the hippocampus were quantified through biochemical assay. The findings revealed that the cognitive deficits were significantly reduced in both the 4VO + F50mg/kg and 4VO + F50mg/kg + EE treatment groups and inflammatory markers were reduced with increased antioxidant levels and synaptogenic markers when compared with the lesion group. However, through this study, the combination therapy involving fucoidan and exposure to an EE was proven effective in preserving neural integrity and restoring cognitive function against the damage caused by oxidative stress and inflammation following tGCI.