Purinergic signaling plays a key role in cellular processes including proliferation, migration, and survival, which are essential for tumor progression. The aim of this study was to investigate effects of polyoxotungstate-1 (POM-1), a purinergic enzyme inhibitor, on viability, migration, and enzymatic activity of B16-F10 melanoma cells. To simulate a tumor microenvironment with impaired extracellular nucleotide degradation and ATP accumulation, effects of POM-1 (50-1000 µM), ATP (1-1000 µM), and their combined treatment were determined after 24 and 72 h. POM-1 effects on purinergic enzymes, oxidative stress, cytokine secretion, and tumor-related cellular functions were measured. POM-1 reduced cell viability, particularly at 250 and 1000 µM after 72 h, with reductions reaching 79% at 1000 µM. ATP exhibited a biphasic effect, with low concentrations enhancing cell viability and function, while high concentrations induced cytotoxicity, diminishing viability by 60% at 1000 µM after 72 h. Combined treatment with POM-1 and ATP enhanced cytotoxicity, reaching approximately 90-92% inhibition cell proliferation. POM-1 elevated ROS and NO levels by 113% and 202%, respectively, and enhanced LDH activity release by up to 144%, indicating cellular damage, and impaired migration, adhesion, and clonogenic capacity, including up to 89% inhibition cell migration and 83% reduction in colony formation. Enzymatic analyses demonstrated that POM-1 inhibited NTPDase activity, altering extracellular nucleotide dynamics, reaching approximately 95% decreased ATP hydrolysis and 80% diminished AMP hydrolysis at higher concentrations. These findings demonstrate that exposure to POM-1 modulates purinergic signaling and induces cytotoxic and functional alterations in murine B16-F10 melanoma cells.
Many U.S. soldiers and support personnel stationed in the Middle East and Southwest Asia are exposed to hazardous combustion byproducts from military burn pits, which may produce chronic health effects. In addition, prolonged and irregular work schedules increase susceptibility to circadian rhythm disruption, worsening adverse health outcomes. This study aimed to examine the interaction between light at night and burn pit exposure and their effects on neuroinflammatory and behavioral outcomes in mice. Thirty-two male Swiss Webster mice were housed either in dark nights (LD) or dim light at night (DLAN) condition. During week 4, mice from each group were exposed to either filtered air (FA) or burn pit emissions (BPE) for 4 hr/ day over 6 days. For the BPE‑exposed mice, the average exposure concentrations were 6.9 mg/m3 (mass) and 4.03E6 #/cc (particle counts). The mice housed in LD conditions and exposed to FA served as an experimental control group. Behavioral testing conducted 24 hr after the last exposure resulted in no significant differences in distance traveled, spatial working memory, or anxiety-like behavior in open field, y-maze, and elevated plus maze. However, DLAN-FA mice exhibited reduced average speed in comparison to LD-FA. qRT-PCR analysis revealed decreased expression of proinflammatory cytokine genes in hippocampus (Il6, Tnfα, and Il1β) and cortex (Il6) of LD-BPE mice. Significant changes in gene expression were not observed in lungs and liver. Reduced Bmal1 expression was noted in hippocampus of LD-BPE mice, whereas DLAN-FA group increased Bmal1 and Cry1 expression in cortex. Our data demonstrate that light at night modulates neuroimmune and circadian responses following repeated BPE exposures.
Improper disposal of contaminants in wastewater may adversely impact organisms across multiple biological levels, including exposure to pharmaceutical and personal care products (PPCPs). Venlafaxine (VFX), a frequently prescribed antidepressant, is a drug of concern due to its potential environmental and neurotoxic effects. The concentrations of VFX used in this study were selected to span a range relevant to both acute toxicological testing and higher-end environmental contamination scenarios. Higher concentrations may occur in wastewater effluent, hospital discharge, or pharmaceutical manufacturing waste streams. This study investigated the effects of early-in-life (pre-and neonatal) VFX exposure on Caenorhabditis elegans at concentrations of 0, 9.37, 18.75, 28.12, or 37.5 mg/L. Neurobehavioral and cholinergic endpoints were assessed at the L4 stage to assess long-term neurotoxicity. Data demonstrated that worms exposed to the highest concentration exhibited increased locomotor activity, while pharyngeal pumping was elevated at both 9.37 and 37.5 mg/L. Acetylcholinesterase (AChE) activity was decreased at 9.37 and 28.12 mg/L. Early-life VFX exposure also altered social feeding behavior, with worms showing a preference for bacterial lawn border (18.75 and 37.5 mg/L) and enhanced group feeding (28.12 and 37.5 mg/L). These results indicate that neonatal VFX exposure induces behavioral and neurochemical changes in C. elegans, associated with disruption of the cholinergic system.
The beneficial therapeutic actions of cocoa (Theobroma cacao L.) in the treatment of cardiometabolic disorders, attributed to antioxidant and anti-inflammatory properties, are well established. Thus, it was of interest to determine the therapeutic potential of cocoa (Theobroma cacao L.) to inhibit Trichophyton rubrum, a dermatophyte frequently associated with infections, resulting in discomfort and psychosocial consequences. Cocoa emerges as a promising natural product attributed to its chemical composition which includes bioactive molecules, especially flavonoids, with recognized antioxidant, anti-inflammatory, and antifungal activities. In this investigation, L929 fibroblasts were exposed to T. rubrum and subsequently treated with cocoa extract at concentrations of 25, 50, 100, or 250 µg/ml for 24 h. Cocoa extract was previously solubilized in PBS buffer and characterized by HPLC to ensure quality and chemical composition of this natural product. Cell viability was assessed using MTT and PicoGreen assays, whereas oxidative stress parameters, including reactive oxygen species (ROS) and nitric oxide (NO) production, were determined using DCFH-DA assay and Griess reaction, respectively. Additional groups received only cocoa extract to determine cytocompatibility. Cocoa alone did not markedly affect cell viability, proliferation, levels of ROS or NO. In contrast, fungal infection induced cytotoxicity, enhanced dsDNA release (12%), and elevated NO levels (11%). Treatment with cocoa extract significantly increased extracellular dsDNA levels at 50 and 100 µg/ml and reduced NO production at all tested concentrations. Taken together, findings indicate that cocoa extract protects cells from T. rubrum-induced damage, suggesting this natural product be considered as a potential alternative for the management of dermatophytic infections.
Breast cancer remains a major threat to women's health worldwide, and exploring novel therapeutic targets is urgently needed. Inhibiting 5-lipoxygenase (5-LOX) showed promising potential in treating various malignancies. However, 5-LOX effects on breast cancer progression are largely unknown. Breast cancer cell lines (MCF-7 and MDA-MB-231) and nonmalignant breast epithelial cells (MCF-10A) were used in this study. The expression of 5-LOX was quantified by RT-qPCR and Western blot analysis. 5-LOX was upregulated by pCDNA3.1(+)-5-LOX transfection and inhibited using zileuton. The influence of 5-LOX modulation on cell apoptosis, invasion, and colony formation was determined using flow cytometry, Transwell invasion assay, and colony formation assay, respectively. Results demonstrated that 5-LOX mRNA and protein expression levels were significantly higher in breast cancer cells compared with nonmalignant breast epithelial cells. Transfection with pCDNA3.1(+)-5-LOX significantly upregulated 5-LOX expression, while zileuton, an anti-inflammatory leukotriene inhibitor of 5-LOX, treatment (400 μmol/L) markedly downregulated 5-LOX mRNA and protein levels. Treatment with zileuton significantly induced apoptosis in MCF-7 and inhibited in MDA-MB-231 cell invasion. Further, zileuton suppressed colony formation in both breast cancer cell lines. Data suggest that 5-LOX may serve as a potential therapeutic target for breast cancer, and zileuton warrants further investigation as a candidate anti-cancer agent.
The chemotherapeutic agent cisplatin for solid tumors frequently induces cancer-associated cachexia characterized by weight loss and decreased skeletal muscle mass. These adverse cisplatin-related symptoms are dose‑limiting, and the ability to counteract drug-initiated muscle atrophy in cancer-associated cachexia remains a pharmacological challenge. The aim of this study was to determine the protective efficacy of lobetyolin, a natural compound derived from Codonopsis pilosula, known to exert antioxidant, anti‑inflammatory, and anti‑apoptotic activities, against cisplatin-induced skeletal muscle wasting and subsequently elucidate a potential underlying molecular mechanism of action using a mouse model. Mice were injected with cisplatin (4 mg/kg, i.p. every other day, 4 doses in total) with concurrent oral lobetyolin (20 or 40 mg/kg daily) for 8 days. Lobetyolin inhibited cisplatin-induced reductions in body weight and grip strength, ameliorated gastrocnemius muscle atrophy, and preserved myofiber cross‑sectional area. Mechanistically, lobetyolin restored superoxide dismutase (SOD) activity and glutathione (GSH) levels while diminishing malondialdehyde (MDA) content in gastrocnemius muscle. Lobetyolin was found to activate the AKT signaling axis as evidenced by enhanced phosphorylation of AKT (Ser473) and FoxO3α (Thr32), which suppressed FoxO3α nuclear translocation and downregulated the E3 ubiquitin ligase Fbx32, thereby diminishing proteasomal protein degradation. Concurrently, lobetyolin normalized the Bax/Bcl‑2 ratio to inhibit myocyte apoptosis. These findings demonstrated that lobetyolin may be considered as a multi‑targeted therapeutic candidate to counteract oxidative injury, protein catabolism, and myocyte apoptosis initiated by cisplatin. Data suggest that lobetyolin's potential as a safe adjunctive agent against chemotherapy‑induced muscle wasting might involve AKT/FoxO3α pathway.
Lung cancer is a common cause of cancer-related mortality worldwide. Luteolin, a naturally occurring flavonoid compound, was reported to exert anticancer effects through various mechanisms: A549 cell non-small cell lung cancer (NSCLC) serves as a model system. The objective of this study was to investigate the effects of luteolin on apoptosis and autophagy using A549 cells. A549 cells were treated with varying concentrations of luteolin for 12, 24, or 48 hr, and cell viability was assessed using the CCK-8 assay to determine optimal concentrations and exposure times. After 24 hr incubation with 10, 40, or 160 μM luteolin, the influence of apoptosis and autophagy was determined using Hoechst 33,258 and MDC staining, respectively. Protein expression levels of Bcl-2, Bax, caspase-3, PI3K, AKT, and mTOR were measured by Western blot. Results demonstrated that luteolin significantly inhibited A549 cell proliferation in a concentration- and time-dependent manner. At all concentrations, luteolin significantly (1) promoted apoptosis and autophagy, (2) increased expression levels of Bax and cleaved caspase-3, (3) suppressed Bcl-2 expression, (4) enhanced autophagic vacuole formation, and (5) inhibited phosphorylation of PI3K, AKT, and mTOR pathways. Data suggest that luteolin inhibits proliferation of A549 cells by regulating apoptosis and autophagy.
Although oral antidiabetic agents are widely prescribed for management of type 2 diabetes mellitus (T2DM), their long-term mutagenic and carcinogenic safety remains insufficiently characterized. The aim of this study was to examine the genotoxic potential of empagliflozin, linagliptin, pioglitazone, and the fixed-dose combination (empagliflozin/linagliptin) using Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. Third-instar larvae from standard (ST) and high-bioactivation (HB) crosses, differing in cytochrome P450 enzyme activity, were chronically exposed to increasing concentrations of selected drugs. Empagliflozin, linagliptin, and their combination did not induce significant alterations in mutant clone frequency across all tested doses in either cross. In contrast, the highest concentration of pioglitazone (72 mg/ml) significantly elevated DNA damage, with lesions originating from both mutation and recombination in the ST cross, but almost exclusively from mutational events in the HB cross. These findings suggest that while empagliflozin and linagliptin present no apparent detectable genotoxic hazard under these tested conditions, pioglitazone displays a dose-dependent genotoxic effect. Data indicate the importance of systematic genotoxicity assessment in widely used antidiabetic medications to ensure patient safety.
Environmental contamination by pesticides is a major concern, and herbicides are the most widely applied plant protection products in agriculture. Nicosulfuron is a sulfonylurea herbicide widely used in post-emergence weed control in maize and is relatively mobile, which may increase its bioavailability in soil and water. These factors raise concern regarding effects on non-target organisms. The aim of this study was to investigate the effects of nicosulfuron on: (1) micronucleus induction in Vicia faba cells; (2) population growth rate of microalgae Raphidocelis subcapitata; (3) mobility of microcrustacean Daphnia magna; and (4) reproduction of the rotifer Brachionus calyciflorus. Nicosulfuron stimulated population growth of R. subcapitata after 72 h exposure. In D. magna, only the highest tested concentration (100 mg/L) produced a weak acute effect with 10% immobilization after 48 h. In B. calyciflorus, no clear concentration-dependent inhibition of reproduction was observed with highest concentration (15.36 mg/L) similar to control. In V. faba, nicosulfuron was cytotoxic at the highest concentrations tested and genotoxic, inducing micronuclei at 3.12 mg/L. To the best of our knowledge, this is the first report of genotoxic effects of nicosulfuron examined in a plant model. Because the concentrations tested were markedly higher than those typically reported in environmental waters, these present results need to be interpreted primarily as a hazard-based screening of biological responses rather than a direct environmental risk characterization. Overall, our findings advance knowledge of effects of nicosulfuron on non-target organisms and support the need for further studies under environmentally relevant exposure scenarios.
Sepsis is characterized by an imbalance between excessive oxidative stress and endogenous antioxidant responses, leading to multi-organ dysfunction. The aim of this study was to investigate the protective effect of argan oil (AO) against lipopolysaccharide (LPS)-induced oxidative stress, with particular focus on peroxisomal-related antioxidant implications in liver, brain, kidney and heart. Phenolic and pigment contents (chlorophylls and carotenoids) of AO and olive oil (OO) were quantified, and antioxidant capacities determined in vitro using DPPH, ABTS, and FRAP assays. Mice were supplemented daily with AO or OO for 28 days prior to challenge with intraperitoneal injection of LPS (5 mg/kg) to induce acute oxidative stress. Although OO exhibited a higher phenolic content and more potent in vitro antioxidant activity across all assays, in vivo outcomes noted tissue-specific antioxidant efficacy. Antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase) and glutathione levels as well as lipid peroxidation (malondialdehyde) were measured in the four target organs. LPS challenge initiated marked alterations in antioxidant defenses and increased oxidative damage in a tissue-dependent manner, with liver exhibiting the greatest response. AO supplementation efficiently mitigated LPS-induced redox imbalance, restoring antioxidant enzyme activities and limiting lipid peroxidation across organs, whereas OO displayed more variable and organ-dependent effects. These findings demonstrate that AO exerts significant in vivo antioxidant protection against LPS-induced oxidative stress despite lower in vitro antioxidant capacity than OO. Data show importance of tissue-specific and peroxisome-associated mechanisms in modulating oxidative stress responses and support AO as a promising nutritional strategy for attenuating sepsis-related organ dysfunction.
Methylmercury (MeHg) is a well-recognized toxicant, whereas microplastics (MP) are contaminants whose health effects continue to be explored. Evidence suggests that concomitant exposure to MeHg and polystyrene (PS) may enhance adverse outcomes in the gastrointestinal system. The aim of this study was to investigate the combined effects of MeHg and PS-MP on intestinal homeostasis, as well as systemic oxidative and inflammatory responses. A total of 64 rats with 30-days-old (n = 16 per group) were exposed to environmentally relevant doses of 0.5 mg/L MeHg and/or 0.2 mg/L PS-MP of 5 µm during 8 weeks. Co-exposure resulted in colon shortening, mucus depletion, and disruption of tight junction proteins, accompanied by macrophage infiltration and elevated pro-inflammatory cytokines. Structural and inflammatory changes were accompanied by gut dysbiosis, including altered microbial composition and reduced diversity indices. Biochemically, co-exposure amplified oxidative stress in the colon, with loss of free thiols and enhanced lipid peroxidation, while not markedly affecting glutathione-S-transferase activity. Systemically, combined treatment increased serum cytokines and induced genotoxicity. Although compensatory antioxidant responses were detected in blood, oxidative stress was evident in peripheral organs, particularly liver, kidneys, and heart. Taken together, these findings demonstrate that the intestine may be an early and sensitive target following co-exposure to MeHg and PS-MP, driving cytokine release into circulation and contributing to systemic injury. Our study provides novel in vivo evidence that combined PS-MP and MeHg exposure exacerbates some biological outcomes noted with individual contaminant exposure, indicating the importance of considering co-contamination scenarios in risk assessment of emerging pollutants.
Cellular responses to DNA damage play a crucial role in carcinogenesis, particularly in environmentally related cancers such as bladder cancer (BC). This is the ninth most frequently occurring cancer globally and most frequent in the urinary system. Polymorphic variants in genes encoding DNA repair proteins may interfere with their expression and/or activity. Consequently, modulation in an individual's gene response to exposure might occur resulting in greater susceptibility and lower survival rates in BC. Taking this into account, the study evaluated associations of single-nucleotide polymorphisms (SNPs) in base excision repair genes (XRCC1 rs25487 and OGG1 rs1052133) with BC susceptibility and prognosis. A total of 274 cases and 274 controls, matched on gender, age, and smoking status, were genotyped using DNA from peripheral blood. In susceptibility analyses, individuals with a family history of cancer who carried at least one reference allele (rs1052133, CC + CG) exhibited an increased risk of BC occurrence. For XRCC1, the TT + CC genotypes were associated with elevated risk for BC among pesticide-exposed individuals. Regarding prognosis, the rs1052133 CC genotype was associated with an enhanced risk of recurrence among smokers and female patients. Bioinformatic analyses indicated significantly higher expression of XRCC1 and OGG1 in bladder tissue and marked elevation in expression in tumors. These results suggest that gene-environment interaction might modulate risk of BC occurrence and subsequent prognosis.
Emerging contaminants are chemically diverse compounds that persist and migrate across environmental compartments, including water, soil, sediments, and food. Their removal from wastewater is particularly challenging, especially when present as mixtures, due to their persistence, low biodegradability, and formation of toxic byproducts. This study aimed to investigate the efficiency of photo-ozonation for degrading the emerging pollutants octocrylene, methylparaben, and benzophenone, individually and in binary and ternary mixtures, using ecotoxicological bioassays, addressing a knowledge gap still little explored in the literature. Aqueous solutions containing 100 µg/L of each compound were prepared and subjected to photo-ozonation, generating treated samples. Raw and treated solutions were assessed using the bioindicators Allium cepa and Eisenia fetida. In the plant assay, benzophenone exhibited cytotoxicity prior to treatment, while benzophenone, octocrylene, and their mixture displayed mutagenic effects. After photo-ozonation, increased cytotoxic and mutagenic responses were observed, and additional mixtures became toxic, attributed to the formation of transformation products. In the avoidance test, only the ethylparaben-benzophenone mixture produced toxicity to earthworms, although higher avoidance rates were noted in benzophenone samples following treatment. Taken together, photo-ozonation showed limited effectiveness in reducing ecotoxicity. Data demonstrated that treatment strategies need to consider mixture interactions and byproduct formation, reinforcing the need for optimized and environmentally safe advanced oxidation processes.
Sporotrichosis is an implantation mycosis induced by exposure to thermodimorphic fungi of genus Sporothrix, which affects both humans and animals, resulting in severe inflammatory responses. Purinergic signaling has been implicated in pathogenesis of fungal infections, recognized as a critical system for modulating immune responses and triggering effector mechanisms during sporotrichosis. Natural products have emerged as promising modulators of immune responses, particularly through their influence on purinergic signaling. Among these, farnesol, a sesquiterpene alcohol, demonstrated anti-inflammatory effects during sporotrichosis. However, the pathways involved in farnesol anti-inflammatory effects during S. brasiliensis infection remain to be determined. The aim of this study was to determine whether farnesol exerts a protective effect against S. brasiliensis-induced inflammatory damage via modulation of purinergic enzymes and purinergic molecules. Serum and splenic E-nucleoside triphosphate diphosphohydrolase (E-NTPDase) activity for adenosine triphosphate (ATP) was stimulated in infected rats compared to uninfected rats, while E-adenosine deaminase (E-ADA) activity was reduced. Serum and splenic extracellular levels of ATP and adenosine were elevated in infected rats compared to uninfected, as well as serum levels of interleukin 2 (IL-2) and interleukin-6 (IL-6). Farnesol diminished S. brasiliensis-initiated rise in serum and splenic E-NTPDase and elevation in levels of IL-2 and IL-6. In addition, farnesol blocked fungal-mediated fall in serum and splenic E-ADA activities and decreased alterations on extracellular levels of ATP and adenosine. Farnesol exerted protective effects involved stimulation of purinergic signaling enzyme activities and consequently regulation of purine metabolism, associated with elevated cytokine levels, thereby ameliorating immune response during sporotrichosis.
Melanoma and glioblastoma are among the most aggressive cancer types, presenting high recurrence rates, therapeutic resistance, and poor prognosis despite conventional approaches. In this context, nanotechnology has emerged as a promising strategy to overcome these limitations. The aim of this study was to (1) synthesize reduced graphene oxide (rGO) and its magnetic analogs (rGO∙Fe3O4), (2) determine the physicochemical characterization, and (3) examine the biological properties. The characteristics of the nanomaterials (NM) were analyzed using Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray diffraction (XRD), value stream mapping (VSM), and scanning electron microscope (SEM). These analyses showed the spectral and structural features of rGO and rGO∙Fe3O4. In vitro evaluation demonstrated that the treatments were more toxic to two cancer cell lines, A375 (melanoma) and U87MG (glioblastoma), than HaCaT (non-tumorigenic human keratinocyte). One mechanism of action may be associated with increased production of reactive oxygen species (ROS), as well as enhanced binding energy between rGO and rGO∙Fe3O4, and proteins involved in tumorigenesis. Molecular docking results indicated that rGO exhibited greater potential for interaction with selected proteins. These findings provide a foundation for further studies exploring the potential of rGO and rGO∙Fe3O4 as effective and biocompatible platforms for melanoma and glioblastoma cancer therapy.
Tobacco smoking may constitute a significant nonoccupational source of exposure to cadmium (Cd). Epidemiological studies found higher levels of Cd in urine in association with cigarette smoking suggesting that smoking might contribute significantly to metal body burden. In this study, a biokinetic model was used to predict renal cortex Cd and urine Cd levels associated with empirically based estimates of exposures to Cd in mainstream cigarette smoke. The biokinetic model predicted that smoking 10 cigarettes/day may elevate renal cortex and urine Cd levels 30-123% above the dietary baseline, depending upon intensity of puffing (International Organization for Standardization (ISO) or Health Canada Intense (HCI) smoking machine regimens). For ISO and HCI regimens, renal cortex Cd was predicted to increase 0.12 and 0.38 μg/g per cigarette smoked, respectively, with corresponding elevations in urine Cd of 0.0023 and 0.0069 μg/g creatinine, respectively. The biokinetic model predicted that HCI regimen smoking rates of 13 - 21 cigarettes/day might raise urine Cd levels by amounts observed in two epidemiological studies of smokers and never smokers (0.09-0.15 μg/g creatinine). Predictions based upon the CDBKM provide further support for plausibility of cigarette smoking contributing to the Cd body burden, which might be detectable as smoking-related increments in urine Cd levels.
Risperidone is an atypical antipsychotic drug clinically used to treat mood disorders, autism, and schizophrenia. Since risperidone is typically prescribed chronically for clinical use, it is important to determine potential side effects, such as toxicogenic consequences, which remain under-explored for this class of drugs. The main goal of this study was to (1) examine the genotoxicity attributed to risperidone using L929 murine fibroblasts with different standardized techniques (MTT, comet, and micronucleus (MN) assays) and (2) and oxidative potential by measuring levels of reduced glutathione (GSH) and carbonyl proteins, oxidative indices. Data demonstrated that risperidone exhibited a cytotoxic effect after 24 hr exposure, reducing cell viability by approximately 23% (compared to negative controls) at the highest concentration (500 µM). Standard alkaline comet (pH > 13) and MN assays noted the absence of genotoxic/mutagenic potentials after treatment with risperidone (100 and 500 µM), even in the presence of an exogenous metabolizing source (S9 fraction). However, the comet assay displayed the presence of the enzyme formamidopyrimidine DNA-glycosylase (FPG) in cells exposed to 500 µM risperidone resulting in a significant increase in levels of DNA damage, indicative of oxidative damage to the genome. This oxidative DNA damage was corroborated by reduction of the glutathione (GSH) levels, through modulation of GSH-dependent enzymes, and elevated levels of protein oxidation in cultures exposed to 500 µM risperidone. Data demonstrated that 500 µM risperidone exerted a cytotoxic effect on L929 cells accompanied by induction of DNA strand breaks generation of oxidative stress.
Although 2,4-D is one of the most widely used herbicides worldwide, herbicidal soil-mediated toxicity to higher plants and detritivores remains underexplored. This study aimed to determine the phyto-cytogenotoxic potential of soil artificially treated with the commercial herbicide U 46 BR (active ingredient: 2,4-D) using Allium cepa and Zea mays. Further, the feeding activity of Rhinocricus padbergi exposed to leaf litter treated with 2,4-D was measured. Concentrations spanning environmentally realistic to critical contamination levels (0 to 3.68 mg/kg) were tested. Root growth of A. cepa was significantly inhibited at 0.92, 1.84, or 3.68 mg/kg, while Z. mays was affected only at 3.68 mg/kg, indicating higher A. cepa sensitivity. Across all concentrations, A. cepa exhibited cytotoxic (reduced mitotic index) and/or genotoxic (increased chromosomal aberrations) responses. In R. padbergi, exposure to 2,4-D reduced assimilation and assimilation efficiency and increased fecal egestion. Considering soil physicochemical traits (clay texture, pH 6.9, moderate organic matter), our findings indicate the role of bioavailability in modulating toxicity. Collectively, the effects observed in primary producers and key detritivores demonstrate that environmentally relevant 2,4-D levels in soil might impair plant performance and feeding activity of soil invertebrates.
Per- and polyfluoroalkyl substances (PFAS) and micro/nanoplastics are widely detected and persistent contaminants present in natural waters. While considerable research has been conducted on effects of PFAS on freshwater fish, little is known regarding potential for adverse impacts on marine species. Similarly, much attention has been paid to potential impacts of microplastics, but less is known regarding effects of exposure to nano-sized plastics. The aim of this study was to investigate the potential for interactive effects between common models of PFAS (GenX) and nanoplastic particles (NP) by utilizing exposure of adult spotted seatrout to 4 treatments: Control, GenX, 50 nm fluorescing NP, and GenX + NP for 7 days, and then placed remaining fish in clean water for 7 more days. Exposure was conducted as a static renewal exposure in quadruplicate exposure tanks with four adult seatrout per tank. At the end of 7 days, fish were removed and sampled for analysis of impact. Our results indicate that GenX (1) accumulated in liver and brain of seatrout, (2) presence of NP increased concentration of GenX detected in these organs, and (3) combination of GenX+NP resulted in altered peroxisome proliferator-activated receptor (PPAR) expression profiles in brains of exposed fish. Data demonstrate that exposure to newer PFAS, such as GenX, in presence of NP may exert greater impacts than predicted from exposure to GenX alone. Further, adult pelagic marine fish might accumulate both PFAS and NP if exposed in the environment enhancing adverse environmental impacts.
As a consequence of the wide use of edible pulp of Annona squamosa in the food industry, substantial seed waste is generated. Repurposing this by-product into food applications offers a sustainable alternative with economic benefits. This study aimed to determine the antioxidant and chemopreventive potential of Conde seed flours (CSF) obtained from the film (CSFF) and almond (CSAF). Total phenolic compounds (TPC) and total flavonoid compounds (TFC) were analyzed by spectrophotometry and Ultra-Performance Liquid Chromatography (UPLC). Antioxidant activity assessed by ABTS•+ demonstrated higher values for CSFF (73.24 TE/g) compared to CSAF (4.21 TE/g). CSFF exhibited greater TPC (2.59 mg GAE/g) and TFC (2.43 mg CE/g), with p-coumaric acid (229.93 µg/g) as the predominant compound, representing approximately 93% of TPC. In contrast, CSAF exhibited lower TPC (0.57 mg GAE/g) and TFC (0.24 mg CE/g), with no detectable phenolic compounds. Protective activity against doxorubicin (DXR, 20 mg/kg bw)-induced DNA damage was assessed in Swiss mice using the micronucleus test. Both CSFF and CSAF displayed no cytotoxic or mutagenic effects. CSFF demonstrated significant chemopreventive potential, whereas CSAF exhibited antimutagenic effects at 3.5 and 14 mg/kg/bw/day. The higher phenolic content of CSFF, particularly p-coumaric acid, may contribute to superior DNA-protective effect, supporting CSF as a promising therapeutic functional food ingredient.
