Heavy metals in particulate matter (PM) contribute to oxidative stress, DNA damage, and inflammatory responses in skin cells. This study aimed to investigate the toxic effects of airborne heavy metals on human sebocytes, keratinocytes, and ex vivo skin. To this end, we collected sebum samples from indoor (n = 62) and outdoor (n = 40) workers in Shanghai and quantified the concentrations of 24 metals using inductively coupled plasma mass spectrometry (ICP-MS). Outdoor workers exhibited higher levels of cobalt (0.0004 vs. 0.39 mg/kg, 924.7-fold), arsenic (0.11 vs. 14.15 mg/kg, 134.7-fold), barium (0.70 vs. 20.24 mg/kg, 28.8-fold), and manganese (0.86 vs. 14.93 mg/kg, 17.3-fold) than indoor workers. Sebum-mimicking metal mixtures (SMMs), formulated to reflect the specific heavy metal profiles identified in the workers' sebum, were applied to human epidermal keratinocytes and sebocytes. Outdoor SMMs significantly reduced cell viability, increased lipid peroxidation, and induced DNA damage, as evidenced by the phosphorylation of histone H2AX (γH2AX) foci formation. Real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR) analysis revealed upregulated IL1A, IL1B, TNFA, IL6, and PTGS2 mRNA, primarily after treatment with outdoor SMMs. Further activation of the NF-κB and MAPK signaling pathways was also identified. This was corroborated in human scalp skin models, in which exposure to outdoor SMMs increased the expression of proinflammatory cytokines, including interleukin-1β (IL-1β) and IL-6, and decreased the expression of keratin 10. These findings highlight the detrimental effects of environmental heavy metals on skin homeostasis, providing a scientific basis for the development of antipollution skincare formulations.
Background:Hyperbilirubinemia is a prevalent manifestation of drug-induced liver injury, which can result in neurological complications in severe cases. Despite the extensive clinical application of Wenjing Decoction (WJD) over a millennium, there is a significant lack of systematic nonclinical safety evaluation data. Furthermore, the toxicity characteristics and mechanisms associated with long-term high-dose exposure remain unclear. Aim:This study seeks to conduct a systematic assessment of the toxicological characteristics of WJD via a 28-day repeated-dose toxicity investigation. Specifically, our focus lies in examining its impacts on hepatic and neurological functions, as well as elucidating its underlying molecular mechanisms. Methods:A bioinformatics approach was initially utilized to predict the potential molecular targets of WJD associated with hyperbilirubinemia. Subsequently, Kunming mice were randomized into either a control group or a high-dose WJD treatment group (18.75 g/kg, equivalent to 20 times the standard human daily dose). Animals received intragastric administration of the respective treatments daily for 28 consecutive days. A subset of animals was assigned to a recovery phase to monitor the reversibility of any observed effects. Serum biochemical parameters, including total bilirubin (TBIL) and unconjugated bilirubin (UCB), hepatic oxidative stress markers such as glutathione disulfide (GSSG) and malondialdehyde (MDA), and neurobehavioral performance (evaluated via pole climbing and shuttle box tests) were systematically measured. Furthermore, Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry were employed to analyze the expression levels of the Nrf2/Heme oxygenase-1 (HO-1) signaling pathway and related inflammatory cytokines. Finally, comprehensive histopathological examinations were conducted on both liver and brain tissues. Results:Bioinformatics predictions indicate that HO-1 is a key target. Animal experiments demonstrate that the administration of WJD results in a significant increase in serum TBIL and UCB in mice, exhibiting characteristics of nonhemolytic hyperbilirubinemia. Mild oxidative stress, characterized by increased GSSG and MDA levels, along with elevated ALT activity, occurs in the liver. This is accompanied by the activation of the Nrf2/HO-1 pathway and the upregulation of inflammatory factors such as IL-6, IL-1β, and TNF-α; however, no significant histopathological damage is observed. Regarding the nervous system, mice in the administration group show a decrease in anal temperature, impaired motor coordination, and abnormal avoidance behavior. Although the expression of HO-1 in brain tissue is downregulated, no organic lesions are detected in the brain. All of the aforementioned abnormal indicators can be reversed during the recovery period following drug withdrawal. Conclusion:Long-term and high-dose exposure to WJD can induce hyperbilirubinemia in mice by activating the hepatic Nrf2/HO-1 signaling pathway, as well as causing mild hepatic oxidative damage and neurobehavioral abnormalities. This toxic reaction is reversible, indicating that when WJD is used clinically for extended periods or at high doses, careful monitoring of bilirubin metabolism and related functional indicators is essential.
This study investigates the spatiotemporal distribution of organochlorine pesticides (OCPs) in the surface water (n = 60) of Shitalakshya River, Bangladesh, by an optimized and validated LLE-GC-ECD method by calibration (0.10-5.00 µgL-1), linearity (R 2 = 0.995-0.999), recovery (80.11%-117.10%), precision, specificity, selectivity, LODs (0.0009-0.0026 µgL-1), and LOQs (0.0027-0.0079 µgL-1). Among the targeted OCPs, α-BHC (0.01-0.19 µgL-1), δ-BHC (0.01-0.27 µgL-1), chlordane (0.01-0.23 µgL-1), endosulfan (0.01 and 1.56 µgL-1), 4,4'-DDE (0.01-2.14 µgL-1), dieldrin (0.03-0.58 µgL-1), endrin (0.01-2.96 µgL-1), 4,4'-DDD (0.01-4.07 µgL-1), endrin aldehyde (0.01-3.72 µgL-1), 4,4'-DDT (0.01-0.02 µgL-1), and endosulfan sulfate (0.03-2.05 µgL-1) were detected with varying frequencies. These levels were below the international guideline values, except 4,4'-DDE in Kanchon (2.14 μgL-1), dieldrin in Kanchpur (0.10 μgL-1), Atlapur (0.12 μgL-1), Ghorashal (0.45 μgL-1), Charshindur (0.58 μgL-1) and Kapasia (0.03 μgL-1), endrin in Kapasia (2.96 μgL-1), 4,4'-DDD in Kalagachhia (1.63 μgL-1), Narayanganj (0.69 μgL-1), Nabiganj (1.95 μgL-1), Ichakhali (1.05 μgL-1), Kanchon (0.57 μgL-1), Atlapur (1.02 μgL-1), Ghorashal (2.51 μgL-1), and Charshindur (4.07 μgL-1). The occurrence of OCPs exhibited pronounced spatiotemporal variation, with the highest concentrations and detection frequencies observed during the dry seasons (L. autumn, autumn, winter, and spring), indicating reduced dilution and possible remobilization from contaminated sediments. Multivariate statistical analysis revealed distinct sources, with endosulfans and BHCs dominating at Kanchon, whereas dieldrin, endrin, and chlordane were more strongly associated with Ghorashal and nearby locations, suggesting localized anthropogenic inputs and legacy pollution sources. While risk is generally low, specific exceedances (H q > 1) were observed in L. Autumn 2022 for 4,4'-DDD, indicating a localized noncarcinogenic hazard. While the immediate screening-level risks are low across most seasons, the high chemical persistence and bioaccumulation over time warrant continued monitoring and proactive water management.
Landfills serve as a significant source of microplastics (MPs) contamination, affecting the surrounding air, water, and agricultural soils. This study examined the seasonal variation of MPs in leachate, river water, and soil at Sisdole (old) and Banchare Dada (new) landfill sites (LFSs). MPs greater than 90 μm were enumerated using a stereomicroscope, and polymer identification was performed on a representative subset of particles using micro-Fourier transform infrared (FTIR) spectroscopy. Average MPs concentrations were higher at the new landfill, with values of 56 ± 07 MPs/L at Banchare Field and 44 ± 27 MPs/L at Banchare Tank, compared to 28 ± 11 MPs/L at Sisdole Pond in the old landfill. In river water, MPs increased downstream: 17 ± 12 MPs/L at Sisdole Upstream, 28 ± 22 MPs/L at Sisdole Downstream, and 34 ± 06 MPs/L at Banchare Downstream. Soil contamination was highest at Sisdole (351 ± 173 MPs/100 g), followed by Banchare (214 ± 70 MPs/100 g) and Banchare-Sisdole (157 ± 48 MPs/100 g). Statistical analyses, including a paired t-test for river water and a two-way ANOVA for soil samples, showed significant differences in MPs concentrations between the monsoon and premonsoon seasons in both river water and soil. Fibers were the dominant form of MPs in leachate, river water, and soil, whereas fragments were mainly within the 90-500 μm size range and fibers within the 1000-5000 μm range. Polyethylene terephthalate/polyester (PET/PES) accounted for 50% of the identified polymers, followed by polypropylene (PP, 20%), polyethylene (PE, 10%), and other polymers (20%). The polymeric composition suggests that textiles and degraded plastic packaging are the possible sources of MPs. Overall, the study identifies landfill-derived MPs as a possible source of pollution in nearby river and agricultural lands, underscoring the urgent need for measures, such as leachate treatment and improved landfill management practices by the relevant authorities.
Turmeric (Curcuma longa), a widely used botanical in traditional medicine, has gained global attention for its therapeutic potential, particularly due to its components including curcumin. While its pharmacological benefits are extensively documented, concerns regarding its safety profile and potential toxicity have emerged, especially with high-dose supplementation and long-term use. This narrative review aims to critically evaluate the toxicological evidence and safety considerations surrounding turmeric and its main components. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar, covering studies published up to October 2025. In vitro and in vivo studies were carried out to capture a broad spectrum of toxicological data. Toxicological profile of turmeric is influenced by dose, formulation, and metabolic context. Most turmeric-based preparations exhibit low acute toxicity and minimal genotoxic or mutagenic effects under standard conditions. However, high concentrations or certain formulations, particularly crude (unfractionated) extracts, have been reported to induce oxidative stress and DNA damage in vitro, while some nanoparticle systems show mutagenic potential under metabolic activation conditions. In vivo studies generally report favorable safety outcomes, especially for standardized and bioavailable formulations, although some evidence of liver enzyme alterations and histopathological changes has been observed at supratherapeutic doses. Mechanistic insights implicate oxidative stress, mitochondrial dysfunction, and p53-mediated pathways in the observed toxic effects. Turmeric and its components are generally safe when used at recommended doses and in well-designed formulations. However, high-dose or prolonged use may pose hepatic and genomic risks. Refining safety thresholds through harmonized methods and human-relevant models will be the key to guiding their safe and effective clinical application.
Immunogrit is a traditional Ayurvedic medicine prescribed to patients for their general well-being. In this study, Immunogrit was evaluated for its subacute (28 days) repeated oral dose toxicity in male and female Sprague-Dawley (SD) rats of similar age and body weight following OECD 407 guidelines under Good Laboratory Practices compliance. Mutagenic potential of Immunogrit was also evaluated through Ames assay following OECD 471 guidelines. Phytochemical profiling of the Immunogrit was performed using ultraperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight(UPLC/MS-QToF) tandem mass spectrometer. UPLC/MS-QToF analysis of Immunogrit identified 74 phytochemicals, well known for their health benefits. Male and female specific pathogen-free SD rats were orally gavaged to 100, 300, and 1000 mg/kg body weight/day of Immunogrit, over a period of 28 days, with two additional groups for a recovery phase of 14 days. No incidence of mortality, morbidity, or abnormal clinical signs was observed in the Immunogrit-exposed animals. Body weight, behavioral, and food consumption habit were found to be normal throughout the study period. Immunogrit exposure did not induce ophthalmic, neurological, functional, hematological, biochemical, and histopathological irregularities in animals over a period of 28 days. Latent incidence of toxicity was also not observed in the recovery group male and female rats kept under observation for an additional 14 days' post-Immunogrit exposure. Ames test of Immunogrit and its S9-treated fraction in Salmonella typhimurium strains TA1535, TA1537, TA98, and TA100, and Escherichia coli WP2uvrA did not show any induced mutagenic potential, up to the highest dose tested. In conclusion, Immunogrit was found to be nonmutagenic and showed a "no-observed-adverse-effect-level" (NOAEL) of 1000 mg/kg body weight/day in male and female SD rats.
Angiogenesis is crucial for tissue repair and the treatment of ischemic diseases, yet effective small-molecule proangiogenic agents are lacking in clinical practice. Chalcone-based compounds are of interest due to their diverse biological activities. This study aimed to synthesize and evaluate the proangiogenic potential of a series of novel chalcone derivatives and to elucidate their structure-activity relationship (SAR) using computational chemistry. We synthesized and tested six chalcone derivatives (1a-1f), with compound (E)-1-(3,4-dimethoxyphenyl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one (1c) exhibiting the highest activity. In the zebrafish model, treatment with 1c significantly increased the formation of branch points and vessel outgrowth in the subintestinal vein (SIV) (number of branch points: 1c group 2.28 ± 0.19, control group 0.79 ± 0.17; p < 0.001). Using Tg(fli1:egfp) transgenic zebrafish, we observed that 1c dramatically promoted the remodeling of the caudal vein plexus (CVP), leading to a significant increase in the number of intercapillary spaces (1c group 16.3 ± 1.9, mock group 11.6 ± 2). Mechanistically, real-time polymerase chain reaction (RT-PCR) results showed that 1c treatment upregulated the expression of key angiogenic genes cadherin 5 and neuropilin 1a, while downregulating the expression of fms-related receptor tyrosine kinase 1. Furthermore, the chick embryo chorioallantoic membrane (CAM) assay confirmed that 1c effectively induced vascular network formation. Computational chemistry analyses (DFT, MESP, and FMO) were highly consistent with the biological activity. 1c possessed the highest electrophilicity index (ω), chemical potential (μ), and electron transfer capability (ΔN), as well as the strongest electrophilic site (V s,max), which explains its superior biological activity. This study confirms the potent proangiogenic activity of chalcone derivative 1c, providing a promising lead compound for the development of novel small-molecule therapeutics targeting vascular dysfunction diseases.
Despite scientific evidence and government actions aimed at reducing air pollution, it remains a major public health issue in large urban centers, compromising human health, particularly among the most vulnerable populations, including the elderly. Polyphenolic compounds are believed to have antiaging effects, reducing DNA damage and exhibiting anti-inflammatory and antioxidant properties. The polyphenol resveratrol (Resv) has demonstrated protective effects in the lungs against harmful stimuli in adult mice; however, few studies have extended these investigations to elderly animals, which have reduced antioxidant responses. This study aimed to evaluate the effects of Resv on the lungs of 15-month-old mice exposed to diesel exhaust (DE). Animals were exposed to 1200 & micro;g/m3 of PM2.5 over 30 consecutive days. Resv (1200 & micro;g/m3) was administered for 40 days, beginning 10 days before DE exposure. We evaluated the inflammatory profile in bronchoalveolar lavage fluid (BALF) and serum; quantified macrophages; and assessed antioxidant enzymes (glutathione peroxidase [GPx], glutathione reductase [GR], glutathione-S-transferase [GST], and copper/zinc superoxide dismutase [Cu/Zn SOD]), 8-OHdG, 8-iso-prostaglandin F2 alpha (8-isoprostane), collagen and elastic fiber content, and sirtuin protein levels (Sirt1, Sirt2, and Sirt6) in the lung parenchyma. Resv administration increased GR and Sirt1 levels and decreased Sirt2 levels. DE caused inflammatory changes in BALF and lung tissue, increased 8-OHdG and 8-isoprostane levels, and modulated antioxidant enzymes, sirtuins, and lung collagen. Resv administration after DE exposure did not significantly alter 8-OHdG, antioxidant enzymes, sirtuins, or collagen levels in the lungs, but it reduced BALF cellularity and IL-1 beta and 8-isoprostane levels. Our data suggest moderate protective effects of Resv in aged lungs exposed to DE.
Exposure to toxic metals contributes to the growing burden of noncommunicable diseases (NCDs), yet evidence from sub-Saharan Africa remains limited. This hospital-based cross-sectional study assessed heavy metal (arsenic [As], cadmium [Cd], lead [Pb]) exposure levels and their association with health risks in adult diabetic and hypertensive patients in Cameroon. It involved 178 participants (39 diabetics, 78 hypertensives, 61 comorbid), and the urinary metals were quantified using atomic absorption spectrophotometry and normalized to creatinine. Serum oxidative stress biomarkers including glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and paraoxonase 1 (PON1) were measured. Health risk indices including estimated daily intake (EDI), chronic daily intake (CDI), hazard quotient (HQ), hazard index (HI) and cancer risk (CR), were computed. Proportion contribution trend (PCT), receiver operating characteristic (ROC) and ordinary least squares (OLS) regression were applied for risk and predictive analyses. Diabetic patients exhibited significantly higher (p < 0.05) urinary Cd (5.21 ± 0.83 μg/g creatinine) and Pb (0.66 ± 0.12 μg/g creatinine) levels compared with hypertensive and comorbid patients. GSH levels were markedly lower (p < 0.05) in diabetics than in hypertensives. Although HQs and HIs were < 1, diabetics recorded the highest HI (2.73 × 10-1 ± 2.27 × 10-2; p < 0.05), indicating increased chronic exposure risk. CR values for As and Cd exceeded USEPA thresholds (10-6), with diabetics showing the greatest risk. PCT identified Cd as the dominant contributor to HI across groups. ROC analysis showed that As CDI moderately predicted CR in diabetics (AUC = 0.604; p = 0.047). OLS regression revealed water source and residence as significant determinants of As and Pb exposure. Summarily, diabetic individuals demonstrated disproportionately higher heavy metal exposure and associated carcinogenic risk, largely driven by Cd. Integrating environmental biomonitoring into NCD management is essential to mitigate heavy metal-related health burdens in Cameroon.
Microplastics (MPs) and heavy metal mercury (Hg) have drawn global surveillance as major contaminants due to their toxic effects on aquatic organisms. The individual effects of both contaminants have been extensively characterized; however, their coexposure effects remain insufficiently explored. As aquatic organisms are increasingly exposed to multiple pollutants simultaneously in natural environments, this investigation explored the combined effects of polyamide MP (PA-MP) and Hg on Nile tilapia (Oreochromis niloticus) fingerlings, focusing on survival, growth, hematological balance, tissue structure, GH/IGF axis regulation, and immune-antioxidant responses. Over a 42-day trial, 240 Nile tilapia fingerlings were allocated into four triplicated treatments: control (no PA-MP or Hg), PA-MP (10 mg/L), Hg (0.03 mg/L), and PA-MP + Hg (10 mg/L + 0.03 mg/L), with 20 fingerlings per tank. The coexposure group showed increased MP accumulation and mortality, suppressed growth indicators, and substantial shifts in blood physiology, including elevated glucose (126.83 ± 2.40 mg/dL) and lowered hemoglobin (9.45 ± 0.85 g/dL), along with higher cellular and nuclear abnormalities. The histoarchitectural assessment identified severe structural deformities in the gills, intestine, liver, and kidney of coexposed fish compared to control and individual contaminants. At the transcriptional level, the expression of growth hormone-secreting gene (gh) in the pituitary and insulin-like growth factors (igf-1 and igf-2) in the liver showed a significant downregulation under coexposure treatment. Moreover, coexposure to PA-MP and Hg induced hepatic oxidative damage by affecting antioxidant defense, as evidenced by altered activity of superoxide dismutase (sod) and catalase (cat), and simultaneously modulated immune responses by significantly upregulating interferon-γ (ifn-γ) and tumor necrosis factor-α (tnf-α) while downregulating interleukin-1β (il-1β), indicating an oxidative-inflammatory response. These outcomes collectively underscore that MP and Hg coexposure aggravates both systemic and molecular impairments in Nile tilapia, resulting in weakened molecular responses, impaired physiological functions, and decreased survivability.
As a heavy metal and alpha emitter, uranium U(VI) presents chemical and radiological toxicity risks. Its toxicity particularly targets the kidneys in the event of intoxication, but the detailed study mechanisms leading to uranium-induced renal failure have not yet been studied based on the adverse outcome pathway (AOP) approach. Using a well-specialized in vitro model of renal proximal tubule epithelial cells (hRPTEC TERT1), this research aims to contribute to the development of the AOP of kidney toxicity. After identifying the U(VI) concentrations that induce deleterious effects (apoptosis and necrosis/cytotoxicity), key events linked to oxidative stress, apoptosis, survival, inflammation, and kidney toxicity are studied at the gene and protein levels. Apoptosis (Caspase 3/7 activity) is induced starting from exposure to 300 μM and necrosis (LDH assay) from 500 μM with a rate of 60%. hRPTEC cells have an IC50 of 420 μM after 48 h U(VI) exposure. Uranium induces an early 2-fold rise in ROS production, and an antioxidant response was observed accordingly. Cell survival signaling appeared to be enhanced at 100 μM, while higher concentrations (> 300 μM) induced a marked inflammatory response, with increased levels of TNFα (6,5-fold), IL-6, and IL-18, leading to a 16% increase in caspase 3/7 at 300 μM and LDH at 500 μM. A slight increase of 22% in the KIM-1 protein level is observed at 500 μM, and limited changes occurred for other nephrotoxicity biomarkers. In conclusion, this exploratory work generated a multiplex panel detailing the key events in the AOP of uranium-induced renal failure (Graphical Abstract). This panel features a human phenotype of renal proximal tubule epithelial cells, the preferential target of uranium in the kidney, while also considering the dose-dependent effects.
Microplastics, as emerging pollutants, are ubiquitously present globally and pose significant threats to both ecosystems and human health. These pollutants not only exert direct toxicity on the environment and living organisms but also influence the toxicity of other pollutants through mechanisms such as adsorption and carrier effects. The health risks of microplastics are multifaceted and complex, involving cellular toxicity, immune dysfunction, and impairments to neurological, endocrine, and reproductive systems. This review summarizes the combined toxic effects of microplastics and heavy metals, organic pollutants, plastic additives, antibiotics, and viruses, exploring their potential mechanisms and influencing factors. The paper suggests that future research should focus on simulating exposure scenarios, examining the long-term effects of exposure, and understanding the health consequences of combined exposures. This will provide new perspectives on the toxic effects of microplastics on the environment and organisms, enhance public awareness of their potential harm, and better address the impact of microplastic pollution on ecosystems.
Microplastic (MP) contamination is an emerging threat to freshwater ecosystems and food security. The objective of this study was to provide a comprehensive baseline assessment of MP abundance, polymer composition, and tissue-specific distribution across five organs (gut, gills, liver, gonads, and muscle) of two economically vital species Labeo rohita and Pangasius pangasius, in Udupi, Karnataka, India. MPs were detected in 100% of specimens, with higher mean (± standard deviation) abundances of 58.27 ± 10.48 particles per individual (particles ind-1) in L. rohita and 42.40 ± 5.40 particles ind-1 in P. pangasius. While L. rohita showed preferential accumulation in the gills and gut, in P. pangasius, MPs were more uniformly distributed across organs. Fibers dominated the assemblage (97.68%), with polypropylene and polyester identified as the primary polymers via Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) analysis. We conclude that the pervasive presence of MPs across all tissues, particularly the high accumulation in edible muscle and reproductive gonadal tissue, signals an urgent ecological risk and a direct pathway for human dietary exposure. The detection of MPs in gonadal tissues, while not yet linked to observed physiological impairment, identifies a potential reproductive risk and highlights a critical area for future histological and toxicological investigation. These findings establish a baseline for assessing the long-term health of local fisheries.
Background:Xylopia aethiopica (XAE) fruit (Ethiopian pepper) is a culinary spice widely used in African countries. It has numerous biological properties including potent anticancer properties; however, there is a lack of data on its safety, which justifies this study. Methods:Animals were administered a unique dose of 2000 mg/kg for the acute (14-day) toxicity and three doses (75, 150, and 300 mg/kg BW) of the subchronic (90-day) oral toxicity of ethanol dry fruit of XAE extract guideline numbers 423 and 408, respectively. Behavioral, morphological (body weight and relative weight of the organs), biochemical, hematological, and histological parameters of toxicological interest were evaluated with organs, such as the lung, liver, kidney, breast, and testes, just to name a few. Results:An LD50 > 2000 mg/kg was found after an acute exposure to XAE in young female rats. After 90 days of administration, XAE induced no significant changes in body weight and relative weights of the organs. In both female and male rats, no significant changes were observed in the tested biochemical parameters (creatinine, total proteins, triglycerides, total cholesterol, HDL, LDL, ALT, AST, and urea), except for the bilirubin levels, which slightly decreased in males at a dose of 300 mg/kg BW. No change was observed in the histological sections of organs of interest in toxicology (spleen, lungs, kidneys, liver, and heart) as well as in the reproductive organs (vagina, uterus, and ovary for females and testes, seminal vesicle, prostate, and epididymis for males). A significant decrease was observed in the level of hematological parameters, such as platelet levels in both female (p ≤ 0.001) and male (p ≤ 0.01) Wistar rats when compared to the control. This decrease in platelet concentration observed in experimental rats suggests that XAE may induce thrombocytopenia, possibly through an adverse effect on thrombopoiesis. Conclusion:Taken altogether, the observations therefore showed that long-term administration of XAE dry fruit extract might induce thrombocytopenia and anemia, particularly at higher doses, warranting caution regarding long-term use.
Sunscreens and parabens contaminate agricultural areas worldwide; however, the effects of these micropollutants in mixture on cultivated plants have not yet been reported. This study evaluated the cellular and systemic toxicity induced by octocrylene (OC), methylparaben (MeP), and butylparaben (BuP), individually at concentrations of 10, 50, 100, and 500 ng·L−1, as well as by equimolar binary mixtures (1:1) of OC with MeP and OC with BuP, in seeds of Cucumis sativus L. and Lycopersicum esculentum L., and in roots of Allium cepa L. bulbs. The OC + MeP mixtures induced H2O2 accumulation, whereas the OC + BuP mixtures promoted lipid peroxidation in the root meristems of A. cepa, resulting in significant mitodepressive, aneugenic, and clastogenic effects. The OC + BuP combination markedly reduced root growth in the three evaluated species and, in onion, caused mitotic indices below 50% compared to the control, demonstrating severe cytotoxicity to the meristems. In contrast, the OC + MeP combination stimulated root growth in cucumber, tomato, and onion. However, although significantly longer, the formed roots exhibited greater susceptibility to breakage than the control, indicating that growth predominantly associated with cell elongation, without concomitant cell proliferation. The interaction between the compounds was characterized as synergistic for OC + MeP and additive for OC + BuP, with BuP being the main determinant of mixture toxicity. Thus, mixtures of OC + MeP and OC + BuP may impair the early establishment of crops by affecting root system functionality, delaying or inhibiting root development, and altering root structural stability. These effects indicate that the presence of these micropollutant mixtures in contaminated agricultural soils may negatively influence plant development and the agronomic performance of cultivated plants.
The present study evaluated the acute and subacute oral toxicities of a chloroform extract from Pseudomonas fluorescens DS17R in Wistar rats to support its safe application as a biocontrol agent. For acute toxicity assessment following OECD Guideline 423, female Wistar rats (n = 3 per step) received single oral doses of 300, 2000, or 5000 mg/kg body weight (bw) and were observed for 14 days. For subacute toxicity, female rats (n = 5 per group) received daily oral doses of 0 (control), 57.5, 115, 230, or 460 mg/kg bw for 28 days, after which hematological, biochemical, and histopathological analyses were performed. Acute toxicity testing revealed no mortality at 300 or 2000 mg/kg bw, but 50% mortality at 5000 mg/kg bw, yielding a median lethal dose (LD50) of 4574 mg/kg bw, classifying the extract as practically nontoxic (OECD Category 5). Subacute 28-day oral exposure induced dose- and time-dependent physiological and biochemical responses. Body weight showed a biphasic pattern, with a significant increase at 57.5 mg/kg bw and reductions at ≥ 115 mg/kg bw, while feed intake was transiently suppressed. Hepatic enlargement was observed at 115-460 mg/kg bw, accompanied by elevated alkaline phosphatase and mild AST increase; histology revealed sinusoidal dilation and leukocyte infiltration. Splenomegaly, lymphopenia at 230 and 460 mg/kg bw, microcytosis, anisocytosis, and thrombocytosis reflected hematopoietic and immune modulation. Renal stress was evidenced by hyponatremia, hypokalemia, hypochloremia, hypercalcemia, and decreased phosphate at doses ≥ 57.5 mg/kg bw, with mild tubular alterations. Lipid remodeling included increased triglycerides and HDL, with decreased LDL at doses ≥ 115 mg/kg bw. Overall, the extract induced adaptive metabolic and redox-mediated responses without irreversible organ damage, supporting its potential safe use as a microbial biocontrol agent under the tested conditions.
Renogrit is a prescription medicine developed by employing the traditional knowledge of Ayurveda for the management of kidney disorders. To support its extensive clinical investigations, Renogrit requires robust nonclinical safety assessments. Accordingly, in this study, in vitro mutagenicity assay and in vivo subacute toxicity were conducted as per the Organization for Economic Co-operation and Development (OECD) guidelines. Mutagenic potential of Renogrit was tested using Salmonella typhimurium and Escherichia coli uvrA tester strains in the presence and absence of metabolic activation. DMSO stock solution of Renogrit was assessed at 0.05, 0.15, 0.5, 1.5, and 5.0 mg/plate concentrations, in triplicates, along with the vehicle (DMSO) control and respective positive controls. The revertant colonies were counted after 64- to 72-h incubation period at 37°C. Renogrit was administered to Sprague Dawley (SD) rats by oral route for 28 consecutive days, at the dose levels of 100, 300, and 1000 mg/kg/day. Animals were monitored for all major toxicological parameters, such as morbidity and mortality, clinical signs, body weight, feed consumption, ophthalmological examinations, and functional observational battery (FOB) assessments during the live phase of the study. At study termination, all animals were subjected to hematological analysis, clinical chemistry analysis, examination of organs for gross pathology, and histopathological investigations. The revertant colonies counted in the Renogrit-incubated plates were not significantly increased when compared to vehicle-treated plates, thereby signifying its nonmutagenic potential. Additionally, the subacute toxicity study revealed no toxicologically significant changes attributable to Renogrit administration up to a dose of 1000 mg/kg/day. In conclusion, Renogrit was found to be a nonmutagenic at the evaluated concentrations, and its No Observed Adverse Effect Level (NOAEL) was determined to be 1000 mg/kg/day. The study outcomes provide future nonclinical safety assessments of Renogrit and its detailed clinical evaluation.
Objective:Zylaria comprises a blend of botanical components, including Xylaria Nigripes (mycelium), Cuscuta Chinensis (seed) and Panax Notoginseng (root). This study aimed to evaluate the potential toxicity of Zylaria when administered orally (via gavage) to Sprague Dawley (SD) rats for 90 days continuously and examine any delayed toxicity after a minimum recovery period of 28 days post-treatment cessation. Methods:One hundred SD rats of both sexes were divided into six study groups: four main groups with 10 rats of each sex receiving different doses of Zylaria (0, 1000, 2750 and 4500 mg/kg body weight per day) and two recovery groups with five rats of each sex receiving either the vehicle control (Milli-Q water) or high-dose Zylaria. Throughout the study, animals were monitored daily for general behaviour, body weight fluctuations and clinical signs. Upon completion of the treatment period, haematological, coagulation, clinical chemistry, thyroid hormone analyses and histopathological examination of organs were conducted. Results:Oral administration of Zylaria at tested concentrations did not induce any adverse events on general health, body weight, relative organ weights, or haematological, coagulation, clinical chemistry, and thyroid hormone parameters. Histopathological examination demonstrated no significant structural alterations in organs, even in animals treated with high doses of Zylaria. No test item-related effects were observed during the 28-day recovery period after cessation of the treatment. Conclusion:The study concluded that Zylaria treatment for 90 days does not lead to toxicity, even at doses up to 4500 mg/kg bw/day, indicating its safety for use.
Males with prostate cancer exhibit substantial mortality and metastasis; however, few effective treatment strategies are available for advanced prostate cancer. Phillyrins (PHNs) are lignan glycosides that have been reported to exhibit diverse biological activities, including potential anticancer effects. We aimed (1) to assess the effect of PHN on PC3 prostate cancer cells and (2) to examine cellular responses associated with its activity. To assess the effects of PHN, it was exposed to various concentrations of PHN (1, 2.5, and 5 μM) for 24 h. A wound-healing assay was performed to evaluate cell migration. Western blotting and immunofluorescence were used to investigate the expression of adenosine monophosphate-activated protein kinase (AMPK)-associated proteins and transcription factors involved in epithelial-mesenchymal transition (EMT). PHN exposure was associated with reduced migratory capacity of PC3 cells under noncytotoxic conditions. PHN exposure was associated with decreased α-smooth muscle actin, Snail, and Slug expression while increasing E-cadherin expression. Sirtuin 1 (SIRT1) and nuclear respiratory factor 1 (NRF1) protein levels were upregulated in PHN-treated cells, accompanied by changes in AMPK protein expression. Pharmacological inhibition with Compound C attenuated PHN-associated changes in EMT-related marker expression in PC3 cells. Thus, PHN exposure may influence EMT-associated phenotypes in PC3 cells, potentially involving AMPK-associated signaling.
Rapid industrialization and urbanization have led to the unchecked discharge of toxic metals, posing serious threats to ecosystems and public health. This study analyses scientometric data on toxic metal pollutants, covering publications from 1992 to 2024. About 220 documents (183 research articles and 37 reviews) were extracted from Web of Science using BibExcel and VOSviewer to explore global research trends on metal toxicity, focusing on lead (Pb), mercury (Hg), cadmium (Cd), arsenic (As), chromium (Cr), scandium (Sc), beryllium (Be), and aluminum (Al). A notable rise in research since 2000 reflects growing awareness of metal-related risks. China leads in publication output, while the United Kingdom ranks highest in citation impact. The National Natural Science Foundation of China (NSFC) played a key role in advancing high-impact studies. It prioritizes funding for research in environmental toxicology and health effects of pollutants, environmental exposure and health effects of emerging toxic substances, toxicology of micro-/nanomaterials, toxicological mechanisms and health impacts of atmospheric fine particulate matter (PM2.5), and prevention and control of hazardous chemicals. Keyword co-occurrence and cluster analysis highlight themes such as bioremediation, nanomaterials, and detection technologies. Key research gaps include limited data on rare earth metal toxicity and the effects of chronic low-dose exposures. This study underscores the need for integrated global efforts in detecting, remediating, and mitigating risks.
