Background Benzene (BZ) is a well-established hematotoxicant, and cigarette smoke (CS) is a major non-occupational source of BZ exposure. Although BZ and CS co-exposure commonly occurs in real-world settings, the mechanisms underlying their combined toxicity remain unclear. Objective This study investigated whether BZ and CS co-exposure aggravates hematotoxicity and explored the potential involvement of the aryl hydrocarbon receptor AhR-NLRP3 signaling pathway. Methods Sixty male Balb/c mice were divided into six groups: CON, BZ, CS, BZ + CS, BZ + CS + CH223191 (AhR inhibitor), and BZ + CS + MCC950 (NLRP3 inhibitor), and subjected to an 8-week sub-chronic exposure protocol. Peripheral blood parameters, bone marrow histopathology, AhR–NLRP3 signaling pathway-related protein expression, and circulating inflammatory cytokines (IL-1β, IL-6, and IL-18) were evaluated. Longitudinal outcomes and benzene × cigarette smoke interactions were analyzed using statistical models appropriate to the experimental design. Results BZ and CS co-exposure produced more pronounced hematological alterations than either exposure alone and was accompanied by aggravated bone marrow injury. Formal factorial analysis revealed significant benzene × cigarette smoke interactions for RBC and HGB, with interaction contrasts indicating greater-than-additive reductions. In contrast, no significant interactions were detected for WBC, NEUT, or PLT. Co-exposure also upregulated AhR, NLRP3, and cleaved caspase-1 (p20), and elevated circulating IL-1β, IL-6, and IL-18. Significant benzene × cigarette smoke interactions were observed for all three cytokines, with interaction contrasts indicating greater-than-additive increases. Pharmacological inhibition of AhR or NLRP3 attenuated hematological alterations, inflammatory cytokine elevations, and pathway-related changes. Conclusions BZ and CS co-exposure aggravates hematotoxicity, and AhR–NLRP3-related signaling may be involved in this process.
Background Maternal passive smoking (PS) during pregnancy remains a common environmental exposure associated with adverse perinatal outcomes. However, its effects on fetal lipid mediator profiles have not been fully characterized. Objective To investigate whether maternal PS during pregnancy is associated with alterations in umbilical cord blood lipid mediator profiles in term neonates. Methods We retrospectively analyzed umbilical cord blood samples from 56 term neonates, comprising 17 born to mothers with documented PS exposure and 39 born to mothers without PS exposure. Targeted lipid mediator profiling was performed using liquid chromatography–tandem mass spectrometry. Orthogonal partial least squares discriminant analysis, univariate analyses with Benjamini–Hochberg false discovery rate correction, receiver operating characteristic curve analysis, and exploratory multivariable linear regression were performed. Results Four lipid mediators showed nominal differences between the groups, with higher levels of 14,15-LTE₄, platelet-activating factor, and 13-HpODE and lower levels of oleoylethanolamide (OEA) in the PS-exposed group. However, none remained statistically significant after correction for multiple comparisons. OEA was subsequently evaluated in post-hoc exploratory multivariable analysis and remained associated with maternal PS exposure after adjustment for maternal pre-pregnancy BMI and diabetes mellitus. Conclusions This exploratory study identified several candidate cord blood lipid mediator signals related to maternal PS exposure, although none remained statistically significant after correction for multiple comparisons. These findings are hypothesis-generating but suggest that lipid mediator pathways involved in inflammatory and metabolic signaling may warrant further investigation in relation to prenatal tobacco smoke exposure.
The contamination of environmental systems by trace elements is an increasing concern in regions affected by intensive industrial and agricultural activities. These contaminants can infiltrate agricultural systems via irrigation with polluted water, resulting in food chain transfer and potential adverse effects on human health. In this study, water, sediment, soil, and vegetable samples were collected from the Mokolo River system in Lephalale, South Africa, and analysed for trace element concentrations. Samples were prepared, digested, and quantified using inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-optical emission spectrometry (ICP-OES). To ensure accuracy of the analytical method, standard reference materials (SRMs), including trace elements in natural water standard reference material (SRM 1640a), tomato leaves standard reference material (SRM 1573a), trace elements in soil standard reference material (SRM 2587), and standard reference material of soil (AMIS 0373), were analysed, yielding percentage recoveries within acceptable ranges. Concentrations of trace elements ranged from 0.00120 to 13.5 µg/L in water, 0.0169–157 µg/g in sediment, 0.0890–94.1 µg/g in soil, and 0.00420–54.7 µg/g in vegetable samples. Elevated concentrations of nickel (Ni), lead (Pb), chromium (Cr), and cadmium (Cd) were observed, frequently exceeding established international guideline limits. Evaluation of human health risk assessment (HHRA) showed that Target Health Quotient (THQ) and Hazard Index (HI) values exceeded 1 for both adult and children, suggesting possible non-carcinogenic risks arising from dietary exposure. The carcinogenic risk assessment revealed elevated values of incremental lifetime cancer risk (ILCR), particularly for Cr and Pb, with consistently higher estimated risk in children than adults. These results underscore the risk of trace elements accumulation in the agricultural systems and its potential implications for human health. Continuous monitoring and appropriate management strategies are therefore recommended to mitigate contamination and reduce exposure risks.
Preclinical safety evaluation of newly synthesized bioactive molecules is a crucial step in the drug development process. The acute and subacute oral toxicity of the synthesized 3-Hydroxyindolin-2-one derivative, 7-bromo-3-hydroxy-3-(2-oxo-2-(p-tolyl)ethyl)indolin-2-one (4b), was evaluated in BALB/c mice using a sequential-dose acute oral toxicity/tolerability assessment and a 28-day repeated-dose study. For the acute oral assessment, compound 4b was administered sequentially at 2000, 1000, and 300 mg/kg body weight, followed by a 14-day observation period. Mortality was observed at 2000 and 1000 mg/kg, whereas no mortality was observed at 300 mg/kg, and subacute toxicity was determined by oral doses of 15, 30, and 60 mg/kg per day for 28 days. To determine the body weight, hematological parameters, biochemical parameters, gross pathological examination, and histopathological evaluation of major organs were performed for the synthesized compound. No mortality was observed at 300 mg/kg during the acute observation period or during the 28-day repeated-dose study, and no treatment-related gross pathological changes were observed at the examined doses. Several statistically significant differences and deviations from the reference intervals were observed among individual hematological and biochemical parameters following repeated administration. However, these changes did not demonstrate a consistent dose-response pattern across sexes and were not accompanied by concordant clinical, gross pathological, or histopathological findings. Histopathological evaluation of selected organs in the vehicle-control and high-dose groups showed well-preserved tissue architecture, with no treatment-related lesions identified in the examined tissues. Together, these results indicate that the synthesized compound 4b caused no mortality or clear treatment-related hematological, biochemical, gross pathological, or histopathological effects at the administered doses.
Micro- and nanoplastics (MNPs), defined as plastic particles smaller than 5 mm and 1 μm, respectively, are ubiquitous environmental contaminants detected in human tissues and typically ingested through food and drinking water. No threshold for adverse health effects has been established. This narrative review synthesizes current evidence on the molecular mechanisms, interactions with Helicobacter pylori, and experimental findings from 2D and 3D gastric cancer models relevant to MNP-induced gastric carcinogenesis. Particle size, shape, polymer type, surface charge, and weathering status influence toxicity. Proposed mechanisms include oxidative stress, mitochondrial dysfunction, chronic inflammation, genotoxicity, gastric dysbiosis, and ferroptosis, mediated by dysregulation of NF-κB, Wnt/β-catenin, MAPK, PI3K/Akt/mTOR, and cGAS-STING signaling. Nanoplastics (~100 nm) may induce ferroptosis via Fosl1 and p53, whereas larger microplastic fragments may activate YAP signaling and promote proliferation. MNPs may also carry persistent organic pollutants and toxic metals and may act synergistically with H. pylori to potentiate mucosal damage. In conclusion, MNPs can plausibly promote gastric carcinogenesis through mechanisms demonstrated in experimental systems, but a causal role in human gastric cancer has not been established. Standardized analytical methods, environmentally realistic exposure models, and large-scale epidemiological studies are needed.
