Journal of Environmental Science and Health Part C-Toxicology and Carcinogenesis最新文献

Background: Due to their simplicity, eco-friendliness, availability and non-toxicity, the greener fabrication of metal and metal oxide nanoparticles has been a highly attractive research area over the last decade. Aim: This study aimed to assess the antioxidant and antimicrobial activities of the green synthesized zinc oxide nanoparticles (ZnO-NPs) using an aqueous leaf extract of Ziziphus spina-christi. Method: The antioxidant property of ZnO-NPs was analyzed by the α, α-diphenyl-β-picrylhydrazyl (DPPH) and hydrogen peroxide (H₂O₂). Additionally, the diffusion agar method assessed the antimicrobial activities against bacteria and fungi. Results: ZnO-NPs synthesized by Z. spina-christi had shown promising H₂O₂ and DPPH free radical scavenging actions compared to vitamin C. The ZnO-NPs exhibited significant antibacterial activity against the tested bacteria with various susceptibility as a concentration-dependent effect. The largest zone of inhibition for Staphylococcus aureus (S. aureus) was observed (36 ± 2 mm) compared to Escherichia coli (E. coli) (15 ± 2 mm) by the same concentration of ZnO-NPs. The ZnO-NPs showed remarkable antifungal activity against Aspergillus niger. Conclusion: It can be concluded that, ZnO-NP have been imposed as suitable antimicrobial agent being able to combat both S. aureus and E. coli in vitro.

Excessive and continuous use of cosmetic products containing heavy metals can lead to harmful effects. International regulations mandate limited quantities of heavy metals contamination in cosmetic preparations to ensure consumer safety. This research aims to evaluate heavy metal and microbial contamination levels in selected cosmetic products available in the Palestinian market. We collected 35 samples randomly from 23 companies, representing four product types, and analyzed them for the presence of seven heavy metals: zinc (Zn), cadmium (Cd), lead (Pb), chromium (Cr), iron (Fe), copper (Cu), and arsenic (As) using an atomic absorption spectrometer. We also interviewed pharmacists who sold these cosmetics to assess their knowledge of allowed limits and toxic effects associated with increased heavy metal content in cosmetics. The results indicated that all tested products exceeded the allowed limit for Cd (9.5 ± 2.3 ppm), Cu (33.8 ± 9.2 ppm), and Zn (151.0 ± 7.4 ppm). However, none of the tested samples showed microbial contamination. These findings underscore the significant heavy metal contamination of cosmetics present in the Palestinian market. Thus, there is a pressing need to register and quality-test all cosmetic products sold in the Palestinian market and to raise the pharmacists' awareness and knowledge regarding heavy metals in cosmetics.

The rapidly increasing incidence of nonalcoholic fatty liver disease (NAFLD) is a growing health crisis worldwide. If not detected early, NAFLD progression can lead to irreversible pathological states, including liver fibrosis and cirrhosis. Using in vitro models to understand the molecular pathogenesis has been extremely beneficial; however, most studies have utilized only short-term exposures, highlighting a limitation in current research to model extended fat-induced liver injury. We treated Hep3B cells continuously with a low dose of oleic and palmitic free fatty acids (FFAs) for 7 or 28 days. Transcriptomic analysis identified dysregulated molecular pathways and differential expression of 984 and 917 genes after FFA treatment for 7 and 28 days respectively. DNA methylation analysis of altered DNA methylated regions (DMRs) found 7 DMRs in common. Pathway analysis of differentially expressed genes (DEGs) revealed transcriptomic changes primarily involved in lipid metabolism, small molecule biochemistry, and molecular transport. Western blot analysis revealed changes in PDK4 and CPT1A protein levels, indicative of mitochondrial stress. In line with this, there was mitochondrial morphological change demonstrating breakdown of the mitochondrial network. This in vitro model of human NAFL mimics results observed in human patients and may be used as a pre-clinical model for drug intervention.

The mode of action (MOA) underlying perfluorooctanoic acid (PFOA)-induced liver tumors in rats is proposed to involve peroxisome proliferator-activated receptor α (PPARα) agonism. Despite clear PPARα activation evidence in rodent livers, the mechanisms driving cell growth remain elusive. Herein, we used dose-responsive apical endpoints and transcriptomic data to examine the proposed MOA. Male Sprague-Dawley rats were treated with 0, 1, 5, and 15 mg/kg PFOA for 7, 14, and 28 days via oral gavage. We showed PFOA induced hepatomegaly along with hepatocellular hypertrophy in rats. PPARα was activated in a dose-dependent manner. Toxicogenomic analysis revealed six early biomarkers (Cyp4a1, Nr1d1, Acot1, Acot2, Ehhadh, and Vnn1) in response to PPARα activation. A transient rise in hepatocellular DNA synthesis was demonstrated while Ki-67 labeling index showed no change. Transcriptomic analysis indicated no significant enrichment in pathways related to DNA synthesis, apoptosis, or the cell cycle. Key cyclins including Ccnd1, Ccnb1, Ccna2, and Ccne2 were dose-dependently suppressed by PFOA. Oxidative stress and the nuclear factor-κB signaling pathway were unaffected. Overall, evidence for PFOA-induced hepatocellular proliferation was transient within the studied timeframe. Our findings underscore the importance of considering inter-species differences and chemical-specific effects when evaluating the carcinogenic risk of PFOA in humans.

Echinacea has grown in popularity due to its broad therapeutic benefits. Despite its popularity, comprehensive safety evaluations for three medicinal species are limited. In this study, female Sprague-Dawley rats received oral doses (0, 25, 50, 100, 200 mg/kg/d) of 75% (v/v) ethanol extract from the aerial parts of 9 Echinacea samples of three species - Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida - over a 7-day period. Blood and serum samples, collected twenty-four hours post the final dose, were analyzed for hematology and clinical chemistry parameters. The results revealed varied effects across the tested samples, with many parameters showing no discernible impacts at administered doses. Subtle alterations were observed in parameters such as relative liver weight, alkaline phosphatase (ALP), and platelet count. Parameters like relative spleen weight, alanine transaminase (ALT), glucose, urea, hematocrit, hemoglobin, and RBC count exhibited effects in only one out of the nine samples tested. These findings emphasize the heterogeneity in the effects of Echinacea. While the results suggest that Echinacea samples might be considered relatively safe, potential clinical implications warrant caution and underscore the importance of extended testing. A comprehensive toxicity profile assessment remains paramount to conclusively ascertain the safety of three Echinacea species.

Hexavalent chromium (Cr(VI)) is a well-known occupational and environmental human carcinogen. The cellular effect of Cr(VI) is complex and often nonspecific due to its ability to modulate multiple cellular targets. The toxicity of Cr(VI) is strongly linked to the generation of reactive oxygen species (ROS) during its reduction process. ROS can cause oxidation of cellular macromolecules, such as proteins, lipids, and DNA, thereby altering their functions. A major genotoxic effect of Cr(VI) that contributes to carcinogenesis is the formation of DNA adducts, which can lead to DNA damage. Modulations of cellular signaling pathways and epigenetics may also contribute to the carcinogenic effects of Cr(VI). Cr(VI) has a major impact on many aspects of mitochondrial biology, including oxidative phosphorylation, mitophagy, and mitochondrial biogenesis. These effects have the potential to alter the trajectory of Cr(VI)-induced carcinogenic process. This perspective article summarizes current understandings of the effect of Cr(VI) on mitochondria and discusses the future directions of research in this area, particularly with regard to carcinogenesis.

Methotrexate (MTX), a cytotoxic chemotherapeutic and immunosuppressant agent, is widely used in the treatment of autoimmune diseases and different types of cancers. However, its use has been limited by its life-threatening side effects, including nephrotoxicity and hepatotoxicity. The purpose of this study was to investigate the protective effect of sitagliptin on methotrexate (MTX)-induced nephrotoxicity in rats. Twenty-four rats were divided into four groups: control group, which received the vehicle for 6 days; MTX group, which received a single dose of MTX, followed by five daily doses of vehicle dosing; MTX + sitagliptin group, which received a single dose of MTX 1 h after the first sitagliptin treatment and six daily doses of sitagliptin; and sitagliptin group, which received sitagliptin for 6 days. Both MTX and sitagliptin were given as intraperitoneal injections at a dose of 20 mg/kg body weight. All rats were euthanized on the seventh day of the study. Kidney tissues were harvested and blood samples were collected. Serum levels of blood urea nitrogen (BUN) and creatinine were evaluated. Furthermore, catalase, glutathione peroxidase, superoxide dismutase activities, and malondialdehyde (MDA) levels were determined in kidney tissue. In addition, histopathological analysis was conducted. Histopathological evaluation showed that MTX-induced marked kidney injury. Biochemical analysis revealed a significant increase of BUN and creatinine in the serum of the MTX group. Furthermore, oxidative stress and depressed antioxidant system of the kidney tissues were evident in the MTX group. Sitagliptin did not affect these endpoints when administered alone, but it significantly attenuated the observed MTX-induced effects. These results suggest that sitagliptin exhibits potent anti-oxidant properties against the nephrotoxicity induced by MTX in rats.

The marine ecosystem around the Island of Newfoundland is contaminated by thyroid disrupting chemicals (TDCs). Coastal inhabitants may be exposed to TDCs through consumption of contaminated local seafood products and affecting thyroid functions. The aim of this study was to explore: (1) consumption frequency of local seafood products consumed by rural residents, (2) thyroid hormones (THs) and TDCs concentrations in residents, (3) relationships between local seafood consumption, TDC concentrations, and THs. Participants (n = 80) were recruited from two rural Newfoundland communities. Seafood consumption was measured through a validated seafood consumption questionnaire. Blood samples were collected from all participants and tested for THs (thyroid stimulating hormone, free thyroxine, free triiodothyronine) and TDCs, including polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), and dichlorodiphenyldichloroethylene (p,p'-DDE). Cod was the most frequently consumed local species, but there was a wide range of other local species consumed. Older participants (>50 years) had greater plasma concentrations of PBB-153, PCBs and p,p'-DDE, and males had higher concentrations of all TDCs than females. The consumption frequency of local cod was found to be positively associated with several PCB congeners, p,p'-DDE and ∑₁₄TDCs. There was no significant relationship between TDCs and THs in either simple or multivariate linear regression analyses.

Crocidolite is a carcinogen contributing to the pathogenesis of malignant mesothelioma. This study aimed to characterize the possible telomere-related events mediating the malignant transformation of mesothelial cells with and without SETD2 under crocidolite exposure. The crocidolite concentration resulting in 90% viable SETD2 knockout Met-5A (Met-5A^SETD2-KO) and Met-5A were estimated to be 0.71 μg/cm² and 1.8 μg/cm², respectively, during 72 h of exposure, which was further employed in chronical crocidolite exposure during a 72 h exposure interval per time up to 1 month. Chronical crocidolite-exposed Met-5A^SETD2-KO (chronical Cro-Met-5A^SETD2-KO) had higher colony formation and increased telomerase reverse transcriptase (TERT) protein levels than chronical crocidolite-exposed Met-5A (chronical Cro-Met-5A) and Met-5A^SETD2-KO. Chronical Cro-Met-5A^SETD2-KO had longer telomere length (TL) than chronical Cro-Met-5A, although there were no changes in TL for either chronical Cro-Met-5A or chronical Cro-Met-5A^SETD2-KO compared with their corresponding cells without crocidolite exposure. BIBR 1532, an inhibitor targeting TERT, partially reduced colony formation and TL for chronical Cro-Met-5A^SETD2-KO, while BIBR 1532 reduced TL but had no effect on colony formation for chronical Cro-Met-5A. Therefore, SETD2 deficient mesothelial cells are susceptible to malignant transformation during chronical crocidolite exposure, and TERT-dependent TL modification likely partially drives SETD2 loss-mediated early onset of mesothelial malignant transformation.

Elevated radon concentrations in drinking water pose an increased risk of cancer among nonsmokers. A Monte-Carlo Simulation was employed to assess the effective dose and cancer risk associated with radon exposure in humans, utilizing a systematic review and meta-analysis of related studies. These studies were sourced from databases including PubMed, Web of Science, Scopus, Science Direct, and Google Scholar, focusing on drinking water from Nigeria's six geopolitical zones. The random effects models revealed a ²²²Rn concentration in drinking water of Nigeria at 25.01, with 95% confidence intervals (CI) of 7.62 and 82.09, indicating significant heterogeneity of (I² = 100%; p < 0.001). The probabilistic risk of effective dose revealed a best-scenario (P 5%) at Kundiga and Magiro that exceeded the World Health Organization's (WHO) recommended effective dose limit of 200 µSv/y. Conversely, the worst-case scenario (P 95%) indicated concentrations surpassing the recommended limit at Kundiga, Edbe, Magiro, Ekiti, and Abeokuta. Excess Life Cancer Risk for infants, children, and adults attributed to the ingestion and inhalation of radon from various drinking water sources exceeded the recommended values of 0.2 x 10^-3 established by the International Commission on Radiological Protection (ICRP) and the United Nations Scientific Committee on the Effect of Atomic Radiation (UNSCEAR). It underscores the necessity for treating radon-polluted water, employing methos such as aeration and granular activated carbon (GAC) processes.