Environmental Toxicology最新文献

Subways are widely used in major cities around the world, and subway fine particulate matter (PM_2.5) is the main source of daily PM_2.5 exposure for urban residents. Exposure to subway PM_2.5 leads to acute inflammatory damage in humans, which has been confirmed in mouse in vivo studies. However, the concrete mechanism by which subway PM_2.5 causes airway damage remains obscure. In this study, we found that subway PM_2.5 triggered release of pro-inflammatory cytokines such as interleukin 17E, tumor necrosis factor α, transforming growth factor β, and thymic stromal lymphopoietin from human bronchial epithelial cells (BEAS-2B) in a dose–effect relationship. Subsequently, supernatant recovered from the subway PM_2.5 group significantly increased expression of the aforementioned cytokines in BEAS-2B cells compared with the subway PM_2.5 group. Additionally, tight junctions (TJs) of BEAS-2B cells including zonula occludens-1, E-cadherin, and occludin were decreased by subway PM_2.5 in a dose-dependent manner. Moreover, supernatant recovered from the subway PM_2.5 group markedly decreased the expression of these TJs compared with the control group. Furthermore, inhibitors of toll-like receptors (TLRs) and nuclear factor-kappa B (NF-κB), as well as chelate resins (e.g., chelex) and deferoxamine, remarkably ameliorated the observed changes of cytokines and TJs caused by subway PM_2.5 in BEAS-2B cells. Therefore, these results suggest that subway PM_2.5 induced a decline of TJs after an initial ascent of cytokine expression, and subway PM_2.5 altered expression of both cytokines and TJs by activating TLRs/NF-κB-dependent pathway in BEAS-2B cells. The metal components of subway PM_2.5 may contribute to the airway epithelial injury.

Paraquat (PQ) is a noxious herbicide which adversely affects the vital organs including male reproductive system. Sudachitin (SCN) is a naturally occurring flavonoid that demonstrates a wide range of biological potentials. The current study was designed to investigate the alleviative potential of SCN to avert PQ-induced testicular toxicity in rats. Forty-eight male rats (Rattus norvegicus) were apportioned into four groups including control, PQ (5 mg/kg), PQ + SCN (5 mg/kg + 30 mg/kg), and SCN (30 mg/kg) only treated group. Our findings elucidated that PQ treatment reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and its antioxidant genes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR) and glutathione peroxidase (GPx), while elevating the levels of reactive oxygen species (ROS), and malondialdehyde (MDA). Furthermore, PQ intoxication upregulated the expressions of Keap-1 while downregulating the expression of 3-beta hydroxysteroid dehydrogenase (3β-HSD), 17-beta hydroxysteroid dehydrogenase (17β-HSD), and steroidogenic acute regulatory protein (StAR). Moreover, sperm anomalies were increased following the exposure to PQ. Besides, PQ exposure decreased the levels of plasma testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) while increasing the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), interleukin-1beta (IL-1β), and cyclooxygenase-2 (COX-2). Additionally, PQ treatment escalated the expressions of cysteinyl aspartate-specific proteases-3 (Caspase-3) and Bcl-2-associated X-protein (Bax) while downregulating the expressions of B-cell lymphoma-2 (Bcl-2). Furthermore, PQ exposure disrupted the normal architecture of testicular tissues. However, SCN treatment remarkably protected the testicular tissues via regulating the aforementioned disruptions owing to its antioxidant, anti-inflammatory, and androgenic potential.

Phenethyl isothiocyanate (PEITC), a natural product, exists in biological activities, including anticancer activity in many human cancer cells. No information shows that PEITC affects DNA damage in human retinoblastoma (RB) cells in vitro. In this study, the aim of experiments was to determine whether PEITC decreased total viable cell number or not by inducing protein expressions involved in DNA damage and repair in Y79 RB cells in vitro. Total cell viability was measured by PI exclusion assay, and PEITC reduced the total Y79 viable cell numbers in a dose-dependent manner. DNA condensation and DNA impairment were conducted by DAPI staining and comet assays, respectively, in Y79 cells. The findings show that PEITC induced DNA condensation dose-dependently based on the brighter fluorescence of cell nuclei stained by DAPI staining. PEITC-induced DNA damage showed a more extended DNA migration smears than that of the control, which was performed by a comet assay. Western blotting was performed to measure the protein expressions involved in DNA damage and repair, which showed that PEITC at 2.5–10 μM increased NRF2, HO-1, SOD (Mn), and catalase; however, it decreased SOD (Cu/Zn) except 10 μM PEITC treatment, and decreased glutathione, which were associated with oxidative stress. Furthermore, PEITC increased DNA-PK, MDC1, H₂A.X^pSer139, ATM^pSer1981, p53, p53^pSer15, PARP, HSP70, and HSP90, but decreased TOPIIα, TOPIIβ, and MDM2^pSer166 that were associated with DNA damage and repair mechanism in Y79 cells. The examination from confocal laser microscopy shows that PEITC increased H₂A.X^pSer139 and p53^pSer15, and decreased glutathione and TOPIIα in Y79 cells. In conclusion, the cytotoxic effects of PEITC on reducing the number of viable cells may be due to the induction of DNA damage and the alteration of DNA repair proteins in Y79 cells in vitro.

Oxyresveratrol (OxyR) exerts biological and pharmacological effects in a variety of tumor cells, including antioxidant action, antitumor activity, and proapoptotic effects. However, the regulation of targeted signaling pathways by OxyR and the mechanism underlying these effects in human renal cell carcinoma (RCC) have been less studied. We observed that OxyR at noncytotoxic doses did not affect the growth of human RCC cells or normal kidney HK2 cells. OxyR inhibited ACHN and Caki-1 cell migration and invasion through targeting matrix metalloproteinase 1 (MMP1) expression. Analysis of clinical databases showed that high MMP1 expression is associated with lower overall survival (OS) in these cancers (p < 0.01). OxyR significantly inhibited the mRNA and protein expression of Sp1. Furthermore, luciferase assay results showed that OxyR inhibited Sp1 transcriptional activity. Additionally, OxyR preferentially suppressed the activation of ERK and PKCα. Treatment with U0126 (MEK inhibitor) or G06976 (PKCα inhibitor) clearly decreased Sp1 and MMP1 expression and inhibited RCC cell migration and invasion. In conclusion, OxyR may be a potential antitumor therapy for the inhibition of migration and invasion by controlling p-ERK/Sp1 and p-PKCα/Sp1-mediated MMP1 expression in RCC.