Toxicology and Industrial Health最新文献

Smoking or occupational exposure leads to low concentrations of acrolein on the surface of the airways. Acrolein is involved in the pathophysiological processes of various respiratory diseases. Reports showed that acrolein induced an increase in mitochondrial reactive oxygen species (mROS). Furthermore, exogenous H₂O₂ was found to increase intracellular Zn²⁺ concentration ([Zn²⁺]ᵢ). However, the specific impact of acrolein on changes in intracellular Zn²⁺ levels has not been fully investigated. Therefore, this study aimed to investigate the effects of acrolein on mROS and [Zn²⁺]ᵢ in A549 cells. We used Mito Tracker Red CM-H₂Xros (MitoROS) and Fluozin-3 fluorescent probes to observe changes in mROS and intracellular Zn²⁺. The results revealed that acrolein increased [Zn²⁺]ᵢ in a time- and dose-dependent manner. Additionally, the production of mROS was observed in response to acrolein treatment. Subsequent experiments showed that the intracellular Zn²⁺ chelator TPEN could inhibit the acrolein-induced elevation of [Zn²⁺]ᵢ but did not affect the acrolein-induced mROS production. Conversely, the acrolein-induced elevation of mROS and [Zn²⁺]ᵢ were significantly decreased by the inhibitors of ROS formation (NaHSO₃, NAC). Furthermore, external oxygen free radicals increased both [Zn²⁺]ᵢ levels and mROS production. These results demonstrated that acrolein-induced elevation of [Zn²⁺]ᵢ in A549 cells was mediated by mROS generation, rather than through a pathway where [Zn²⁺]ᵢ elevation leads to mROS production.

Copper oxide nanomaterials (CuO NPs) have been widely utilized in many fields, including antibacterial materials, anti-tumor, osteoporosis treatments, imaging, drug delivery, cosmetics, lubricants for metallic coating, the food industry, and electronics. Little is known about the potential risk to human health and ecosystems. The present work was conducted to investigate the ultrastructural changes induced by 20 ± 5 nm CuO NPs in hepatic tissues. Adult healthy male Wister albino rats were exposed to 36 intraperitoneal (ip) injections of 25 nm CuO NPs (2 mg/kg bw). Liver biopsies from all rats under study were processed for transmission electron microscopy (TEM) processing and examination for hepatic ultrastructural alterations. The hepatic tissue of rats exposed to repeated administrations of CuO NPs exhibited the following ultrastructural alterations: extensive mitochondrial damage in the form of swelling, crystolysis and matrix lysis, formation of phagocytized bodies and myelin multilayer figures, lysosomal hyperplasia, cytoplasmic degeneration and vacuolation, fat globules precipitation, chromatin clumping, and nuclear envelope irregularity. The findings indicated that CuO NPs interact with the hepatic tissue components and could induce alterations in the hepatocytes with the mitochondria as the main target organelles of copper nanomaterials. More work is recommended for better understanding the pathogenesis of CuO NPs.

Good mechanical properties and low costs have led to a global expansion of plastic production and use. Unfortunately, much of this material can be released into the environment as a waste product and cleaved into micro- and nanoplastics (NPs) whose impact on the environment and human health is still largely unknown. Considering the growing worldwide awareness on exposure to chemicals that can act as endocrine disruptors, a systematic review was performed to assess the impact of NPs on the endocrine function of in vitro and in vivo models. Although a limited number of investigations is currently available, retrieved findings showed that NPs may induce changes in endocrine system functionality, with evident alterations in reproductive and thyroid hormones and gene expression patterns, also with a trans-generational impact. Nanoplastic size, concentration, and the co-exposure to other endocrine disrupting pollutants may have an influencing role on these effects. Overall, although it is still too early to draw conclusions regarding the human health risks derived from NPs, these preliminary results support the need for further studies employing a wider range of plastic polymer types, concentrations, and time points as well as species and life stages to address a great variety of endocrine outcomes and to achieve a broader and shared consensus on the role of NPs as endocrine disruptors.

Manganese (Mn) is an abundant element used for commercial purposes and is essential for the proper function of biological systems. Chronic exposure to high Mn concentrations causes Manganism, a Parkinson's-like neurological disorder. The pathophysiological mechanism of Manganism remains unknown; however, it involves mitochondrial dysfunction and oxidative stress. This study assessed the neuroprotective effect of probucol, a hypolipidemic agent with anti-inflammatory and antioxidant properties, on cell viability and oxidative stress in slices of the cerebral cortex and striatum from adult male Wistar rats. Brain structure slices were kept separately and incubated with manganese chloride (MnCl₂) and probucol to evaluate the cell viability and oxidative parameters. Probucol prevented Mn toxicity in the cerebral cortex and striatum, as evidenced by the preservation of cell viability observed with probucol (10 and 30 μM) pre-treatment, as well as the prevention of mitochondrial complex I inhibition in the striatum (30 μM). These findings support the protective antioxidant action of probucol, attributed to its ability to prevent cell death and mitigate Mn-induced mitochondrial dysfunction.

Textile effluents, although their composition can vary considerably, typically contain high levels of dissolved salts and exhibit wide variations in pH. Ecotoxicological studies regarding the effects of these parameters, however, have been limited owing to the need for sensitive and easy-to-handle bioindicators that require low amounts of sampling, are cost-effective, time-efficient, and ethically endorsed. This kind of study, additionally, demands robust multi-factorial statistical designs that can accurately characterize the individual and combined relationship between variables. In this research, Response Surface Methodology (RSM) was used to calculate the individual and interaction effects of NaCl concentration and pH value of a Simulated Textile Effluent (STE) on the development rate (DR) of the bioindicators: Bacillus subtilis bacteria and Lactuca sativa lettuce. The results demonstrated that the bioindicators were sensitive to both NaCl and pH factors, where the relative sensitivity relationship was B. subtilis > L. sativa. The quadratic equations generated in the experiments indicated that increased concentrations of 50-250 mg L^-1 of NaCl caused a perturbance of 1.40%-34.40% on the DR of B. subtilis and 0.50%-12.30% on L. sativa. The pH factor at values of 3-11 caused an alteration of 27.00%-64.78% on the DR of the B. subtilis and 51.37%-37.37% on the L. sativa. These findings suggest that the selected bioindicators could serve as effective tools to assess the ecotoxicological effects of textile effluents on different ecological systems, and the RSM was an excellent tool to consider the ecotoxicological effects of the parameters and to describe the behavior of the results. In conclusion, the NaCl and pH factors may be responsible for disrupting different ecosystems, causing imbalances in their biodiversity and biomass. Before discharge or reuse, it is suggested to remove salts and neutralize pH from textile effluents and, mostly, develop novel, eco-friendlier textile processing techniques.

Phthalate compounds were found to disrupt the endocrine system and alter transcriptomes during human embryonic development. In our previous work, we have isolated and reported two such phthalates di-(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) from Brevibacterium mcbrellneri bacteria and evaluated their bioactive properties. Naturally derived phthalates might be less toxic compared with synthesized molecules. We have investigated biologically isolated phthalates to understand the possible genotoxic effects in mice and further investigated in silico binding and polymerization of β-tubulin. Three sub-lethal concentrations of DEHP (150 μM, 175 μM, and 200 μM) and DBP (10 μM, 15 μM, and 30 μM) were studied. The results showed that the phthalates were found to be highly genotoxic in nature. However, the pattern of genotoxic effects was not found to be dose-dependent in the induction of chromosome aberrations (CA), micronuclei (MN), and changes in the mitotic index (MI) in cells. In silico studies of phthalates on polymerization of β-tubulin suggested that both DBP and DEHP were able to interact with the hydrogen bonds and make strong van der Waals interactions with β-tubulin thereby possibly causing destabilization of microtubule network. Our study suggests that these phthalates might be playing an important role in normal cell division thereby showing highly genotoxic effects.

Methomyl is a carbamate insecticide with confirmed testicular toxicity. This study intended to observe the effect of methomyl on testicular cells and the protective effect of folic acid through in vitro experiments. The GC-1 spermatogonia, TM4 Sertoli cells, and TM3 Leydig cells were treated with methomyl (0, 250, 500, and 1000 μM) with or without folic acid (0, 10, 100, and 1000 nM) for 24 h. It was found that methomyl increased cytotoxicity to testicular cells in a dose-dependent manner. In spermatogonia, methomyl significantly inhibited the expression of proliferation genes Ki67 and PCNA at 1000 μM, and increased the expression of apoptosis genes Caspase3 and Bax at each dose. In Sertoli cells, methomyl dose-dependently inhibited the expression of blood-testis barrier function genes TJP1, Cx43, and N-cadherin, but did not affect Occludin and E-cadherin. In Leydig cells, methomyl inhibited the expression of steroid synthase P450scc, StAR, Hsd3b1 and down-regulated the level of testosterone, but did not affect Cyp17a1 and Hsd17b1. Further, folic acid could basically reduce the damage caused by methomyl. This study provided new insights into the toxicity of methomyl and the protective effect of folic acid.

Trichloroethylene (TCE) is a metal detergent commonly used in industry that can enter the human body through the respiratory tract and skin, causing occupational medicamentosa-like dermatitis due to TCE (OMDT) and multiple organ damage, including liver failure. However, the pathogenesis of liver injury remains unclear. Kupffer cells (KCs) are important tissue macrophages in the body because the polarization of KCs plays a crucial role in immune-mediated liver injury. However, the mechanism of KCs polarization in TCE-induced immune liver injury has not been thoroughly elucidated. In this study, we investigated the effect of TCE-induced KCs polarization on liver function and signal transduction pathways using the TCE sensitization model developed by our group. BALB/c mouse skin was exposed to TCE for sensitization, and an increase in the expression of M1 macrophage-specific markers (CD16/CD32, iNOS), M1 macrophage-specific cytokines IL-1β, and IFN-γ, P-JAK-1 and P-STAT1 levels were also found to be dramatically increased. When using low doses of gadolinium trichloride (GdCl₃), the expression of these proteins and mRNA was significantly reduced. This phenomenon indicates that GdCl₃ blocks TCE-induced polarization of KCs and suggests that the IFN-γ/STAT1 signaling pathway may be involved in the polarization process of KCs. These findings clarify the relationship between the polarization of KCs and immune liver injury and highlight the importance of further study of immune-mediated liver injury in TCE-sensitized mice.

Man-made vitreous fibers (MMVF) are a class of inorganic fibrous materials that include glass and mineral wools, continuous glass filaments, and refractory ceramic fibers valued for their insulative properties in high temperature applications. Potential health effects from occupational exposure to MMVF have been investigated since the 1970s, with focus on incidence of respiratory tract cancer among MMVF-exposed production workers. The general population may experience exposure to MMVF in residential and/or commercial buildings due to deterioration, construction, or other disruption of materials containing these fibers. Numerous studies have characterized potential exposures that may occur during material disruption or installation; however, fewer have aimed to measure background MMVF concentrations in residential and commercial spaces (i.e., non-production settings) to which the general population may be exposed. In this study, we reviewed and synthesized peer-reviewed studies that evaluated respirable MMVF exposure levels in non-production, indoor environments. Among studies that analyzed airborne respirable MMVF concentrations, 110-fold and 1.5-fold differences in estimated concentrations were observed for those studies utilizing phase contrast optical microscopy (PCOM) versus transmission electron microscopy (TEM) and scanning electron microscopy (SEM), respectively. A positive correlation was observed between respirable air concentrations of MMVF and total surface concentrations of MMVF in seldom-cleaned areas. Ultimately, available evidence suggests that both ambient air and surface concentrations of MMVF in indoor environments are consistently lower than exposure limits developed to prevent negative health outcomes among sensitive populations.

To meet the strict requirements of reducing sulfur emissions, an increasing number of commercial ships have installed exhaust gas cleaning systems (EGCSs). However, wash water produced during the cleaning process is discharged back to the marine environment. We investigated the effects of closed-loop scrubber (natrium-alkali method) wash water on three trophic species. Severe toxic effects were found when Dunaliella salina, Mysidopsis bahia, and Mugilogobius chulae were exposed to 0.63-6.25, 0.63-10, and 1.25-20% concentrations of wash water, respectively. The 50% effective concentration in 96 h (EC₅₀-96 h) for D. salina was 2.48%, and the corresponding total polycyclic aromatic hydrocarbons (PAHs) and heavy metals were 22.81 and 23.67 μg L^-1. The 50% lethal concentration in 7 d (LC₅₀-7 d) values for M. bahia and M. chulae were 3.57% and 20.50%, respectively. The lowest observed effect concentration (LOEC) values for M. bahia and M. chulae were 1.25% and 2.5%, respectively, and the corresponding total PAHs and heavy metals were 11.50 and 11.93 and 22.99 and 23.86 μg L^-1. M. bahia's body weight was negatively correlated with the amount of wash water. Low concentrations of wash water (0-5%) had no significant effect on the reproduction of M. bahia. Although concentrations of 16 PAHs and 8 heavy metals are known, different compounds might react with each other and form more unknown toxic substances, and the measured toxicity comes from synergistic effects between various pollutants. Therefore, future work is needed to clarify other more toxic contaminants in wash water. We highly recommend that wash water be treated before being discharged to the marine environment.