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

Pyrrolizidine alkaloids (PAs) are extensively distributed in plants and are known to damage hepatic sinusoidal endothelial cells (HSECs) via metabolic activation mediated by hepatic cytochrome P450 enzymes (CYPs), particularly the CYP3A4 isozyme. Different PAs have distinct toxic potencies and their toxic effects on HSECs are difficult to be determined in cultured cells, because HSECs lack the key CYP3A4 isozyme for metabolic activation. This study aims to establish a novel, convenient and reliable CYP3A4-expressing HSEC model using human HSECs transduced with lentivirus carrying CYP3A4-ires-eGFP, for evaluating the hepatotoxicity of different PAs on their target HSECs. The developed CYP3A4-expressing HSEC (HSEC-CYP3A4) model was verified by the expression of GFP and CYP3A4 and by the ability to metabolize nifedipine, a classic CYP3A4 substrate. Treated with retrorsine, a representative toxic PA, HSEC-CYP3A4 cells showed significantly reduced cell viability, depletion of GSH, and increased formation of pyrrole-protein adducts. Furthermore, this newly developed cell model successfully discriminated the cytotoxic potency of different PAs evidenced by their IC₄₀ values. In conclusion, the established HSEC-CYP3A4 cell model can be used as a rapid screening platform for assessing the relative potencies of individual PAs on their target HSECs and for investigating the mechanisms underlying PA-induced hepatic sinusoidal damage.

Triclosan (TCS), a well-studied antimicrobial compound and an environmental pollutant, is present in many household products. A systematic survey of TCS-antibiotic-bacteria interactions is lacking. We wish to understand the origin of such interactions by testing 16 phylogenetically well-characterized bacteria for their sensitivities to 6 different classes of antibiotics with or without the presence of TCS. Our results show that TCS interacts synergistically with some antibiotics against some Bacilli species. TCS could also interact antagonistically with other antibiotics against certain bacteria, including pathogens such as Pseudomonas aeruginosa and Stenotrophomonas maltophilia. Antagonism between drugs often coincided with the concomitant enhanced removal of Ethidium bromide (EtBr) from the cells. Enterococcus faecalis shows a unique response to TCS. High levels of TCS inhibits E. faecalis. Cells survive at lower TCS concentrations, and these cells can remove EtBr more readily than unexposed cells. At even lower TCS concentration, cell-growth is inhibited again, causing the culture to exhibit a unique extra inhibition zone around the TCS-disk. The TCS-antibiotic-bacteria interaction profiles of some bacteria do not follow their bacterial phylogenetic relations. This suggests that such interactions may be related to horizontal gene transfer among different bacteria.

The combination of semiconductor and metal nanocomponents represents an effective way for design of photocatalysts with high efficiency. It is expected that this strategy can be applied to design photo-regulated nanozymes. To prove this concept, BiOBr/PtRu hybrid nanostructures have been fabricated by depositing PtRu nanoparticles on BiOBr nanosheets through a templating co-reduction method. The formation of BiOBr/PtRu hybrid nanostructures was confirmed by TEM, XRD and XPS. BiOBr/PtRu hybrid nanostructures exhibited excellent enzyme-like activities (peroxidase, oxidase, ferroxidase) as well as the ability to scavenge DPPH free radicals. When exposed to light irradiation (λ > 420 nm), it was found that BiOBr/PtRu hybrid nanostructures not only exhibit improved photocatalytic degradation, but also exhibit enhanced peroxidase- and oxidase-like activity. Due to the photocatalytic effect and the higher charge separation and utilization efficiency caused by heterojunctions, a light-enhanced enzyme-like activity mechanism was proposed. These results will be of value to design high efficiency nanozymes using light for biological and environmental applications.

The hepatotoxic pyrrolizidine alkaloids (PAs) are metabolically activated in the liver to form reactive dehydro-PAs, which generate pyrrole-protein adducts leading to hepatotoxicity. Monocrotaline, but not other PAs, is also pneumotoxic, supposedly due to the migration of the liver-generated corresponding dehydro-PA into the lung to form pyrrole-protein adducts to induce pneumotoxicity. The present study investigated whether other PAs are also pneumotoxic. Metabolic activation of four representative hepatotoxic PAs, monocrotaline, retrorsine, riddelliine and clivorine, was investigated using rat liver or lung S9 incubation. All PAs produced pyrrole-protein adducts significantly in rat liver S9 but negligible in lung S9 fraction, revealing that liver is the key organ responsible for metabolic activation generating dehydro-PAs. Furthermore, these four PAs and another two PAs present in the alkaloid extract of Gynura segetum, a widely used PA-producing herb responsible for human PA poisonings in China, were orally administered to rats using the same hepatotoxic dose of 0.2 mmol/kg. All six PAs induced pneumotoxicity in rats within 48 h. The results demonstrated that pneumotoxicity could be a common phenomenon of PAs and the liver-derived dehydro-PAs might move to the lung and form pyrrole-protein adducts, leading to pulmonary toxicity.

The large-scale applications of Triclosan in industrial and household products have created many health and environmental concerns. Despite the fears of its drug-resistance and other issues, Triclosan is still an effective drug against many infectious organisms. Knowing the cross-interactions of Triclosan with different antibiotics, bacteria, and humans can provide much-needed information for the risk assessment of this drug. We review the current understanding of the antimicrobial mechanisms of Triclosan, how microbes become resistant to Triclosan, and the synergistic and antagonistic effects of Triclosan with different antibiotics. Current literature on the clinical applications of Triclosan and its effect on fetus/child development are also summarized.

Lead (Pb) is ubiquitous in our environment and causes many pathophysiological health effects, including dental diseases. Dental Pb levels are considered good biological indicators of environmental and occupational Pb exposure. Pb in blood and saliva causes imbalances in the growth of oral microflora. The pH of saliva decreases, interferes with and interacts with bone-seeking elements, changes oral inflammatory parameters, generates reactive oxygen species, causes oxidative damage, and delays the mineralization process, leading to dental diseases. Pb's dental diseases include periodontitis, enamel lesions and defects, fluorosis, Burton's line, and tooth loss. Environmental and physiological factors, including age, gender, tooth type and position, pregnancy and lactation, eating and drinking habits, smoking habits, and exposures from Pb-contaminated residential and occupational areas, affect the distribution of Pb in blood, bone, and saliva, which contributes to dental diseases. However, living and working in Pb free areas can prevent environmental and occupational Pb exposure. Healthy lifestyles and eating habits, prohibiting smoking and alcohol drinking, further help prevent Pb exposure. Also, the fluoridation of water, salt, and milk provide nutritional supplements of trace elements, which can help prevent teeth from absorbing Pb from the environment, thereby reducing the risk of dental diseases.

Microplastics (MPs) and associated contaminants have become a major environmental concern. From available literature, their ubiquitous presence is now well established. However, the kind and level of toxicological impacts these MPs accomplish on various life forms are not well understood. Nevertheless, the environmental toxicity of MP is now being revealed gradually with supporting studies involving groups of lower organisms. Additionally, the presence of microplastics also disturbs the functions of ecosystem through affecting the vulnerable life forms, thus ecological manifestations of MPs also need to be analyzed. The present review encompasses an overview of toxicological effects mediated by various types of MPs present in the environment; it covers the types of toxicity they may cause and other effects on humans and other species. In this review, aquatic systems are used as primary models to describe various eco-toxicological effects of MPs. Various research gaps as well as methods to alleviate the level of MPs, and future strategies are also comprehensively highlighted in the review.

Ascorbic acid is often used to enhance iron absorption in nutritional interventions, but it produces pro-oxidant effects in the presence of iron. This study aimed to evaluate ascorbate's role in iron toxicity on intestinal resistance against foodborne pathogens during iron supplementation/fortification. In polarized Caco-2 cell monolayers, compared to the iron-alone treatment, the iron-ascorbate co-treatment caused more than 2-fold increase in adhesion, invasion and translocation of Salmonella enterica serovar Typhimurium. According to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase release and transepithelial electrical resistance, the iron-ascorbate co-treatment resulted in reduced cell viability and increased impairment of cell membrane and paracellular permeability compared to the iron-alone treatment. Butylated hydroxytoluene protected cells against these prooxidant toxicities of ascorbate. Ascorbate completely restored iron-induced intracellular oxidant burst and depletion of cytosolic antioxidant reserve, according to dichlorodihydrofluorescein fluorescence and intracellular reduced glutathione levels. In Salmonella-infected C57BL/6 mice, iron-ascorbate co-supplementation resulted in greater loss of body weight and appetite, lower survival rate, shorter colon length, heavier intestinal microvilli damage, and more intestinal pathogen colonization and translocation than the iron-alone supplementation. Overall, ascorbate would exacerbate iron toxicity on intestinal resistance against Salmonella infection through pro-oxidant impairment of intestinal epithelial barrier from extracellular side and/or by facilitating intestinal pathogen colonization.

Environmental and occupational exposures to heavy metals have led to various deleterious damages to the biological system of which infertility is one of them. Infertility is a global public health concern, affecting 15% of all couples of reproductive age. Out of the 100% cases of reported infertility among couples, 40% of the cases are related to male factors; including decreased semen quality. This review focuses on the recent mechanistic perspectives of heavy metal-induced male reproductive toxicity. The associated toxic metal-mediated mechanisms of male reproductive toxicity include ion mimicry, disruption of cell signaling pathways, oxidative stress, altered gene expression, epigenetic regulation of gene expression, apoptosis, disruption of testis/blood barrier, inflammation and endocrine disruption. The current literature suggests that non-coding RNAs (ncRNAs) mediate paternal intergenerational epigenetic inheritance and thus has a direct functional importance, as well as possess novel biomarker potential, for male reproductive toxicity. To identify the specific ncRNAs with the most profound impacts on heavy metal-induced male reproductive toxicity should be thrust of further research.