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

Objective: This study aims to explore the mechanism of miR-30d-5p in regulating the development of lung squamous cell carcinoma (LUSC) via targeting DBF4.

Methods: Bioinformatics methods were employed to analyze the differentially expressed genes in LUSC tissue microarray. qRT-PCR was employed to detect the expression of miR-30d-5p and DBF4 mRNA in normal human bronchial epithelial cells and LUSC cells. CCK-8 was used to detect LUSC cell activity. Wound healing assay was employed to detect the migratory ability of LUSC cells. Transwell was employed to detect invasive ability. Dual-luciferase reporter assay was used to detect the targeting relationship between miR-30d-5p and DBF4. Western blot was used to detect the protein expression of marker molecules associated with epithelial-mesenchymal transition (EMT).

Results: In this study, the expression of miR-30d-5p in LUSC cell lines was found to be obviously low compared with that in normal human bronchial epithelial cell line, which was opposite to the expression of DBF4. Dual-luciferase reporter assay verified that miR-30d-5p could target DBF4 and the overexpression of miR-30d-5p downregulated the expression of DBF4. Overexpression of DBF4 promoted the proliferation, migration, invasion, and EMT of LUSC, whereas over-expression of miR-30d-5p could weaken the promotion of DBF4 on cancer cells.

Conclusion: miR-30d-5p downregulates the expression of DBF4 to regulate the development of LUSC.

Chronic kidney disease of unknown etiology (CKDu) is a major health issue in agricultural areas in Sri Lanka. Despite many attempts to identifying causative factors of CKDu, the real cause/s remain/s elusive to date. Understanding the progression of potential etiologies may provide valuable insight into this quest. Literature relevant to CKDu addresses several etiologies, including quality of drinking water in the affected areas including hardness, fluoride, ionicity, agrochemical and heavy metal contaminations, consumption of contaminated food, and the genetic makeup of vulnerable populations. Progression of the etiologies revealed persistent interest in heavy metals of multiple origins: waterborne, foodborne, or soilborne. Secondary factors, such as water hardness, fluoride, and ionicity appear to act synergistically, aggravating the role of heavy metals on the onset, and the progression of CKDu. Demographical factors, such as male sex, over 50 years of age, agriculture-related occupation, and the consumption of contaminated water and food are intricately related with the disease progression while other minor risk factors such as smoking, alcohol consumption, etc. exasperate the disease condition. Since, none of these etiologies are examined adequately, conducting laboratory exposure studies under in-vivo and in-vitro settings to understand their role in CKDu is crucial.

Nigeria receives copious annual precipitation to nourish its forests and agriculture, it has an extensive river drainage system, and it possesses valuable mineral deposits that stimulate both commercial and artisan mining activities. The combination of these features complicates Nigeria's efforts to produce adequate amounts of healthy foods to support its population. Toxic heavy metals like lead, cadmium, and mercury, and toxic metalloids such as arsenic, are also present in its mineral deposits and they migrate gradually into the soil and water of Nigeria by natural means. However, mining activities can liberate higher levels of toxic metals, which adversely affect Nigerian ecosystems and its food chains. Thus, environmental pollution due to anthropogenic activities is a major public health concern in Nigeria. This review covers the importance of native Nigerian and African wild and cultivated plants along with livestock and wild animals as sentinel species to evaluate heavy metals as environmental stressors and the use of sentinel species for food safety monitoring and for predicting potential risks to human health.

Pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic phytochemicals. Upon metabolic activation, PAs produce dehydropyrrolizidine alkaloids (dehydro-PAs) as reactive primary pyrrolic metabolites. Dehydro-PAs are unstable, facilely hydrolyzed to (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP). Both dehydro-PAs and DHP are capable of binding to cellular DNA and proteins to form DHP-DNA and DHP-protein adducts leading to tumorigenicity and cytotoxicity. We recently determined that the reaction of dehydro-PAs with glutathione and cysteine generated 7-glutathione-DHP (7-GS-DHP) and 7-cysteine-DHP, respectively which can also bind to DNA to produce DHP-DNA adducts. In this study, we determined the effects of glutathione and cysteine on the induction of hepatocytotoxicity and the formation of DHP-DNA adducts in primary hepatocytes cultured with riddelliine and monocrotaline. We found that both glutathione and cysteine can drastically reduce hepatotoxicity while the levels of DHP-DNA adduct formation are slightly affected.

Arsenic contamination in the groundwater of Southern Assam, India is well-documented. A specific type of smokeless tobacco (sadagura, SG) is highly prevalent among the local population. Thus, the present study is aimed to evaluate the toxicological implications of arsenic and smokeless tobacco co-exposure on the reproductive health of female mice. The estrous cycle of experimental animals was monitored for 30 days. Histopathological studies and comet assay of ovarian and uterine tissues were performed after 30 days of exposure to SG and arsenic (sodium arsenite, SA). Oxidative stress was estimated biochemically by taking tissue glutathione, lipid peroxidation (LPO), and superoxide dismutase activity as endpoints. Our findings indicated a prolonged diestrus phase in the SG + L + SA group (p < 0.001). Histopathological study revealed abnormal tissue architecture in treated groups. Comet assay study showed that SG + SA exposure significantly induced DNA damage in test animals. The elevated LPO level in the SG + SA group indicated oxidative stress generation in the reproductive tissues. The present study suggests that female reproductive organs are vulnerable to SA and SG and oxidative stress generation may be the possible mechanism behind DNA damage, impaired follicular growth, atresia, and altered estrous cycle in the mice test system.

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.

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.

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.

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.