Journal of Toxicology and Environmental Health-Part A-Current Issues最新文献

Alzheimer 's disease, a neurodegenerative disease, is considered a serious global type of dementia affecting predominantly elderly associated with progressive memory loss. Alzheimer 's disease exhibits typical pathological manifestations including neuronal loss, β-amyloid deposition, and tau protein neurofibrillary tangles. Significantly increased expression of long-non -coding transcript RNA, LncRNA SNHG1, was detected in the brain of AD patients. However, it is not clear whether knockdown of LncRNA SNHG1 might improve autophagy function in SH-SY5Y cells and reduce the number of apoptotic cells. The aim of this study was to (1) examine the role of LncRNA SNHG1 on autophagic function of SH-SY5Y cells following induction by Aβ1-42 and (2) elucidate the underlying mechanisms. SH-SY5Y cells were transfected with lentiviral vectors to construct a cell line with stable genetic ability to knock down LncRNA SNHG1 and compared to control empty vector cell line. Following induction with Aβ1-42 for 24 hr, an AD cell model was constructed. Downregulation with LncRNA SNHG1 significantly increased cell viability and lowered the number of apoptotic cells. Concomitantly downregulation of the expression of LncRNA SNHG1 in SH-SY5Y cells induced significant decrease in expression of p-tau and caspase3 associated with elevated expression of Beclin1 and AMBRA1. Our results showed that knockdown of LncRNA SNHG1 in SH-SY5Y cells reduced the number of apoptotic cells by enhancing expression of Beclin1 and AMBRA1. Data suggest that by knocking down the expression of LncRNA SNHG1 may be considered a potential target for compounds to treat AD.

Vochysia divergens (Vochysiaceae), present in the flooded fields of Pantanal in the state of Mato Grosso, Brazil, is traditionally used to treat infections. However, studies on the toxicological safety of using the stem bark of this vegetable are lacking. This study aimed to investigate acute oral toxicity using rats, genotoxicity utilizing mice, and toxicity to non-vertebrate animals, the insect Galleria mellonella and the nematode Caenorhabditis elegans following exposure to V. divergens stem bark ethanolic extract (VDSE). In addition, phytochemical analyses were performed using HPLC-PDA, and the total triterpene content in VDSE was determined. At 2000 mg/kg, VDSE did not induce acute toxicity. In mice treated with different VDSE doses (500, 1000, or 2000 mg/kg), no chromosomal damages or altered ratios of polychromatic erythrocytes to total erythrocytes were noted. VDSE also did not induce toxicity to G. mellonela and C. elegans as evidenced by 100% survival. The extract contained a total triterpene content of 780 mg g (39%). Since VDSE exerts a beneficial role in treating infections, it is essential to determine the risks associated with consuming these plant species to establish safety. Consequently, the present results expand knowledge regarding VDSE chemical quality control and safety.

Saxitoxin (STX), a potent neurotoxin produced by cyanobacteria, has not been comprehensively investigated with respect to genotoxic potential, especially in freshwater environments. This study aimed to characterize the genotoxic potential of STX obtained from Raphidiopsis. raciborskii cultures using in vitro and in silico approaches. Mutagenic potential was determined through the Ames test with Salmonella typhimurium strains TA98, TA100, and TA102. DNA damage and chromosomal instability were assessed in human glioblastoma U87-MG cells using the comet and cytokinesis-block micronucleus cytome (CBMN-Cyt) assay, respectively. In addition, systems biology tools were applied to explore STX interactions with genes involved in DNA damage response pathways. Data demonstrated no marked mutagenic activity in the Ames test across tested concentrations (0.625-10 µg/L). However, significant DNA damage and increased micronucleus (MN) formation were observed at 2.5, 5, or 10 µg/L in U87-MG cells, without accompanying cytotoxicity. In silico analysis identified interactions between STX and key proteins, including P53, CDK5, and GSK3B, indicating pathways related to DNA damage, cell cycle regulation, and neurogenesis. These findings suggest that STX from freshwater cyanobacteria might induce genotoxic effects at environmentally relevant concentrations. The integration of in vitro and computational data supports the need for regulatory monitoring of STX in drinking water and emphasizes the relevance of neural cell-based models in assessing cyanotoxin-related adverse risks.

The genus Mimosa (Fabaceae), includes approximately 540 species, some of which are popularly known as "Jurema" and are extensively used in traditional medicine. This study aimed to identify the chemical constituents and examine the antioxidant, anticholinesterase, and cytotoxic activities of ethanolic extracts obtained from the stem bark of Mimosa pteridifolia, M. tenuiflora, and M. verrucosa. Plant materials were subjected to ethanol extraction, followed by (ultra performance liquid chromatography with quadrupole time-of-flight (UPLC-QTOF-MS/MS) analysis and qualitative phytochemical screening. Antioxidant activity was assessed using the DPPH radical assay, while total phenol and flavonoid contents were quantified using the Folin-Ciocalteu and aluminum trichloride (AlCl₃) complexation methods, respectively. Anticholinesterase activity was determined using the Ellman method, and cytotoxicity by the MTT method utilizing human colorectal adenocarcinoma (HCT-116), human breast adenocarcinoma (MDA-MB-231), and non-tumor mouse fibroblast (L929) cell lines. After analysis of the extracts, 14 compounds, including indole and a new phytoindole alkaloid (10), tannins, proanthocyanidins, flavonoids, and triterpene saponins were identified. While all extracts demonstrated significant antioxidant and anticholinesterase properties. M. tenuiflora exhibited the highest total phenol content (570.06   ±   5.7 GAE/g) while all extracts contained low flavonoid content. Further, M. tenuiflora exhibited the strongest effects (EC₅₀ = 76.87   ±   1.41 μg/ml for antioxidant and IC₅₀ = 2.35 mg/ml for anticholinesterase activity). Importantly, none of the extracts demonstrated significant cytotoxicity against the tested cell lines, indicating non-toxicity to non-cancer cells. Data demonstrated a greater understanding of the chemical composition of three Mimosa species and indicates potential anticholinesterase and antioxidant activities, particularly extracts of M. tenuiflora.

Chronic inflammatory bowel diseases (IBDs), particularly colitis, remain a major health burden due to the limitations of current therapies, including adverse effects and diminishing efficacy. Artemisia herba-alba (A. herba-alba), a medicinal plant traditionally used in North Africa and the Middle East, holds promise as a natural anti-inflammatory agent. However, the efficacy of A. herba-alba against chronic colitis is underexplored. The aim of this study was to undertake a comprehensive investigation combining phytochemical analysis, ADMET predictions, toxicity assessment, and in vivo evaluation. High-performance liquid chromatography (HPLC) detected 5 major bioactive compounds: nicotinic acid, gallic acid, rutin, catechin, and caffeic acid. ADMET profiling using SwissADME, ADMET-AI, and ProTox-II indicated favorable pharmacokinetic properties and low predicted toxicity (LD₅₀ >2000 mg/kg). A 30-day subchronic toxicity study in mice treated with up to 1000 mg/kg of extract confirmed its safety, with no mortality, behavioral changes, or organ abnormalities. Therapeutic efficacy was evaluated in a carrageenan-induced subchronic colitis murine model. Oral administration of A. herba-alba extract (500 mg/kg) significantly alleviated colitis, preserving colon length and improving mucosal architecture. Histological analysis revealed reduced crypt damage and inflammatory cell infiltration. Taken together, these results confirm the favorable safety profile and beneficial therapeutic potential of A. herba-alba, supporting its development as a multi-targeted, natural treatment for chronic colitis.

Gamma-aminobutyric acid (GABA), a non-protein amino acid widely distributed in several natural products, exhibits potential for regulation of various cancers. The aim of this study was to examine the suppressive effect of GABA-containing product (GCP) derived from Lactobacillus fermentum-fermented rice bran on MCF-7 cell breast cancer cells. The MTT assay was used to measure cytotoxicity following exposure to GCP. Further, qPCR analysis was utilized for assessment of target gene expression, while flow cytometry was employed for determination of apoptosis and cell cycle arrest. Data demonstrated that GCP significantly suppressed migration of MCF-7 breast cancer cells at a non-cytotoxic concentration of 400 µg/ml. In addition, GCP downregulated the gene and protein expression of matrix metalloproteinase (MMP)-2 and -9 in these cells. Notably, treatment of GCP produced cell cycle arrest in phase of G2/M and induced an early apoptotic process via upregulation of caspase-8, -9, and Bax expression. Evidence indicates that GCP may be considered as a promising food ingredient for management of breast cancer metastasis.

Infants' and children's health is particularly susceptible to exposure to various environmental contaminant insults as their immune systems are immature and daily activities may present differing patterns of exposure. Although some studies noted an association between long-term exposure to ambient fine particulate matter (PM_2.5) and increased infant mortality frequency, few investigations examined the relationship between reduced exposure to PM_2.5 and changes in infant mortality rates. Therefore, this study was conducted to determine whether diminished levels of PM_2.5 in Taiwan improved post-neonatal infant health. Avoidable premature post-neonatal infant mortality was employed as an indicator of health impact. A mean value was calculated for annual PM_2.5 levels across Taiwan for the years 2006, 2015, and 2023. Using these averages and following WHO methodology, differences in the number of post-neonatal infant deaths attributed to ambient PM_2.5 exposure were determined. PM_2.5 concentrations fell markedly throughout Taiwan over the 20-year study period. In conjunction with this decline, a lowered health burden was noted, which was represented as a fall in post-neonatal infant deaths (14.8% in 2006 to 10.3% in 2023). Reduction in annual levels of PM_2.5 to 10 µg/m³ was associated with a decrease in the total burden of post-neonatal infant mortality occurrence, with a 5.58-9.31% decline in PM_2.5-related deaths during that period. Evidence indicates that exposure to PM_2.5 air pollution poses a significant burden to Taiwan children's health. Our findings indicate that the potential benefits to children's health need to be given importance when considering improving air quality policies.

The International Agency for Research on Cancer classified fine particulate matter (PM_2.5) air pollution as carcinogenic to humans (Group I). Although PM_2.5 exposure has been associated with lung cancer occurrence, few studies investigated this association with non-lung cancer. Colorectal cancer (CRC) is the third leading cause of cancer deaths both among men and women. In Taiwan, deaths attributed to CRC vary considerably across townships, suggesting involvement of the environment. The aim of this study was to examine the association between long-term ambient PM_2.5 exposure and deaths attributed to CRC in 66 municipal areas across Taiwan. Annual PM_2.5 levels were compared against age-standardized CRC mortality rates in male and female residents of these municipalities from 2012 to 2021. Annual PM_2.5 levels of different municipalities were sub-divided into tertiles. Adjusted risk ratio (RR) was calculated by multiple regression analyses, controlling for municipal lung cancer deaths, urbanization level, annual average household income, and density of physicians in the municipal areas. For males, adjusted RRs for CRC death were 1.1 (95% CI = 1.05-1.15) for municipalities with PM_2.5 levels ranging from 18.96 to 25.19 µg/m³and 1.15 (95% CI = 1.1-1.21) for levels ranging from 25.2 to 29.48 µg/m³, respectively, compared to those areas belonging to the lowest tertiles. Our analysis of trend suggested that risk of CRC-related death paralleled increases PM_2.5 levels in males. For females, adjusted RRs were 1.18 (95% CI = 1.12-1.25) and 1.12 (95% CI = 1.06-1.19), respectively. Evidence indicated that long-term exposure to PM_2.5 may elevate the risk of CRC-related death in both men and women in Taiwan.

Neuropathic pain (NP) consists of a range of unpleasant sensations attributed to a lesion or a disease of the somatosensory nervous system. It is important to note that the sensations initiated by NP are debilitating and adversely affect quality of life; however, the underlying mechanisms involved in the occurrence and development of this type of pain remain to be determined. Previously data demonstrated that inhibition of TLR4/NF-κB signaling pathway diminished the adverse consequences attributed to NP. Thus, the purpose of this study was to examine whether saponins derived from Tribulus terrestris might exert an analgesic effect on NP in rats using a chronic constriction injury (CCI) involving sciatic nerve. Male rats were randomly divided into Sham, CCI, low 100 mg/kg T. terrestris, high 200 mg/kg T. terrestris, and compared to pregabalin 10 mg/kg, the recognized first line of defense in NP. Three days after surgery, rats were treated with sham control (water) or drugs. The paw mechanical withdrawal threshold (PMWT) and thermal latency (TL) of rats were measured 1 day before operation and 3, 7, and 10 days after. Nissl staining was used to observe the morphology and Western Blot to detect protein expression of NF-κB and TLR4 on the 10th day after operation. ELISA was employed to detect levels of IL-1β, IL-6, and TNF-ɑ in spinal cord. CCI significantly decreased PMWT and TL. In CCI neurons and glial cells in the spinal dorsal horn were deeply stained with swelling and atrophy observed. The protein expression levels of NF-κB and TLR4 in the spinal dorsal horn of the injured side were significantly increased accompanied by elevated levels of inflammatory mediators IL-1β, IL-6, and TNF-ɑ. Treatment with low 100 mg/kg or high 200 mg/kg T. terrestris or pregabalin reduced effects of CCI on PMW, TL, histopathological changes as well as levels of inflammatory cytokines IL-1β and IL-6 associated with inhibition of TLR4/NF-κB pathway. Data suggest that T. terrest exerts an analgesic effect on peripheral NP which involves TLR4/NF-κB pathway inhibition.

The increase in water and soil contamination by potentially toxic elements (PTEs) constitutes a major environmental concern. Amongst these elements, cadmium (Cd) stands out due to its high mobility in both soil and plant vascular tissue. Consequently, effective strategies for PTE removal are urgently needed. This study aimed to examine the growth, anatomical and cellular traits, chlorophyll fluorescence, macro- and micronutrients content of Pau-Viola (Citharexylum myrianthum Cham.) seedlings exposed to different Cd concentrations 0.25, 0.5, or 0.75 μmol/kg in soil. C. myrianthum seedlings exposed to Cd exhibited minimal alterations in morphophysiological attributes. Cadmium was predominantly retained in the root system with limited translocation to the shoots, thereby preserving growth and nutritional balance. The lower Cd accumulation in the leaves helped maintain the integrity of the photosynthetic electron transport chain and the chlorophyll index, resulting in only minor changes in chlorophyll a fluorescence transients. The observed tolerance of C. myrianthum to Cd-initiated toxicity suggests metallic potential use in reforestation programs for Cd-contaminated areas, as the species demonstrated resilience and physiological stability under such conditions.