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

In recent years, the outbreak of cyanobacterial blooms has become increasingly frequent. Microcystin-LR (MC-LR), a metabolite of cyanobacteria, poses a significant threat to the ecosystem and human health. Several studies have demonstrated that MC-LR might induce renal cell apoptosis, as a consequence of tissue damage. However, the molecular mechanisms underlying MC-LR-initiated renal injury remain to be determined. This investigation aimed to determine the role of apoptosis in MC-LR-induced kidney damage and its potential underlying mechanisms using the human embryonic kidney (HEK293) cell line. The results of TUNEL and immunofluorescence assays indicated that MC-LR induced increased apoptosis in HEK293 cells. Compared to control, the mRNA expression levels of RIPK1, caspase-8, and TNF-α were elevated following incubation with MC-LR, while the mRNA expression level of Bcl-2/Bax was decreased. The protein levels of RIPK1, TNF-R1, and caspase-8 were elevated in the MC-LR-treated HEK293 cells. Data demonstrated that MC-LR induced renal cell apoptosis through activation of the TNF-R1/RIPK1 pathway, providing new insights into understanding the toxic mechanisms attributed to MC-LR.

Occupational exposure to N-hexane/2,5-hexanedione (2,5-HD) was found to adversely affect reproductive functions in females. However, there are few studies regarding the mechanisms underlying reproductive system damage initiated by 2,5-HD. Several studies demonstrated that 2,5-HD exerts hormonal dysfunctions in females by promoting apoptosis using rat ovarian granulosa cells (GCs) as a model. The endoplasmic reticulum (ER) plays a key role in cellular processes such as protein folding and modification, Ca²⁺ storage, and lipid synthesis, which are known to involve the activation of stress (ERS)-dependent m-TOR signaling pathway. Thus, the aim of this study was to examine the effects of 2,5-HD on ER and the associated activation of stress (ERS)-dependent m-TOR signaling pathway resulting in consequent apoptosis of ovarian GCs. Data demonstrated that after intraperitoneal treatment with 100, 200, or 400 mg/kg 2,5-HD for 6 consecutive weeks, 5 times per week, a decrease in body weight, ovarian weight, and relative ovary weight was found. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed that 2,5-HD promoted apoptosis of ovarian GCs, which involved enhanced relative protein expression levels of m-TOR/p-mTOR. Our findings demonstrated that 2,5-HD (1) elevated expression levels of pro-apoptosis-related genes Bax and Caspase 3, (2) decreased expression levels of the anti-apoptosis gene Bcl-2, and (3) activated the protein expression of glucose-regulatory protein 78 (GRP78), inositol-requiring enzyme-1 (IRE1), and c-Jun terminal kinase (JNK) associated with increased apoptosis. Evidence indicates that chronic exposure to 2,5-HD induced apoptosis of ovarian GCs, and the possible mechanism underlying this effect involves the ERS-dependent m-TOR signaling pathway.

Microcystin-LR (MC-LR), produced by cyanobacterial harmful algal blooms, poses a serious threat to aquatic ecosystems and human health. Biodegradation is an important method for MC-LR elimination. Aerobic biodegradation has been extensively studied and many bacteria were identified. However, few MC-degrading bacteria have been isolated from anaerobic environments, and these degradation mechanisms are poorly understood. The aim of this study was to collect anaerobic MC-degrading bacteria from lake sediments in Lake Taihu using acclimation culture to assess biodegradation. Five strains with MC-LR degradation ability were isolated, with strain A4 belonging to Citrobacter farmeri (C. farmeri). exhibiting the highest efficiency at 0.486 μg/ml/d. High-performance liquid chromatography (HPLC) identified two novel MC-LR degradation products. Further polymerase chain reaction (PCR) analysis suggested that C. farmeri A4 did not possess the known MC-degrading gene mlrABCD, suggesting the involvement of an mlrABCD-independent anaerobic degradation pathway. Data demonstrated that the bacterial strain C. farmeri A4 found in Lake Taihu exhibited high anaerobic MC-LR degradation properties, which indicated that anaerobic biodegradation may constitute an important biological method for MC-LR removal in natural environment.

Sex ratio at birth (SRB) is a simple, noninvasive way to monitor the reproductive health of a population. Apparently only a few studies have assessed the relationship between ambient air pollution and SRBs. The studies that investigated this relationship have yielded inconsistent results. Ambient air pollution levels, including particulate matter (PM_2.5) levels, have decreased in Taipei city after a mass rapid transit (MRT) system commenced operations in 1996. The aim of this study was to determine whether the changes in levels of PM_2.5 after the implementation of the MRT system in Taipei may have influenced the concurrent alterations noted in the SRB. In order to assess this potential association, annual numbers of male and female births were obtained from Taiwan's Department of Household Registration, Ministry of Interior Affairs from 1992 to 2023. Mean yearly SRBs were calculated for 4 time periods, 1992-1995, 1996-2004, 2005-2015, and 2016-2023. Linear logistic regression was employed to evaluate the variation in officially reported PM_2.5 levels during those periods and alterations in the ratios. The ratios for time periods 1 to 4 were 52.61%, 52.22%, 51.78%, and 51.67%, respectively. Compared to Period 1 (pre-MRT), the odds ratios for Periods 2, 3, and 4 were 0.98 (0.97-0.99), 0.97 (0.96-0.98), and 0.96 (0.95-0.98), respectively. The trend toward the decreased SRB was found to be gradual but significant.

Rice is considered to be moderately salt-tolerant during germination, development, and ripening stages, and environmentally sensitive during seedling and reproductive stages, which affects seedling emergence and growth, resulting in significant yield losses. Seed conditioning with chitosan has been employed as a useful tool in high-salinity environments with the aim of increasing crop productivity and quality, as well as promoting more sustainable agricultural practices. Therefore, this study aimed to examine the effect of seed conditioning with chitosan on seed germination and rice seedling growth under salinity stress. The experiment consisted of three seeds conditioning and 4 salinity levels, arranged in a completely randomized design with 4 replications. Seeds were sown on germitest paper, and the rolls were placed in a germination chamber (25 ± 2°C and 12 hr photoperiod). Germination and seedling growth parameters were determined. The high salt concentration resulted in reduced growth of rice seedlings, and exogenous application of chitosan at different concentrations and soaking times exerted no apparent adverse effect on germination and growth variables. The attenuating effect of chitosan was observed in the length of the seedlings at all the concentrations utilized. Therefore, evidence indicates that conditioning rice seeds with chitosan might serve as an alternative to mitigate the adverse effects of exposure to stress induced by high salt concentrations.

Exposure to microcysatin-LR (MC-LR) is known to result in kidney damage, however the underlying mechanisms involved in MC-LR-initiated renal injury are not known. Thus, the aim of this study was to examine the effects of exposure to MC-LR on human embryo kidney (HEK 293) cell in vitro and male C57BL/6 in vivo. In the in vitro study, HEK 293 cells were incubated with MC-LR (20 µM) for 24 hr. Treatment with MC-LR significantly increased the protein expression of RAF and ERK as well as mRNA expression levels of inflammatory cytokines TNF-α, IL-6, and IL-1β. These findings were confirmed when HEK 293 cells were co-incubated with ERK inhibitor U0126 and MC-LR demonstrating a decrease in protein expression of RAF, ERK, and mRNA levels of pro-inflammatory cytokines. Male C57BL/6 mice were intraperitoneally (ip) injected with MC-LR (20 µg/kg) daily for 21 days. Histopathological analysis demonstrated significant glomerular and tubular damage with inflammatory infiltration. The expression levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β were significantly elevated following MC-LR treatment. Administration of MC-LR asignificantly enhanced the protein phosphorylation levels of RAF and ERK. Data demonstrated that exposure to MC-LR induced morphological tissue damage and renal inflammatory reactions by activating the RAF/ERK signaling pathway.

Microcystin-LR (MC-LR), a class of cyclic heptapeptide compounds synthesized by cyanobacterial species, presents a significant risk to ecological systems and public health. Exposure to MC-LR was found to induce damage to various organs. One of the target organ systems affected by MC-LR is the gastrointestinal tract (GIT). However, the majority of studies regarding GIT focused on colorectal toxicity, with little attention paid to small intestinal toxic injuries, in particular jejunum. Thus, the aim of this study was to investigate the effects attributed to MC-LR exposure on apoptosis and underlying mechanisms utilizing a mouse jejunum injury model following chronic low-dose MC-LR treatment. A total of 40 C57BL/6 male mice were randomly divided into 4 groups with each group receiving drinking water containing 0, 1, 60, or 120 µg/L MC-LR for a duration of 12 months. Results indicated that exposure to MC-LR induced pathological alterations in jejunal tissue as evidenced by abnormal villous serration, crypt disorganization, and lymphocyte infiltration. TUNEL assays demonstrated a significant increase in apoptotic cell count in the 60 and 120 µg/L groups. The 60 and 120 µg/L MC-LR treatment groups exhibited elevated mRNA expression of Bax accompanied by significant reduction in mRNA expression of Bcl-2. The protein levels of cleaved caspase-3 were markedly elevated in the 60 and 120 µg/L MC-LR groups. The protein expression levels of p-RAF and p-ERK were significantly increased in the 60 and 120 µg/L MC-LR treatment groups. Data demonstrated suggest that the RAF/ERK signaling pathway may be involved in MC-LR- induced jejunal apoptosis.

Curcuma aromatica Salisb. (C. aromatica) is one of the traditional herbs used to treat microbial infection, skin eruption, coronary heart disease, and other diseases, including cancer. However, the inhibitory effects and underlying mechanisms of action of C. aromatica on gastric cancer cells have not yet been fully elucidated. Our study aimed to examine the possible molecular mechanisms underlying the cytotoxic effects attributed to C. aromatica rhizome standardized extract against gastric cancer cells. The components of two major active compounds in C. aromatica rhizome extract were quantitatively analyzed using a simple and validated HPLC method. Cytotoxicity was determined in different gastric cancer and non-cancer cell lines. The biological activities of the extract targeting apoptosis and cell cycle-related genes on gastric cancer AGS cells were also investigated to elucidate the mechanisms relating to the anti-proliferative effect of C. aromatica rhizomes. The two major active compounds curdione and germacrone, in the C. aromatica extract were standardized to 0.64% and 1.12% w/w, respectively. The standardized extract (CAE) exerted cytotoxic effects on various cancer cells, whereas minimal effects at equivalent doses were noted for normal cells. CAE concentration-dependently suppressed growth of gastric cancer AGS cells via induction of apoptosis. Further studies revealed that CAE treatment disrupted mitochondrial membrane potential (ΔΨm), increased Bax/Bcl-2 ratio, and cytochrome c release, resulting in activation of caspase-9/-3 and subsequent cleavage of PARP. Further, the inhibitory effects of caspase-9/-3 expression by a synthetic pan-caspase inhibitor partially protected cells against apoptosis following CAE treatment. In addition, CAE significantly promoted cell death in AGS cells via an accumulation of cells in the G0/G1 phase. This effect was associated with upregulation of the CDK inhibitor p21 and downregulation of cyclin D1, cyclin E, CDK4, and CDK2 expression. Our data indicated that CAE exerted anti-proliferative activity by activating the mitochondria-mediated caspase-dependent apoptotic pathway and arresting the p21-mediated G0/G1 cell cycle on human gastric cancer AGS cells.

Coffee beans contain compounds with allelopathic activity, such that some beans that do not meet quality standards might rather be used to obtain a natural herbicide which consequently might be employed to control undesired plants and avoid economic losses. Thus, the objectives of this study were: (1) to investigate the allelopathic effect of different concentrations of green (GC) and roasted (RC) coffee extracts on the inhibition of germination and initial growth of Lactuca sativa L. Bidens pilosa L. and Cyperus rotundus L. and (2) determine the induction of changes in the cell cycle of L. sativa L. and (3) quantify some compounds in the GC and RC extracts with possible allelopathic effects. Seeds and tubers were sown on germination paper, moistened with water or different concentrations of extracts, stored in transparent plastic boxes, and maintained in a germination chamber. Caffeine was found at higher concentrations of 79.768 and 15.532 g/L in GC and RC extracts, respectively. In general, RC extract for L. sativa L. and GC for B. pilosa L. diminished germination parameters. For C. rotundus L. GC extract decreased growth regardless of the concentration. An increased frequency of cell cycle alterations was observed in the root cells of L. sativa L. This study is the first to report that the studied extracts possess allelopathic potential, as they are effective in reducing germination and/or initial growth of weed species and L. sativa L. as well as inducing alterations in the cell cycle of L. sativa L.

Seaweed, traditionally part of the daily diet of Asian countries, has become a common dish in Western countries. In Brazil, although contributing to lesser amounts, seaweed consumption has been incorporated into the population eating habits. It is well established that seaweed contains (1) several biologically active components and (2) the ability to accumulate minerals and trace elements, both of which are essential and potentially toxic. Therefore, the objective of this study was to determine the concentrations of essential, trace and toxic elements present in edible seaweeds sold in São Paulo city market, considering the species, origin, and potential impact on the health of the consumers. Data demonstrated that the elemental distribution is characteristic of the species and due to low quantity consumption seaweed may be considered a reliable source for iodine alone.