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.

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 covalent binding of sensitizer to skin proteins is referred to as key event 1 of the adverse outcome pathway in skin sensitization. Recently, N-acetyl-L-cysteine methyl ester (NACME) was demonstrated to react selectively with skin sensitizers in vitro, such that NACME might be applied as an electron donor in developing a spectrophotometric test for determining skin sensitization potential of chemicals. To avoid possible color interference by certain test chemicals, a fluorometric test method was developed using monobromobimane (mBBr), a thiol-reactive fluorescent probe. Similar to previous methods utilizing the reaction of NACME with sensitizers, unreacted NACME occurred which was then measured fluorometrically using mBBr, rather than 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB). Following the optimization of test conditions, the same 64 test chemicals used in the previous study were tested to determine the predictive capacity of the current method. Results showed a predictive capacity of 81.1% sensitivity, 81.5% specificity, and 81.3% accuracy with a cutoff NACME depletion of 11.3%. Although these values were relatively lower than the previous test using DTNB, the results were still comparable to OECD-approved test methods and that color interference issues might be ruled out. Data demonstrated that NACME might be viewed as a candidate for identifying reactive skin sensitizers. Further, this method might be considered as a complementary or supportive method to the former DTNB assay as a screening tool for assessing the tendency of a chemical to initiate skin sensitization in case of test chemicals showing color interference.

Brazilian propolis produced by honeybees have been widely studied, but few data exist regarding the safety and pharmacological potential of this natural product. The aim of the present study was to examine the toxicity, genotoxicity, and chemoprevention effects attributed to exposure to the brown propolis hydroalcoholic extract (BPHE) of Araucaria sp. Acute oral toxicity test was conducted using Wistar Hannover rats, demonstrating that the highest dose tested (2,000 mg/kg b.w.) produced no apparent adverse effects or lethality. The micronucleus (MN) genotoxicity test was conducted using peripheral blood from Swiss mice, which also noted that BPHE did not induce significant chromosomal damage. It is of interest that BPHE at a dose of 12 mg/kg b.w. exhibited antigenotoxic effects against the doxorubicin (DXR)-induced damage. However, BPHE did not influence the depletion of reduced glutathione induced by DXR in mice. It is noteworthy that BPHE exerted chemopreventive effects at doses 6, 12, and 24 mg/kg b.w. The determination of this effect of BPHE on colon carcinogenesis was examined using aberrant crypt foci (ACF) as evidenced by histological analysis. The colons of animals treated with BPHE (12 mg/kg b.w.) exhibited a significant reduction in staining for proliferating cell nuclear antigen (PCNA) and cyclooxygenase-2 (COX-2) protein following 1,2-dimethylhydrazine (DMH)-and BPHE combined treatments. Hence, it is conceivable that the anti-inflammatory activity of the chemical constituents of BPHE are involved in its chemopreventive action against colon carcinogenesis as evidenced from ACF assay. Therefore, BHPE was found to be a safe product, without any apparent significant acute adverse risk. Further, the extract exhibited antigenotoxic and anticarcinogenic activities which may be considered for beneficial uses in colon carcinogenesis.

Workers regularly using vibrating hand tools may develop a disorder referred to as hand-arm vibration syndrome (HAVS). HAVS is characterized by cold-induced vasospasms in the hands and fingers that result in blanching of the skin, loss of sensory function, pain, and reductions in manual dexterity. Exposure to vibration induces some of these symptoms. However, the soft tissues of the hands and fingers of workers are compressed as a result of the force generated when a worker grips a tool. The compression of these soft tissues might also contribute to the development of HAVS. The goal of this study was to use an established rat tail model to determine the mechanisms by which compression of the tail tissues affects (1) the ventral tail artery (VTA) and ventral tail nerves (VTN), (2) nerves and sensory receptors in the skin, (3) dorsal root ganglia (DRG), and (4) spinal cord. Tissue compression resulted in the following changes (1) circulating pituitary and steroid hormone concentrations, (2) expression of factors that modulate vascular function in the skin and tail artery, and (3) factors associated with nerve damage, DRG, and spinal cord. Some of these observed effects differed from those previously noted with vibration exposure. Based upon these findings, the effects of applied force and vibration are different. Studies examining the combination of these factors might provide data that may potentially be used to improve risk assessment and support revision of standards.

During the spring of 2024, 33 members of a group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents were seen at the Baltimore VA Medical Center for surveillance related to their combat exposure. The cohort was assessed with a protocol which includes exposure monitoring for total and isotopic uranium (U) concentrations in urine and a comprehensive assessment of health outcomes including measures of bone metabolism and bone mineral density (BMD). An audiometry examination of the cohort was added to assess for acoustic trauma and toxic metal effects in this surveillance episode marking over 30 years since this exposure event. Elevated urine U concentrations were detected in cohort members with retained DU shrapnel fragments. In addition, a measure of bone resorption, N-telopeptide, determined in urine, exhibited a significant increase in the high DU sub-group. In addition, and similar to our previous surveillance report, a significant decrease was found in bone mass in the high DU sub-group compared to the low DU sub-group. It has been 30 years since the first surveillance visit occurred. An aging cohort of military veterans continues to demonstrate few U-related adverse health effects in known target organs attributed to U toxicity exposure. The new finding of impaired BMD in older cohort members has now been detected in three consecutive surveillance visits. This is a biologically plausible outcome related to the diminished bone mass in those with an elevated DU burden in combination with advancing age. The accumulating U burden derived from fragment absorption over time and the effect of aging on bone mineral loss recommends that our surveillance efforts need to continue. Our findings enable early detection of bone effects and other signs of target organ insult, which may occur when tissue injury thresholds are reached in the future and thus, permitting indicated medical management.

Cerebral ischemia-reperfusion injury (CIRI) is a prevalent clinical complication associated with reperfusion following ischemic stroke resulting in neuronal damage and cognitive impairment. Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist with sedative, and analgesic properties, is frequently utilized as a sedative anesthetic in clinical surgeries, and believed to play a crucial role in the prognosis of patients suffering from CIRI. However, the mechanism underlying DEX in CIRI remains to be determined. This study aimed to investigate the neuroprotective effects of Dex in rats suffering from CIRI. In the treatment group, DEX (50 µg/kg) was administered intraperitoneally 30 min prior to surgery. Middle cerebral artery occlusion (MCAO) used as a model of CIRI occurred with cerebral artery occlusion for 2 h was followed by reperfusion with blood for 24, 72, 120 or 168 h. Neurological function as assessed by the Longa neurological function score test demonstrated significantly reduced neurological scores and increased % infarct size in MCAO group which was blocked by DEX suggesting that DEX might be effective in treating ischemic stroke. In the MCAO animals, 2,3,5-triphenyltetrazolium chloride (TTC) showed large marked areas of cerebral infarction which were diminished in size by DEX. Using Western blot analysis, results showed that in MCAO rats protein expression levels of TNF-α and IL-6 were increased accompanied by reduced protein expression levels of PI3K/AKT signaling pathway. DEX pretreatment reversed the effects of MCAO as evidenced by decrease in protein expression levels of TNF-α and IL-6 associated with elevated protein expression levels of PI3K/AKT/NF-κB signaling pathway. Data demonstrated that DEX pretreatment improved the neuromotor performance and cognitive functions in animals suffering from consequences of MCAO by diminishing inflammation and activation of the PI3K/AKT/NF-κB signaling pathway.

Hazardous noise is a pervasive environmental pollutant with significant adverse health impacts on auditory and non-auditory organs. It is noteworthy that even acute noise exposure might pose immediate detrimental effects to various organs. However, the long-term effects of acute noise exposure remain largely unknown. This study aimed to explore this gap by randomizing 12 Long-Evans rats into acute noise and control groups. The acute noise regimen was a single three-hr wideband noise (12.5 hz-20 kHz) at 105 dB SPL_peak. Four weeks following exposure cessation, animals from both groups were sacrificed. Genomic DNA and RNA were extracted from the cochlea, brain, heart, and liver. Long-target polymerase assays and real-time quantitative polymerase chain reactions were performed to assess DNA integrity and p53-targeted gene expression, respectively, with results being compared between the two groups. Data demonstrated that noise-induced changes in DNA integrity depended upon organ type, with significant interaction effects between treatment conditions (noise or control) and organ type for nuclear and mitochondrial DNA integrity. In addition, there were significant changes in p53-targeted gene expression between noise-exposed and control in all tested organs. In conclusion, the long-term impact of acute hazardous noise exposure on DNA integrity was complex, highlighting organ-specificity in response to noise. However, such noise significantly altered p53-targeted genes systemically, indicating ongoing cellular stress. Overall, these results suggest that acute exposure to hazardous noise may have potential long-term adverse consequences. Immediate care following exposure might mitigate possible impacts on long-term health.

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.

Natural products, although frequently associated with beneficial effects and considered harmless, still require thorough analysis; therefore, their bioactive compounds need to be used with caution. Biological assays using plant models represent an appropriate alternative for evaluating the cytogenotoxicity associated with these products. In this study, the phyto- cytotoxic potential of extracts from the bark of Rhamnus purshiana DC. a species widely used for treatment of constipation was investigated due to its anthraquinone content. To this end, seeds of Lactuca sativa L. were employed in phyto-cytogenotoxic assays under chronic exposure to lyophilized and spray-dried extracts. The results showed that extraction methods directly influence the phytochemical composition and biological effects of the extracts. Both extracts exhibited high anthraquinone content, expressed as cascaroside A, with concentrations ranging from 45.65 to 72.17 μg/ml. The spray-dried extract demonstrated a more potent inhibitory effect on morphological parameters, such as root elongation, while lyophilized extract exhibited higher cytotoxicity. Both extracts induced mitodepressive effects and aneugenic damage. Notably, the lyophilized extract induced a 300% increase in mitotic abnormalities compared to control, with a higher frequency of C-metaphases and stickiness. Although R. purshiana is widely used in traditional medicine, the scarcity of studies on cascaroside A raises concerns regarding socio-environmental safety and continued use of this species in dietary supplements.