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

{"title":"Effect of knockdown LncRNA SNHG1 on autophagic function in SH-SY5Y cells: a model of Alzheimer's disease (AD).","authors":"Xiao-Xu Li, Xu-Sheng Yan, Chun-Jie Zhang, Yi-Chi Zhang, Xiao-Jing Su, He Zhang, Jin Yang, Yi-Long Zhang, Zhi-Ying Zhao","doi":"10.1080/15287394.2025.2474634","DOIUrl":"10.1080/15287394.2025.2474634","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"1-9"},"PeriodicalIF":2.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of safety and efficacy of Brazilian brown propolis from <i>Araucaria sp</i>. in preventing colon cancer.","authors":"Karoline Soares de Freitas, Iara Silva Squarisi, Letícia Teixeira Marcos de Souza, Saulo Duarte Ozelin, Lucas Teixeira de Souza Oliveira, Victor Pena Ribeiro, Jairo Kenupp Bastos, Denise Crispim Tavares","doi":"10.1080/15287394.2024.2431921","DOIUrl":"10.1080/15287394.2024.2431921","url":null,"abstract":"<p><p>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 <i>Araucaria sp</i>. 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.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"196-208"},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Force-induced tissue compression alters circulating hormone levels and biomarkers of peripheral vascular and sensorineural dysfunction in an animal model of hand-arm vibration syndrome.","authors":"Kristine Krajnak, Stacey Waugh, Christopher Warren, Phillip Chapman, Xueyan Xu, Daniel Welcome, Maryann Hammer, Diana Richardson, Renguang Dong","doi":"10.1080/15287394.2024.2428599","DOIUrl":"10.1080/15287394.2024.2428599","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"175-195"},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thirty years of surveillance of depleted uranium-exposed Gulf War veterans demonstrate continued effects to bone health.","authors":"Melissa A McDiarmid, Sammy Almashat, Marianne Cloeren, Marian Condon, Marc Oliver, Tracy Roth, Patricia Gucer, Clayton H Brown, Hilary B Whitlatch, Kenneth C Wang, Jigar B Patel, Moira Dux, Terry Lee-Wilk, Dong Lee, Michael R Lewin-Smith, Hanna Xu, Frederick G Strathmann, John A Koslowski, Maria A Velez-Quinones, Joanna M Gaitens","doi":"10.1080/15287394.2024.2432021","DOIUrl":"10.1080/15287394.2024.2432021","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"209-225"},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of black ginseng on testicular toxicity induced by Di-<i>n</i>-butyl phthalate in rats.","authors":"Chan Ju Park, Chi Rim Sung, Junmin An, Yu Jin Lee, In Ah Oh, Seon Kim, Yeo Rim Park, Seung Jun Kwack","doi":"10.1080/15287394.2024.2428596","DOIUrl":"10.1080/15287394.2024.2428596","url":null,"abstract":"<p><p>Di-<i>n</i>-butyl phthalate (DBP) is a phthalate-based material used as a plasticizer to soften polyvinyl chloride, and classified as an endocrine disruptor with antiandrogen effects. Exposure to DBP induces oxidative stress in rat testes, resulting in testicular toxicity. Black ginseng (BG) exhibits a higher antioxidant activity than white or red ginseng following repeated heat treatment and processing. This study aimed to investigate whether the antioxidant activity of BG might protect against DBP-induced testicular toxicity in juvenile Sprague-Dawley rats. A significant decrease in testicular weight was observed in most groups treated with DBP alone or in combination with BG. However, a significant testicular weight increase was detected after exposure to BG (10 ml/kg) + DBP (500 mg/kg). The epididymal weight was significantly reduced with associated histological changes including irregular arrangement, atrophy of seminiferous tubules and Sertoli cells, and Leydig cell damage following exposure to DBP alone as well as BG (2.5 ml/kg) + DBP (500 mg/kg). However, no marked changes were observed in the shape of seminiferous tubules in control and BG + DBP groups. A significant decrease in serum testosterone levels was found after exposure to DBP, but no marked alterations in the BG + DBP groups. Protein expression levels of nuclear factor erythroid-derived 2-related factor (Nrf2), NAD(P)H dehydrogenase 1 (NQO1), and, heme oxygenase-1; (HO-1) were significantly higher following DBP treatment, but lowered in the BG + DBP groups. Evidence indicates that BG exerts a protective effect against DBP-induced testicular toxicity in rats.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"152-161"},"PeriodicalIF":2.3,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of biocide chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) mixture on C2C12 muscle cell damage attributed to mitochondrial reactive oxygen species overproduction and autophagy activation.","authors":"Donghyun Kim, Yusun Shin, Yong-Wook Baek, HanGoo Kang, Jungyun Lim, Ok-Nam Bae","doi":"10.1080/15287394.2024.2420083","DOIUrl":"10.1080/15287394.2024.2420083","url":null,"abstract":"<p><p>The mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT) is a biocide widely used as a preservative in various commercial products. This biocide has also been used as an active ingredient in humidifier disinfectants in South Korea, resulting in serious health effects among users. Recent evidence suggests that the underlying mechanism of CMIT/MIT-initiated toxicity might be associated with defects in mitochondrial functions. The aim of this study was to utilize the C2C12 skeletal muscle model to investigate the effects of CMIT/MIT on mitochondrial function and relevant molecular pathways associated with skeletal muscle dysfunction. Data demonstrated that exposure to CMIT/MIT during myogenic differentiation induced significant mitochondrial excess production of reactive oxygen species (ROS) and a decrease in intracellular ATP levels. Notably, CMIT/MIT significantly inhibited mitochondrial oxidative phosphorylation (Oxphos) and reduced mitochondrial mass at a lower concentration than the biocide amount, which diminished the viability of myotubes. CMIT/MIT induced activation of autophagy flux and decreased protein expression levels of myosin heavy chain (MHC). Taken together, CMIT/MIT exposure produced damage in C2C12 myotubes by impairing mitochondrial bioenergetics and activating autophagy. Our findings contribute to an increased understanding of the underlying mechanisms associated with CMIT/MIT-induced adverse skeletal muscle health effects.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"137-151"},"PeriodicalIF":2.3,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"cGAS/STING pathway modulation in polyhexamethyleneguanidine phosphate-induced immune dysregulation and pulmonary fibrosis using human monocytic cells (THP-1) and male C57BL/6 mice.","authors":"Jin Kyung Seok, Jung In Jee, Minwoo Jeon, Donghyun Kim, Kyu Hyuck Chung, Ha Ryong Kim, Yong-Wook Baek, HanGoo Kang, Jungyun Lim, Ok-Nam Bae, Joo Young Lee","doi":"10.1080/15287394.2024.2432020","DOIUrl":"10.1080/15287394.2024.2432020","url":null,"abstract":"<p><p>Polyhexamethyleneguanidine phosphate (PHMG), a widely used antimicrobial agent, has been implicated in humidifier disinfectant-associated lung injuries (HDLI). PHMG exposure suppressed interferon regulatory factor 3 (IRF3) activation and interferon-β (IFN-β) expression induced by a cGAS agonist or a STING agonist in human monocytic cells (THP-1), which are known to transition to alveolar macrophages during pulmonary fibrosis development. However, the mechanisms underlying PHMG-induced pulmonary toxicity in lung remain unclear. Thus, it was of interest to investigate the effects of PHMG on the innate immune system in male C57BL/6 mouse, focusing on the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway and potential role in pulmonary fibrosis. Intratracheal administration of PHMG (1 or 2 mg/kg) in mice resulted in lung fibrosis, as evidenced by H&E staining with Szapiel scoring, Masson's trichrome staining with Ashcroft scoring, and increased mRNA levels of TGF-β and collagen type I. Interestingly, lower dose of PHMG enhanced IFN-β production in the lungs, whereas higher dose decreased IFN-β levels, indicating a biphasic effect that initially promotes inflammation but ultimately impairs host defense mechanisms, leading to pulmonary fibrosis. Our findings demonstrate the critical role of the cGAS/STING pathway in PHMG-induced mouse lung injury and suggest that targeting this pathway might serve as a potential therapeutic strategy for treating pulmonary fibrosis.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"162-174"},"PeriodicalIF":2.3,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of skin sensitization potential of zinc oxide, aluminum oxide, manganese oxide, and copper oxide nanoparticles through the local lymph node assay: 5-bromo-deoxyuridine flow cytometry method.","authors":"Anju Maharjan, Ravi Gautam, GiYong Lee, DongYoon Kim, DaEun Lee, Manju Acharya, HyoungAh Kim, Yong Heo, ChangYul Kim","doi":"10.1080/15287394.2024.2357466","DOIUrl":"10.1080/15287394.2024.2357466","url":null,"abstract":"<p><p>The advent of nanotechnology has significantly spurred the utilization of nanoparticles (NPs) across diverse sectors encompassing industry, agriculture, engineering, cosmetics, and medicine. Metallic oxides including zinc oxide (ZnO), copper oxide (CuO), manganese oxide (Mn₂O₃), and aluminum oxide (Al₂O₃), in their NP forms, have become prevalent in cosmetics and various dermal products. Despite the expanding consideration of these compounds for dermal applications, their potential for initiating skin sensitization (SS) has not been comprehensively examined. An <i>in vivo</i> assay, local lymph node assay: 5-bromo-2-deoxyuridine-flow cytometry method (LLNA: BrdU-FCM) recognized as an alternative testing method for screening SS potential was used to address these issues. Following the OECD TG 442B guidelines, NPs suspensions smaller than 50 nm size were prepared for ZnO and Al₂O₃ at concentrations of 10, 25, and 50%, and Mn₂O₃ and CuO at concentrations of 5, 10, and 25%, and applied to the dorsum of each ear of female BALB/c mice on a daily basis for 3 consecutive days. Regarding the prediction of test substance to skin sensitizer if sensitization index (SI)≥2.7, all 4 NPs were classified as non-sensitizing. The SI values were below 2.06, 1.33, 1.42, and 0.99 for ZnO, Al₂O₃, Mn₂O₃, and CuO, respectively, at all test concentrations. Although data presented were negative with respect to adverse SS potential for these 4 NPs, further confirmatory tests addressing other key events associated with SS adverse outcome pathway need to be carried out to arrive at an acceptable conclusion on the skin safety for both cosmetic and dermal applications.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"95-105"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass spectrometry (MS)-based metabolomics of plasma and urine in dry eye disease (DED)-induced rat model.","authors":"Hyang Yeon Kim, Jung Dae Lee, HongYoon Kim, YuJin Kim, Jin Ju Park, Soo Bean Oh, Hyeyoon Goo, Kyong Jin Cho, Kyu-Bong Kim","doi":"10.1080/15287394.2024.2393770","DOIUrl":"10.1080/15287394.2024.2393770","url":null,"abstract":"<p><p>Dry eye disease (DED) is an ophthalmic disease associated with poor quality and quantity of tears, and the number of patients is steadily increasing. The aim of this study was to determine plasma and urine metabolites obtained from DED scopolamine animal model where dry eye conditions (DRY) are induced. It was also of interest to examine whether DED (scopolamine) rat model was exacerbated by treatment with benzalkonium chloride (BAC). Subsequently, plasma and urine metabolites were analyzed using liquid chromatography (LC) and gas chromatography (GC)-mass spectrometry (MS), respectively. Data demonstrated that DED indicators such as tear volume, tear breakup time (TBUT), and corneal damage in the DED groups (DRY and BAC group) differed from those of control (CON). Similar results were noted in inflammatory factors such as interleukin (IL-1β), IL-6, and tumor necrosis factor (TNF)-α. In the partial least squares-discriminant analysis (PLS-DA) score plots, the three groups were distinctly separated from each other. In addition, the related metabolites were also associated with these distinct separations as evidenced by 9 and 14 in plasma and urine, respectively. Almost all of the selected metabolites were decreased in the DRY group compared to CON, and the BAC group was lower than the DRY. In plasma and urine, lysophosphatidylcholine/lysophosphatidylethanolamine, organic acids, amino acids, and sugars varied between three groups, and these metabolites were related to inflammation and oxidative stress. Data suggest that treatment with scopolamine with/without BAC-induced DED and affected the level of systemic metabolites involved in inflammation and oxidative stress.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"122-135"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MC-LR induces and exacerbates Colitis in mice through the JAK1/STAT3 pathway.","authors":"Xiaodie Zhou, Yue Yang, Canqun Yan, Shuidong Feng, Chunhua Zhan","doi":"10.1080/15287394.2024.2443227","DOIUrl":"https://doi.org/10.1080/15287394.2024.2443227","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a complex gastrointestinal disorder attributed to genetic and environmental factors. Microcystin-leucine-arginine (MC-LR) is an environmental toxin that accumulates in the gut and produces intestinal damage. The aim of this study was to investigate the effects of exposure to MC-LR on development and progression of IBD as well examine the underlying mechanisms of microcystin-initiated tissue damage. Male C57BL/6 mice were treated with either MC-LR alone or concurrently with dextran-sulfate sodium (DSS). Mice were divided into 4 groups (1): PBS gavage (control, CT) (2); 200 μg/kg MC-LR gavage (MC-LR) (3); 3% DSS Drinking Water (DSS); and (4) 3% DSS Drinking Water + 200 μg/kg MC-LR gavage (DSS + MC-LR). The mice in each experimental group exhibited reduced body weight, shortened colon length, increased disease activity index (DAI) score, a disrupted intestinal barrier, and elevated levels of proinflammatory cytokines compared to control. Compared to the group treated with MC-LR alone, colitis symptoms were exacerbated following combined exposure to both DSS and MC-LR. Subsequent experiments confirmed that MC-LR or DSS increased protein phosphorylation levels of Janus Kinase1 (JAK1) and Signal Transducer and Activator of Transcription3 (STAT3). Compared to group treated with MC-LR alone, the combined treatment of DSS and MC-LR also significantly upregulated the expression of related proteins. In conclusion, our study indicates that MC-LR-induced colitis involves activation of JAK1/STAT3 signaling pathway and that MC-LR exacerbates DSS-induced colitis through the same pathway.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"1-11"},"PeriodicalIF":2.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}