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

{"title":"Effect of chronic low-dose microcystin-LR exposure on jejunum apoptosis via RAF/ERK signaling pathway in mouse.","authors":"Sihong Long, Cong Wen, Wen Zeng, Yue Yang, Fei Yang","doi":"10.1080/15287394.2024.2435631","DOIUrl":"10.1080/15287394.2024.2435631","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"291-300"},"PeriodicalIF":2.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820330","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":"Cytotoxic effects of the standardized extract from <i>Curcuma aromatica</i> Salisb. rhizomes via induction of mitochondria-mediated caspase-dependent apoptotic pathway and p21-mediated G0/G1 cell cycle arrest on human gastric cancer AGS cells.","authors":"Chinh Chung Doan, Thanh Long Le, Nguyen Quynh Chi Ho, Thi Thuy Nguyen, Nghia Quang Huy Hoang, Phuc Chien Le, Nguyen Tu Linh Le, Thi Linh Giang Tran, Thi Phuong Thao Nguyen, Nghia Son Hoang","doi":"10.1080/15287394.2024.2433577","DOIUrl":"10.1080/15287394.2024.2433577","url":null,"abstract":"<p><p><i>Curcuma aromatica</i> Salisb. (<i>C. aromatica</i>) 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 <i>C. aromatica</i> 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 <i>C. aromatica</i> rhizome standardized extract against gastric cancer cells. The components of two major active compounds in <i>C. aromatica</i> 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 <i>C. aromatica</i> rhizomes. The two major active compounds curdione and germacrone, in the <i>C. aromatica</i> 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.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"227-249"},"PeriodicalIF":2.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786915","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":"Allelopathic activity of coffee extracts: implications for germination and initial growth in select weeds and polyploidy in <i>Lactuca sativa</i> L.","authors":"Sttela Dellyzete Veiga Franco da Rosa, Ana Luiza de Oliveira Vilela, Marcus Vinicius Prado Alves, Maria Das Graças Cardoso, Larissa Fonseca Andrade Vieira, Ana Maria Oliveira Ferreira, Leonardo M da Silva","doi":"10.1080/15287394.2024.2434952","DOIUrl":"10.1080/15287394.2024.2434952","url":null,"abstract":"<p><p>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 <i>Lactuca sativa</i> L. <i>Bidens pilosa</i> L. and <i>Cyperus rotundus</i> L. and (2) determine the induction of changes in the cell cycle of <i>L. sativa</i> 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 <i>L. sativa L</i>. and GC for <i>B. pilosa L</i>. diminished germination parameters. For <i>C. rotundus L</i>. GC extract decreased growth regardless of the concentration. An increased frequency of cell cycle alterations was observed in the root cells of <i>L. sativa</i> 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 <i>L. sativa</i> L. as well as inducing alterations in the cell cycle of <i>L. sativa</i> L.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"250-262"},"PeriodicalIF":2.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774854","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":"Element contents in edible seaweeds and assessment of human health from their consumption.","authors":"Caroline Rodrigues Albuquerque, Paulo Sergio Cardoso da Silva, Fungyi Chow, Edson Gonçalves Moreira, Vera Akiko Maihara","doi":"10.1080/15287394.2024.2435061","DOIUrl":"10.1080/15287394.2024.2435061","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"263-277"},"PeriodicalIF":2.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796377","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}