{"title":"Contamination levels and distribution of persistent and non-persistent pollutants in paired hair, urine and serum samples from a Belgian non-occupationally exposed population.","authors":"Julien Claessens, Patrice Dufour, Nadia Dardenne, Corinne Charlier, Catherine Pirard","doi":"10.1080/15287394.2025.2451676","DOIUrl":"10.1080/15287394.2025.2451676","url":null,"abstract":"<p><p>Designing ideal human biomonitoring studies involves the selection of reliable markers of exposure in adequate biological matrix. Besides conventional matrices such as blood or urine, hair has been increasingly investigated as a promising noninvasive alternative. However, understanding the pollutant distribution between differing biological compartments is essential for reliable interpretation of data collected. Therefore, the contamination levels and the distribution of some persistent (8 perfluoroalkyl substances - PFAS - and 6 polychlorobiphenyls - PCBs) and non-persistent pollutants (2 bisphenols and 3 parabens) were investigated in paired serum and hair samples, or paired spot urine and hair samples obtained from 30 Belgian non-occupationally exposed individuals. The levels measured were close to those reported in recent larger-scale studies. PFAS, PCB and bisphenol distributions largely differed depending upon the matrix and within the same chemical family depending upon the congener. The correlation and agreement between pollutant levels in differing matrices demonstrated that the information provided is comparable only for highly chlorinated PCBs and parabens, while the classification of exposure for bisphenols was substantially different according to the matrix. The selection of the human matrix thus remains complex and might markedly bias the results obtained, especially when assessing the health risk related to chemical exposure.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"447-462"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016904","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}
Gintarė Sujetovienė, Martynas Jasas, Diana Miškelytė, Austra Dikšaitytė, Irena Januškaitienė, Giedrė Kacienė, Renata Dagiliūtė, Jūratė Žaltauskaitė
{"title":"Toxic effects of tetracycline on non-target lichen <i>Evernia prunastri</i>.","authors":"Gintarė Sujetovienė, Martynas Jasas, Diana Miškelytė, Austra Dikšaitytė, Irena Januškaitienė, Giedrė Kacienė, Renata Dagiliūtė, Jūratė Žaltauskaitė","doi":"10.1080/15287394.2024.2445081","DOIUrl":"10.1080/15287394.2024.2445081","url":null,"abstract":"<p><p>Tetracycline (TC) antibiotics are one of the class of drugs widely used in clinical practice but also constitute a significant environmental concern. However, the adverse effects of TC on non-target organisms have not been well studied. The aim of this study was to examine the influence of exposure to high levels of TC on thalli of lichens to determine the impact on (1) physiological parameters including integrity of cell membranes, photosynthetic efficiency and viability, (2) oxidative stress response such as membrane lipid peroxidation, and (3) enzymatic antioxidant activities as catalase (CAT), superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR). Data demonstrated that exposure to tetracycline did not markedly affect the lichen membrane damage as indicated by no change in conductivity. This antibiotic diminished the potential photosystem II efficiency (F<sub>V</sub>/F<sub>M</sub>) indicating enhanced susceptibility as evidenced by lower chlorophyll fluorescence and chlorophyll content. The viability of lichens exposed to high concentrations of tetracycline was significantly reduced. The concentrations of thiobarbituric acid reactive substances were markedly elevated with increasing concentrations of antibiotics. At higher TC concentrations, 500 mg/L SOD activity was significantly elevated. In the case of CAT, APX and GR, TC at higher concentrations significantly decreased these enzymic activities. The findings of this study contribute to the knowledge that TC antibiotics exert adverse ecotoxicological effects on lichens at high concentrations and provided a better understanding of the mechanisms underlying toxicity. Data also indicates that lichens may serve as an effective biomonitoring species for TC antibiotic exposure.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"395-408"},"PeriodicalIF":2.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886480","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}
Joedna Cavalcante Pereira, Rayran Walter Ramos de Sousa, Micaely Lorrana Pereira Conceição, Maria Luísa Lima Barreto do Nascimento, Ana Tárcila Alves de Almeida, Antonielly Campinho Dos Reis, Mickael Laudrup de Sousa Cavalcante, Camila Dos Reis Oliveira, Italo Rossi Roseno Martins, Francisco Leonardo Torres-Leal, Dalton Dittz, João Marcelo de Castro E Sousa, Paulo Michel Pinheiro Ferreira, Felipe Cavalcanti Carneiro da Silva
{"title":"Buthionine sulfoximine acts synergistically with doxorubicin as a sensitizer molecule on different tumor cell lines.","authors":"Joedna Cavalcante Pereira, Rayran Walter Ramos de Sousa, Micaely Lorrana Pereira Conceição, Maria Luísa Lima Barreto do Nascimento, Ana Tárcila Alves de Almeida, Antonielly Campinho Dos Reis, Mickael Laudrup de Sousa Cavalcante, Camila Dos Reis Oliveira, Italo Rossi Roseno Martins, Francisco Leonardo Torres-Leal, Dalton Dittz, João Marcelo de Castro E Sousa, Paulo Michel Pinheiro Ferreira, Felipe Cavalcanti Carneiro da Silva","doi":"10.1080/15287394.2024.2448663","DOIUrl":"10.1080/15287394.2024.2448663","url":null,"abstract":"<p><p>The chemotherapeutic drug doxorubicin (DOX) has been widely used for treating solid tumors attributed to its antiproliferative effectiveness; however, its clinical use is limited due to side effects, including cardiotoxicity, myelosuppression, and drug resistance. Combining DOX with buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, showed promising results in overcoming these adverse effects, potentially reducing the required DOX dose while maintaining efficacy. The aim of the present study was to examine the effects of different concentrations of BSO and DOX, both individually and in combination, utilizing B16/F10 (murine melanoma), SNB-19 (human glioblastoma), S180 (murine sarcoma), and SVEC4-10 (murine endothelial) cell lines. Cell viability, migration, and clonogenicity were assessed using the following assays MTT, scratch, and colony formation. Antioxidant levels of GSH, as well as activities catalase (CAT), and superoxide dismutase (SOD) were measured. BSO alone exhibited minimal cytotoxic effects, while DOX alone reduced cell viability significantly. The combination of BSO+DOX decreased IC<sub>50</sub> values for most cell lines, demonstrating a synergistic effect, especially in B16/F10, S180, and SVEC4-10 cells. BSO+DOX combination significantly inhibited cell migration and clonogenicity compared to DOX alone. While GSH levels were decreased with BSO+DOX treatment activities of CAT and SOD increased following DOX administration but remained unchanged by BSO. These results suggest that BSO may be considered a valuable tool to improve DOX therapeutic efficacy, particularly in cases of chemotherapy-resistant tumors, as BSO enhances DOX activity while potentially reducing systemic chemotherapeutic drug toxicity.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"409-431"},"PeriodicalIF":2.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016901","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}
Yin Zhang, Ying Guan, Manni Dai, Yue Yang, Fei Yang
{"title":"Microcystin-LR induces lung injury in mice through the NF-κB/NLRP3 pathway.","authors":"Yin Zhang, Ying Guan, Manni Dai, Yue Yang, Fei Yang","doi":"10.1080/15287394.2024.2443525","DOIUrl":"10.1080/15287394.2024.2443525","url":null,"abstract":"<p><p>Microcystin-LR (MC-LR) a cyclic toxin produced by cyanobacterial species is known to exert detrimental effects on various organs, including lung. Several investigators demonstrated that MC-LR exerts pulmonary toxicity, but the underlying mechanisms remain unclear. This study aimed to investigate whether exposure to MC-LR-induced lung inflammation and examine the underlying mechanisms. Thirty specific pathogen-free (SPF) male mice were allocated into control and MC-LR treatment groups. Mice were intraperitoneally injected with physiological saline or MC-LR (20 μg/kg) daily for a total of 21 days. Our findings indicated that exposure to MC-LR-produced histopathological changes in lung tissue, including thickening of alveolar walls and inflammatory infiltration. MC-LR was found to upregulate mRNA expression levels of pro-inflammatory cytokines TNFα, IL-6, IL-1β, and IL-18. Further, MC-LR significantly elevated the expression levels of proteins associated with the NF-κB/NLRP3 pathway p-NF-κB, NLRP3, Caspase-1, ASC. The activation of NF-κB/NLRP3 pathway further promoted the release of inflammatory cytokine IL-1β and cleavage of pyroptosis-associated GSDMD protein. These findings indicate that MC-LR may induce lung inflammation by promoting cell pyroptosis via the activation of the NF-κB/NLRP3 pathway.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"385-394"},"PeriodicalIF":2.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958998","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}
Yaqi Wang, Yue Yang, Mei Yuan, Fei Yang, Wen Zeng, Jun Liu, Chunhua Zhan
{"title":"MC-LR induced apoptosis in human embryonic kidney (HEK293) cells through activation of TNF-R1/RIPK1 pathway.","authors":"Yaqi Wang, Yue Yang, Mei Yuan, Fei Yang, Wen Zeng, Jun Liu, Chunhua Zhan","doi":"10.1080/15287394.2024.2439532","DOIUrl":"10.1080/15287394.2024.2439532","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"339-348"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866474","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":"Effect of 2,5-hexanedione on rat ovarian granulosa cell apoptosis involves endoplasmic reticulum stress-dependent m-TOR signaling pathway.","authors":"Lemei Zhu, Yue Yang, Jingsi Tan, Yibo Lin, Jiaqi Qing, Xin Li, Lingfeng Zeng","doi":"10.1080/15287394.2024.2438832","DOIUrl":"10.1080/15287394.2024.2438832","url":null,"abstract":"<p><p>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, Ca<sup>2+</sup> 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 <i>Bax</i> and <i>Caspase 3</i>, (2) decreased expression levels of the anti-apoptosis gene <i>Bcl-2</i>, 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.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"319-328"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820327","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}
Rong Zhang, Lili Yang, Sihong Long, Shengyu Zhang, Jia Wei, Fei Yang
{"title":"Isolation and identification of a native bacterium <i>Citrobacter farmeri</i> against microcystin-LR in anaerobic environments.","authors":"Rong Zhang, Lili Yang, Sihong Long, Shengyu Zhang, Jia Wei, Fei Yang","doi":"10.1080/15287394.2024.2438837","DOIUrl":"10.1080/15287394.2024.2438837","url":null,"abstract":"<p><p>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 <i>Citrobacter farmeri</i> (<i>C. farmeri</i>). 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 <i>C. farmeri</i> A4 did not possess the known MC-degrading gene <i>mlrABCD</i>, suggesting the involvement of an <i>mlrABCD</i>-independent anaerobic degradation pathway. Data demonstrated that the bacterial strain <i>C. farmeri</i> 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.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":"88 8","pages":"329-338"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442777","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":"Association of ambient particulate matter (PM<sub>2.5</sub>) with reduced sex ratio at birth after the implementation of a rapid transit system in Taipei, Taiwan.","authors":"Shang-Shyue Tsai, Yi-Hao Weng, Chun-Yuh Yang","doi":"10.1080/15287394.2024.2436992","DOIUrl":"10.1080/15287394.2024.2436992","url":null,"abstract":"<p><p>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<sub>2.5</sub>) 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<sub>2.5</sub> 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<sub>2.5</sub> 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.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"310-317"},"PeriodicalIF":2.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781854","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}
Raquel Stefanello, Raissa Tainá Puntel, Daiane Balconi Bevilaqua, Wagner Jesus da Silva Garcia, Cristiano Rodrigo Bohn Rhoden, Lucio Strazzabosco Dorneles
{"title":"Conditioning rice seeds with chitosan to mitigate salt stress.","authors":"Raquel Stefanello, Raissa Tainá Puntel, Daiane Balconi Bevilaqua, Wagner Jesus da Silva Garcia, Cristiano Rodrigo Bohn Rhoden, Lucio Strazzabosco Dorneles","doi":"10.1080/15287394.2024.2434656","DOIUrl":"10.1080/15287394.2024.2434656","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"279-290"},"PeriodicalIF":2.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883626","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}
Yiwen Hou, Ying Liu, Yue Yang, Shuaishuai Xu, Fei Yang
{"title":"Exposure to MC-LR activates the RAF/ERK signaling pathway, leading to renal inflammation and tissue damage in mice.","authors":"Yiwen Hou, Ying Liu, Yue Yang, Shuaishuai Xu, Fei Yang","doi":"10.1080/15287394.2024.2435632","DOIUrl":"10.1080/15287394.2024.2435632","url":null,"abstract":"<p><p>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 <i>in vitro</i> and male C57BL/6 <i>in vivo</i>. In the <i>in vitro</i> 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.</p>","PeriodicalId":54758,"journal":{"name":"Journal of Toxicology and Environmental Health-Part A-Current Issues","volume":" ","pages":"301-309"},"PeriodicalIF":2.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878573","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}