Toxicology and applied pharmacology最新文献_第4页

Protective effect of hydroxysafflor yellow a on thioacetamide-induced liver injury and osteopenia in zebrafish 羟基红花黄色素对硫代乙酰胺诱导的斑马鱼肝损伤和骨质疏松的保护作用

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-09-19 DOI: 10.1016/j.taap.2024.117109

{"title":"Protective effect of hydroxysafflor yellow a on thioacetamide-induced liver injury and osteopenia in zebrafish","authors":"","doi":"10.1016/j.taap.2024.117109","DOIUrl":"10.1016/j.taap.2024.117109","url":null,"abstract":"<div><div>Hydroxysafflor yellow A (HSYA) is the main water-soluble compound of safflower. It is commonly used in liver disease treatment and has anti-osteoporotic activity. However, the specific mechanism of HSYA is not yet fully understood. Thioacetamide (TAA) has toxic effects on the liver and is widely used in establishing animal models of cirrhosis and liver fibrosis. In research of liver-related diseases and bone deformation in vivo, the zebrafish has become a frequently utilized animal model. In establishing a TAA-induced zebrafish liver injury model, we found that TAA-induced zebrafish also developed osteopenia. The aim of our study is to investigate the protective effect of HSYA on TAA-induced liver injury and osteopenia in zebrafish. The findings demonstrated that HSYA alleviated hepatic oxidative stress, inhibited the release of inflammatory factors, and promoted in vivo skeletal mineralization in zebrafish larvae. Further Real-time Polymerase Chain Reaction and Western blotting analyses showed that HSYA altered the expression levels of SIRT1, HMGB1, TLR4, MYD88 and NF-ΚB, ameliorated TAA-induced liver injury, reduced the release of inflammation-related factors IL-6, IL-1β, TNF-α, regulated the ratio of RANKL/OPG, ameliorated TAA-induced osteopenia. In conclusion, our study demonstrated that HSYA exhibited a noteworthy beneficial influence on TAA-induced liver injury and osteopenia in zebrafish, this finding provide a foundation for the application of HSYA in clinical research.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The downregulation of TREM2 exacerbates toxicity of development and neurobehavior induced by aluminum chloride and nano-alumina in adult zebrafish TREM2 的下调会加剧氯化铝和纳米氧化铝对成年斑马鱼发育和神经行为的毒性。

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-09-15 DOI: 10.1016/j.taap.2024.117107

{"title":"The downregulation of TREM2 exacerbates toxicity of development and neurobehavior induced by aluminum chloride and nano-alumina in adult zebrafish","authors":"","doi":"10.1016/j.taap.2024.117107","DOIUrl":"10.1016/j.taap.2024.117107","url":null,"abstract":"<div><p>To investigate the difference in the development and neurobehavior between aluminum chloride (AlCl<sub>3</sub>) and nano-alumina (AlNPs) in adult zebrafish and the role of triggering receptor expressed on myeloid cells (TREM2) in this process. Zebrafish embryos were randomly administered with control, negative control, TREM2 knockdown, AlCl<sub>3</sub>, TREM2 knockdown + AlCl<sub>3</sub>, AlNPs, and TREM2 knockdown + AlNPs, wherein AlCl<sub>3</sub> and AlNPs were 50 mg/L and TREM2 knockdown was achieved by microinjecting lentiviral-containing TREM2 inhibitors into the yolk sac. We assessed development, neurobehavior, histopathology, ultrastructural structure, neurotransmitters (AChE, DA), SOD, genes of TREM2 and neurodevelopment (α1-tubulin, syn2a, mbp), and AD-related proteins and genes. AlCl<sub>3</sub> significantly lowered the malformation rate than AlNPs, and further increased rates of malformation and mortality following TREM2 knockdown. The locomotor ability, learning and memory were similar between AlCl<sub>3</sub> and AlNPs. TREM2 deficiency further exacerbated their impairment in panic reflex, microglia decrease, and nerve fibers thickening and tangling. AlCl<sub>3</sub>, rather than AlNPs, significantly elevated AChE activity and p-tau content while decreasing TREM2 and syn2a levels than the control. TREM2 loss further aggravated impairment in the AChE and SOD activity, and psen1 and p-tau levels. Therefore, AlCl<sub>3</sub> induces greater developmental toxicity but equivalent neurobehavior toxicity than AlNPs, while their toxicity was intensified by TREM2 deficiency.</p></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Azoospermia and multi-organ damage in juvenile rats exposed to α-Terpineol from weaning to sexual maturity 从断奶到性成熟期间暴露于 α-松油醇的幼鼠的无精子症和多器官损伤

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-09-13 DOI: 10.1016/j.taap.2024.117106

{"title":"Azoospermia and multi-organ damage in juvenile rats exposed to α-Terpineol from weaning to sexual maturity","authors":"","doi":"10.1016/j.taap.2024.117106","DOIUrl":"10.1016/j.taap.2024.117106","url":null,"abstract":"<div><p>This study aimed to evaluate the repeated oral administration of α-terpineol in juvenile Wistar rats over a 70-day period. The objective was to assess the potential systemic and reproductive toxicity of α-terpineol when administered by gavage at doses of 75, 150, and 300 mg/kg/day to juvenile Wistar rats for 70 days from postnatal day 24. The control group received corn oil for 70 days. During the study, various parameters were evaluated, including clinical signs, body weight, food intake, neurobehavioral observations, haematology, serum biochemistry, organ weights, steroidogenic gene expression, and histopathological examination. No toxicity-related changes were observed in body weight, food intake, neurobehavioral observations, or steroidogenic gene expression. However, sperm evaluation revealed a complete absence of sperm and delayed sexual maturation. Total cholesterol was significantly elevated in both sexes, and serum testosterone was reduced at the 150 and 300 mg/kg doses. Microscopic examination showed severe pathological changes in the testes, epididymis, liver, and kidneys of both males and females. After the 14-day recovery period, total cholesterol levels returned to the normal range, but no recovery was observed in the other organs. The no-observed-adverse-effect level was 75 mg/kg/day for male rats based on the histopathological findings in the testes, liver, and kidneys, and for female rats based on the kidney and liver histopathology.</p></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Wogonin induces mitochondrial apoptosis and synergizes with venetoclax in diffuse large B-cell lymphoma Wogonin 可诱导弥漫大 B 细胞淋巴瘤线粒体凋亡并与 Venetoclax 协同作用

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-09-13 DOI: 10.1016/j.taap.2024.117103

{"title":"Wogonin induces mitochondrial apoptosis and synergizes with venetoclax in diffuse large B-cell lymphoma","authors":"","doi":"10.1016/j.taap.2024.117103","DOIUrl":"10.1016/j.taap.2024.117103","url":null,"abstract":"<div><p>Diffuse large B-cell lymphoma (DLBCL) is among the most aggressive hematological malignancies and patients are commonly treated with combinatorial immunochemotherapies such as R-CHOP. Till now, the prognoses are still variable and unsatisfactory, depending on the molecular subtype and the treatment response. Developing effective and tolerable new agents is always urgently needed, and compounds from a natural source have gained increasing attentions. Wogonin is an active flavonoid extracted from the traditional Chinese herbal medicine <em>Scutellaria baicalensis</em> Georgi and has shown extensive antitumor potentials. However, the therapeutic effect of wogonin on DLBCL remains unknown. Here, we found that treatment with wogonin dose- and time-dependently reduced the viability in a panel of established DLBCL cell lines. The cytotoxicity of wogonin was mediated through apoptosis induction, along with the loss of mitochondrial membrane potential and the downregulation of BCL-2, MCL-1, and BCL-xL. In terms of the mechanism, wogonin inhibited the PI3K and MAPK pathways, as evidenced by the clear decline in the phosphorylation of AKT, GSK3β, S6, ERK, and P38. Furthermore, the combination of wogonin and the BCL-2 inhibitor venetoclax elicited synergistically enhanced killing effect on DLBCL cells regardless of their molecular subtypes. Finally, administration of wogonin significantly impeded the progression of the DLBCL tumor in a xenograft animal model without obvious side effects. Taken together, the present study suggests a promising potential of wogonin in the treatment of DLBCL patients either as monotherapy or an adjuvant for venetoclax-based combinations.</p></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From computational prediction to experimental validation: Hesperidin's anti-Urolithiatic activity in sodium oxalate-induced urolithiasis models in fruit flies and mice 从计算预测到实验验证：橙皮甙在草酸钠诱导的果蝇和小鼠尿石症模型中的抗尿石症活性

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-09-12 DOI: 10.1016/j.taap.2024.117104

{"title":"From computational prediction to experimental validation: Hesperidin's anti-Urolithiatic activity in sodium oxalate-induced urolithiasis models in fruit flies and mice","authors":"","doi":"10.1016/j.taap.2024.117104","DOIUrl":"10.1016/j.taap.2024.117104","url":null,"abstract":"<div><p>Kidney stones have been a long-standing health issue, contributing to renal failure, especially in co-morbid patients. There is an increasing interest in exploring natural compounds with anti-urolithiatic properties. Our study utilized <em>in-silico</em> techniques followed by <em>in vivo</em> experiments to evaluate the anti-urolithiatic potential of selected phytoconstituents. Molecular docking studies were conducted on 11 different targets, including inhibitors of kidney stone formation, antioxidant enzymes, and biomarkers of kidney injury, to explore the potential of anti-urolithiatic effects of 38 phytoconstituents from medicinal plants possessing diuretic activity. Further, the anti-urolithiatic activity of the phytoconstituent was evaluated using a sodium oxalate-induced urolithiatic fruit fly and mouse model. Hesperidin emerged as a promising candidate, exhibiting binding interactions with a specific set of 11 target proteins involved in crystal formation with minimal free energy. Hesperidin demonstrated promising anti-urolithiatic potential in mitigating urolithiasis as evidenced by reduced crystal covered area of Malpighian tubules of fruit fly and reduced blood urea nitrogen (BUN), serum creatinine and serum sodium, potassium levels in mice. Moreover, it increased urine volume, preventing crystal deposition, and reduced urine urea nitrogen, creatinine, sodium, and potassium levels, enhancing urine flow and preventing crystal accumulation. Histopathological analysis further supported its efficacy by showing minimal crystal deposition and reduced kidney damage. Hesperidin exhibited superior effectiveness in reducing various serum and urine parameters, making it promising alternatives for urolithiasis management warranting further investigation to determine its safety and optimal dosages in human.</p></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to "Effects of a spiroketal compound Peniciketal A and its molecular mechanisms on growth inhibition in human leukemia" [Toxicology and Applied Pharmacology, 2019, 1:366:1-9]. 对 "一种螺酮化合物Peniciketal A及其分子机制对人类白血病生长抑制的影响 "的更正[《毒理学与应用药理学》，2019，1:366:1-9]。

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-09-12 DOI: 10.1016/j.taap.2024.117105

Xue Gao, Yuming Zhou, Hongliu Sun, Desheng Liu, Jing Zhang, Junru Zhang, Weizhong Liu, Xiaohong Pan

引用次数: 0

Hydramethylnon induces mitochondria-mediated apoptosis in BEAS-2B human bronchial epithelial cells 氟蚁腙可诱导 BEAS-2B 人支气管上皮细胞中线粒体介导的细胞凋亡。

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-09-11 DOI: 10.1016/j.taap.2024.117102

{"title":"Hydramethylnon induces mitochondria-mediated apoptosis in BEAS-2B human bronchial epithelial cells","authors":"","doi":"10.1016/j.taap.2024.117102","DOIUrl":"10.1016/j.taap.2024.117102","url":null,"abstract":"<div><p>Typically used household chemicals comprise numerous compounds. Determining mixture toxicity, as observed when using household chemicals containing multiple substances, is of considerable importance from a regulatory perspective. Upon examining the toxic effects of household chemical mixtures, we observed that hydramethylnon combined with tetramethrin resulted in synergistic toxicity. To determine the unknown toxicity mechanism of hydramethylnon, which carries the risk of inhalation exposure when using household chemicals, we conducted a further investigation using BEAS-2B cells, a human bronchial epithelial cell line. Hydramethylnon-induced cytotoxicity was determined following 24 and 48 h of exposure using the water-soluble tetrazolium 1 and lactate dehydrogenase assays. To elucidate the toxicity mechanism, we utilized flow cytometry and measured the levels of apoptosis-related proteins and caspase activities. Given that hydramethylnon, as an insecticide, disrupts the mitochondrial electron transfer chain, we analyzed the relevant mechanisms, including mitochondrial superoxide levels as well as the mitochondrial membrane potential (MMP). Hydramethylnon dose-dependently induced BEAS-2B cell apoptosis via the intrinsic pathway. Furthermore, it significantly increased mitochondrial superoxide levels and disrupted the MMP. Pre-treatment with a caspase inhibitor (<em>Z</em>-DEVD-FMK) confirmed that hydramethylnon induced caspase-dependent apoptosis. Apoptosis, a key event in the toxicological process of chemicals, can lead to lung diseases, including fibrosis and cancer. The results of the present study suggest a mechanism of toxicity of hydramethrylnon, an organofluorine biocide whose toxicity has been little studied, to the lung epithelium. Considering the potential risks associated with inhalation exposure, these results highlight the need for careful management and regulation of hydramethylnon.</p></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ferulic acid ameliorates concanavalin A-induced hepatic fibrosis in mice via suppressing TGF-β/smad signaling 阿魏酸通过抑制 TGF-β/smad 信号转导，改善金刚烷胺 A 诱导的小鼠肝纤维化

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-09-10 DOI: 10.1016/j.taap.2024.117099

{"title":"Ferulic acid ameliorates concanavalin A-induced hepatic fibrosis in mice via suppressing TGF-β/smad signaling","authors":"","doi":"10.1016/j.taap.2024.117099","DOIUrl":"10.1016/j.taap.2024.117099","url":null,"abstract":"<div><h3>Background and aim</h3><p>Hepatic fibrosis, one of the main reasons for death globally, is a serious complication of chronic liver disorders. However, the available therapies for liver fibrosis are limited, ineffective, and often associated with adverse events. Hence, seeking for a novel, effective therapy is warranted. Our objective was to investigate the potential efficacy of ferulic acid (FA), a phenolic phytochemical, at different doses in hindering the progress of concanavalin A (Con A)-induced hepatic fibrosis and explore the involved mechanisms.</p></div><div><h3>Methods</h3><p>Thirty-six mice were assorted into 6 groups (<em>n</em> = 6): Group I (control); group II received FA (20 mg/kg/day orally for 4 weeks); group III received Con A (6 mg/kg/week/i.v.) for 4 weeks; groups IV, V, and VI received Con A and were offered FA at 5, 10, and 20 mg/kg/day, respectively.</p></div><div><h3>Results</h3><p>The data showed the palliative effect of FA against Con A-induced fibrosis in a dose-dependent manner. This was obvious from the recovery of liver markers and hepatic architecture with the regression of fibrosis in FA-treated mice. FA abolished Con A-mediated oxidative insults and promoted the antioxidant enzyme activities, which run through the Nrf2/HO-1 signaling. Additionally, FA suppressed Con A-induced increase in NF-kB and IL-β levels, and TNF-α immune-expression. The anti-fibrotic effect of FA was evident from the drop in TGF-β, smad3 levels, α-SMA expression, and hydroxyproline content.</p></div><div><h3>Conclusion</h3><p>FA attenuated Con A-induced liver fibrosis through stimulating Nrf2 signaling, suppressing NF-kB, and inhibiting the TGF-β/smad3 signaling pathway. Thus FA can be considered as a promising therapy for combating liver fibrosis.</p></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Asiatic acid induces lung cancer toxicity by triggering SRC-mediated ferroptosis 积雪草酸通过诱导 SRC 介导的铁变态反应诱导肺癌毒性

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-09-07 DOI: 10.1016/j.taap.2024.117097

{"title":"Asiatic acid induces lung cancer toxicity by triggering SRC-mediated ferroptosis","authors":"","doi":"10.1016/j.taap.2024.117097","DOIUrl":"10.1016/j.taap.2024.117097","url":null,"abstract":"<div><p>Ferroptosis is a recently discovered form of regulated cell death that shows promise as a novel approach for inducing tumor cell death in cancer treatment, with significant research potential. Asiatic acid (AA), a key component of the traditional Chinese medicine <em>Centella asiatica</em>, has been identified as having potential therapeutic benefits for various diseases, particularly cancer. Non-small cell lung cancer (NSCLC) is a challenging and prevalent form of cancer to treat. In our study, we utilized network pharmacology, molecular docking, and experimental methods to investigate the potential of AA in treating NSCLC and to elucidate its role in inhibiting cancer through the ferroptosis pathway. Through network pharmacology analysis, we identified that AA targets the core NSCLC protein SRC through the ferroptosis pathway. Our experiments demonstrated that treatment with AA led to increased iron accumulation, mitochondrial membrane potential, and expression of ferroptosis markers glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and acyl-CoA synthetase long chain family member 4 (ACSL4) in NSCLC cells, confirming the induction of ferroptosis. In conclusion, AA has the potential to target SRC and induce NSCLC cell death through the ferroptosis pathway, offering a promising approach for cancer treatment.</p></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0041008X24002953/pdfft?md5=9f07fe8f5848ba70843421f46d6ec8e7&pid=1-s2.0-S0041008X24002953-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

1,2,4-trihydroxybenzene induces non-apoptotic cell death via the structural damage of intracellular organelles 1,2,4-三羟基苯通过细胞内细胞器的结构损伤诱导细胞非凋亡。

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-09-07 DOI: 10.1016/j.taap.2024.117096

{"title":"1,2,4-trihydroxybenzene induces non-apoptotic cell death via the structural damage of intracellular organelles","authors":"","doi":"10.1016/j.taap.2024.117096","DOIUrl":"10.1016/j.taap.2024.117096","url":null,"abstract":"<div><p>Benzene occurs naturally and is widely applied in the production process of petrochemical products. It is mainly exposed through the respiratory tract and dermal and metabolized in the liver, leading to systemic health effects, and 1,2,4-trihydroxybenzene (THB) is a benzene metabolite used as a hair dye ingredient in some countries. In an effort to identify a toxic mechanism of THB, we first analyzed the hair of consumers who used a shampoo containing THB, and contrary to our expectations, THB was not persistent in the hair. Following, we treated THB to human keratinocytes and HeLa Chang liver cells. Membrane damage was observed in both cell lines, which was more notable in HeLa Chang liver cells than in keratinocytes. Thus, we decided on HeLa Chang liver cells as target cells for further study. Cell viability decreased sharply between 20 μg/ml and 40 μg/mL, inducing G2/M phase arrest and non-apoptotic cell death. The expression of carcinogenesis-, DNA damage-, and transcriptional dysregulation–related genes were notably up-regulated, and the structure and function of mitochondria were disrupted. The volume of the ER and acidic compartments decreased, and intracellular ROS and calcium ion levels increased. More interestingly, we found that THB formed unique structures within the cells, especially around the nuclear membrane, and that those structures seemed to dig into the nucleus over time. A reverse docking analysis also showed that SULT1A1, CYP2E1, and CAT, known to play a significant role in protecting cells from harmful factors, might be potential target proteins for THB. Taken together, we suggest that THB induces non-apoptotic cell death via structural damage of intracellular organelles, especially the nuclear membrane.</p></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142155002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0