Toxicology and applied pharmacology最新文献_第10页

New insights into the mechanisms underlying 5-hydroxymethylfurfural-induced suppression of testosterone biosynthesis in vivo and in vitro 5-hydroxymethylfurfural 诱导的体内和体外睾酮生物合成抑制机制的新见解。

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-11-06 DOI: 10.1016/j.taap.2024.117142

Banu Orta Yilmaz, Yasemin Aydin

{"title":"New insights into the mechanisms underlying 5-hydroxymethylfurfural-induced suppression of testosterone biosynthesis in vivo and in vitro","authors":"Banu Orta Yilmaz, Yasemin Aydin","doi":"10.1016/j.taap.2024.117142","DOIUrl":"10.1016/j.taap.2024.117142","url":null,"abstract":"<div><div>5-hydroxymethylfurfural (HMF), produced by the Maillard reaction, can indicate thermal processes in food. Previous research has examined the cytotoxic, genotoxic, mutagenic, and carcinogenic characteristics of HMF and its derivatives in different organs. Nevertheless, there is currently no available evidence about the impact of HMF on male reproductive toxicity. In this study, the effects of HMF on testosterone biosynthesis in both mouse testis and TM3 Leydig cells were investigated. HMF was administered to mice at doses of 30 and 300 mg/kg/day for 21 days and to Leydig cells at concentrations of 0.1, 1, and 10 mM for 24 h. The mechanism of action of HMF on testosterone biosynthesis in both mouse testis and Leydig cells was revealed by measuring the amount of testosterone, 3′,5′-cyclic adenosine monophosphate (cAMP) levels, and the expression level of some important genes in the steroidogenic pathway. In addition, its effects on general testis were examined through histopathological evaluations. Upon examination of the results, it was observed that HMF had a significant impact on reducing testosterone and cAMP levels. Furthermore, HMF inhibited the expression of steroidogenic genes, including steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme, 3β-hydroxy dehydrogenase, and 17β-hydroxy dehydrogenase, as well as transcription factors, such as steroidogenic factor-1, GATA binding protein-4, and nerve growth factor IB. HMF-administrated groups had germinal epithelium degradation, vacuolization, and disorders in the interstitial area. Consequently, it has been proven for the first time that HMF can damage the male reproductive system by detrimentally impacting the production of testosterone.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"493 ","pages":"Article 117142"},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628751","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

Sildenafil citrate induces prostatic hyperplasia in BPH model rats and aged rats 枸橼酸西地那非可诱导良性前列腺增生模型大鼠和老年大鼠的前列腺增生。

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-11-05 DOI: 10.1016/j.taap.2024.117147

Sisi Huang , Dongyan Huang , Xin Su , Rongfu Yang , Congcong Shao , Juan Jiang , Jun Li , Jianhui Wu

{"title":"Sildenafil citrate induces prostatic hyperplasia in BPH model rats and aged rats","authors":"Sisi Huang , Dongyan Huang , Xin Su , Rongfu Yang , Congcong Shao , Juan Jiang , Jun Li , Jianhui Wu","doi":"10.1016/j.taap.2024.117147","DOIUrl":"10.1016/j.taap.2024.117147","url":null,"abstract":"<div><div>Erectile dysfunction (ED), a prevalent disease among middle-aged and elderly males, significantly impacts both patient and partner quality of life. Phosphodiesterase type 5 inhibitor (PDE5i) represents an effective therapeutic method for ED. Given their widespread global utilization, concerns arise regarding potential reproduction-related problems arising from clinical use. During the extensive development of PDE5i, we speculated that the potential of these inhibitors to variably induce prostatic hyperplasia, but this field remains unexplored. In order to verify the male reproductive toxicity of PDE5i, sildenafil citrate at doses of 5, 10 and 20 mg/kg was administered in BPH model rats and aged rats. Anatomical and pathological analyses indicate a compelling association between sildenafil citrate administration and the promotion of prostatic hyperplasia in both BPH model rats and aged rats. Serum analysis showed that serum prostate-binding protein (PBP) exhibited a non-significant but increasing trend following administration of sildenafil citrate to BPH model rats. Furthermore, significant increase in serum levels of E2 and T, as well as T in dorsal lobe prostate tissue of aged rats, were observed compared to the model control group. These results confirm the hypothesis that sildenafil citrate has reproductive toxicity in males.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"493 ","pages":"Article 117147"},"PeriodicalIF":3.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591362","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

Valifenalate-induced non-adverse thyroid changes via adaptive induction of uridine 5′-diphospho-glucuronosyltransferase (UGT) in the liver of dogs and rats but not humans 戊烯二酸通过适应性诱导狗和大鼠肝脏中的尿苷-5'-二磷酸-葡萄糖醛酸转移酶（UGT）诱导甲状腺的非不良变化，而不是人类。

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-11-03 DOI: 10.1016/j.taap.2024.117143

Christine Walter , Audrey Baze , Claire Grant , Lysiane Richert , Werner Bomann

{"title":"Valifenalate-induced non-adverse thyroid changes via adaptive induction of uridine 5′-diphospho-glucuronosyltransferase (UGT) in the liver of dogs and rats but not humans","authors":"Christine Walter , Audrey Baze , Claire Grant , Lysiane Richert , Werner Bomann","doi":"10.1016/j.taap.2024.117143","DOIUrl":"10.1016/j.taap.2024.117143","url":null,"abstract":"<div><div>Some rat and dog toxicology studies with the fungicide valifenalate showed minimal, non-adverse thyroid changes, mostly above the maximum tolerated dose, and concomitantly with liver effects. This publication describes their mode of action (MOA), combining <em>in vivo</em> and new approach methodologies (NAMs), in a weight of evidence approach.</div><div>Data demonstrate a MOA of liver enzyme induction <em>via</em> nuclear receptor CAR/PXR activation, increased thyroxine (T4) metabolism and elevated thyroid stimulating hormone (TSH) level, leading to thyroid follicular cell hypertrophy and increased thyroid weight. Non-human relevance of the MOA was demonstrated in <em>in vitro</em> cross species assays in rat, dog and human hepatocytes. Increased gene expression and activity of cytochrome P450s (CYPs) and uridine 5′-diphospho-glucuronosyltransferases (UGTs) were observed in rat and dog hepatocytes exposed to valifenalate, with increased T4 clearance and/or T4 glucuronidation/T4-UGT activity. Therefore, a causal relationship between increased liver enzyme induction and thyroid effects in dogs and rats is concluded. Rat hepatocytes were most sensitive, while valifenalate did not increase T4-UGT activity above 2-fold of vehicle control or T4 glucuronidation and T4 clearance in human hepatocytes. Consequently, valifenalate exposure in humans is unlikely to lead to decreased T4 levels, and subsequent thyroid and developmental neurotoxicity effects. Alternative human-relevant thyroid MOAs were excluded, <em>i.e.</em> inhibition of deiodinases (DIO), thyroperoxidase (TPO) or the sodium iodide symporter (NIS).</div><div>Due to known species differences in thyroid homeostasis between humans and laboratory animals and, importantly, based on the presented data, this liver enzyme mediated MOA is considered not relevant for human hazard assessment.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"494 ","pages":"Article 117143"},"PeriodicalIF":3.3,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584314","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

Exploring the potential use of Caenorhabditis elegans as an animal model for evaluating chemical-induced intestinal dysfunction 探索将草履虫作为动物模型用于评估化学物质引起的肠道功能障碍的可能性。

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-11-03 DOI: 10.1016/j.taap.2024.117140

Xiao-Pan Zhang , Xuan Ma , Jun-Ling Liu , Ai-Lin Liu

{"title":"Exploring the potential use of Caenorhabditis elegans as an animal model for evaluating chemical-induced intestinal dysfunction","authors":"Xiao-Pan Zhang , Xuan Ma , Jun-Ling Liu , Ai-Lin Liu","doi":"10.1016/j.taap.2024.117140","DOIUrl":"10.1016/j.taap.2024.117140","url":null,"abstract":"<div><div>Evaluating intestinal toxicity is crucial for identifying and preventing the harmful effects of environmental chemicals. Owing to the limitations of existing models in evaluating intestinal toxicity, the development of alternative models is urgently needed. This study explored the potential use of the nematode <em>Caenorhabditis elegans</em> as a model animal for assessing chemical-induced intestinal dysfunction. Changes in intestinal permeability and nutrient absorption in <em>C. elegans</em> individuals exposed to four intestine-disrupting chemicals (sodium dodecyl sulfate (SDS), dextran sulfate sodium (DSS), lipopolysaccharide (LPS) and ethanol) were examined using dye stain assays, an enzymatic photometric assay, and fluorescent probe uptake assays. Additionally, epigallocatechin-3-gallate (EGCG), an intestine-protecting phytochemical, was chosen to prevent ethanol-induced intestinal damage. The results indicated that SDS, DSS, LPS, and ethanol compromised the intestinal barrier in <em>C. elegans</em>. SDS had no effect on glucose absorption, but LPS, DSS, and ethanol inhibited or tended to inhibit glucose absorption. SDS, DSS, LPS, and ethanol reduced fatty acid absorption. LPS increased peptide absorption at a low dose but decreased it at a high dose; SDS, DSS, and ethanol attenuated peptide absorption. EGCG protected against the disruption of the intestinal barrier that was induced by ethanol treatment. These results suggest that <em>C. elegans</em> is a suitable surrogate model animal for evaluating chemical-induced intestinal dysfunction. These findings also provide new insights into the effects of SDS, DSS, LPS, and ethanol on intestinal function and highlight the potential of EGCG as a natural dietary intervention to protect individuals who use excess alcohol from intestinal injury.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"493 ","pages":"Article 117140"},"PeriodicalIF":3.3,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584312","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

Cepharanthine inhibits the proliferation of glioblastoma cells by blocking the autophagy–lysosomal pathway 头孢噻啶通过阻断自噬-溶酶体途径抑制胶质母细胞瘤细胞的增殖。

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-11-03 DOI: 10.1016/j.taap.2024.117141

Xiangjun Dong , Weiyi Zhu , Nianrong Wang

{"title":"Cepharanthine inhibits the proliferation of glioblastoma cells by blocking the autophagy–lysosomal pathway","authors":"Xiangjun Dong , Weiyi Zhu , Nianrong Wang","doi":"10.1016/j.taap.2024.117141","DOIUrl":"10.1016/j.taap.2024.117141","url":null,"abstract":"<div><div>Cepharanthine (CEP) is a <em>Stephania cepharantha-</em>derived bioactive alkaloid that can inhibit the progression of numerous tumors. However, the effects and specific mechanisms of CEP performance in glioblastoma (GBM) remain unclear. Thus, this study focused on exploring the effects of CEP on GBM and clarifying the underlying mechanisms. U251 and U87 cells were selected to estimate the anti-GBM effects of CEP, and the possible targets of CEP were analyzed using RNA sequencing (RNA-seq). Validation experiments based on RNA-seq data were performed to clarify the key pathway by which CEP mediates GBM cells response. Results showed that CEP administration successfully inhibited the proliferation and induced the cell cycle arrest and apoptosis of the GBM cells. RNA-seq analysis after CEP administration identified 386 differentially expressed genes, which were highly enriched in the autophagy–lysosomal pathway. Subsequent findings demonstrated that CEP exhibited the potential to curb GBM progression by causing lysosomal and autophagic dysfunction. Taken together, our results indicate that CEP is a potential drug candidate for GBM intervention.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"493 ","pages":"Article 117141"},"PeriodicalIF":3.3,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584298","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

On the relationship between hERG inhibition and the magnitude of QTc prolongation: An in vitro to clinical translational analysis hERG 抑制与 QTc 延长程度之间的关系：从体外到临床的转化分析

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-11-01 DOI: 10.1016/j.taap.2024.117135

Alexander R. Harmer , Michael G. Rolf

{"title":"On the relationship between hERG inhibition and the magnitude of QTc prolongation: An in vitro to clinical translational analysis","authors":"Alexander R. Harmer , Michael G. Rolf","doi":"10.1016/j.taap.2024.117135","DOIUrl":"10.1016/j.taap.2024.117135","url":null,"abstract":"<div><div>Assessing the magnitude of QTc prolongation is crucial in drug development due to its association with Torsades de Pointes. Inhibition of the hERG channel, pivotal in cardiac repolarization, is a key factor in evaluating this risk. In this study, the relationship between hERG inhibition and QTc prolongation magnitude was investigated, with the aim to derive simple guidance on the required hERG margin to avoid a large (>20 ms) QTc prolongation.</div></div><div><h3>Methods</h3><div>Data from literature and FDA sources were searched for compounds with hERG IC<sub>50</sub> values alongside clinical QTc data with paired plasma concentrations, or compounds demonstrating a clinical concentration-QTc relationship. Relationships between hERG inhibition, hERG IC<sub>50</sub> margin to unbound plasma C<sub>max</sub>, and QTc prolongation magnitude were calculated.</div></div><div><h3>Results</h3><div>Analysis of 148 clinical QTc observations from 98 compounds revealed that compounds associated with QTc prolongation >10 ms typically exhibited hERG margins of ≤33-fold, while those exceeding 20 ms were generally associated with margins of ≤24-fold. QTc increases above 10 ms were not observed at hERG margins >100-fold. Based on 53 clinical concentration-QTc datasets, modest hERG inhibition levels of <strong>∼</strong>4–6 % correlated with a 10 ms QTc prolongation, while <strong>∼</strong>10–13 % inhibition corresponded to a 20 ms prolongation.</div></div><div><h3>Conclusions</h3><div>This study enhances understanding of the relationship between hERG inhibition and QTc prolongation magnitude, by conducting analysis across a wide range of 98 compounds. This information can be used to determine the optimal hERG margin, particularly for drug discovery projects with limited scope to completely design-out hERG activity.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"492 ","pages":"Article 117135"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561202","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

Lonicerin protects pancreatic acinar cells from caerulein-induced apoptosis, inflammation, and ferroptosis by activating the SIRT1/GPX4 signaling pathway 忍冬藤素通过激活SIRT1/GPX4信号通路，保护胰腺尖叶细胞免受caerulein诱导的凋亡、炎症和铁中毒的影响。

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-11-01 DOI: 10.1016/j.taap.2024.117136

Dahuan Li , Chunyan Li , Simin Jiang , Tianzhong Wang , Chong Zhang , Zhao Zhu , Guoxiu Zhang , Bangjiang Fang

{"title":"Lonicerin protects pancreatic acinar cells from caerulein-induced apoptosis, inflammation, and ferroptosis by activating the SIRT1/GPX4 signaling pathway","authors":"Dahuan Li , Chunyan Li , Simin Jiang , Tianzhong Wang , Chong Zhang , Zhao Zhu , Guoxiu Zhang , Bangjiang Fang","doi":"10.1016/j.taap.2024.117136","DOIUrl":"10.1016/j.taap.2024.117136","url":null,"abstract":"<div><div>Acute pancreatitis (AP) is a familiar emergency of digestive system characterized by pancreatic inflammation. Lonicerin (LCR) has been reported to exert anti-inflammatory and immunomodulatory characteristics in several inflammatory diseases. Nevertheless, its role and mechanism involved in AP are still unknown. This study was designed to explore the protective effect and potential mechanism of LCR in AP. In this study, LCR and ferrostatin-1 alleviated, but erastin aggravated caerulein (CAE) exposure-induced cytotoxicity and reduction of cell viability in AR42J cells. LCR exhibited a protective role in CAE-treated AR42J cells, as evidenced by alleviation of apoptosis, inflammation, and ferroptosis. Mechanistically, LCR decreased the phosphorylation level of nuclear factor-kappa B p65 and increased the levels of silent information regulator 1 (SIRT1) and glutathione peroxidase 4 (GPX4) in CAE-treated AR42J cells. Furthermore, functional rescue experiments manifested that knockdown of SIRT1 partially negated the inhibitory action of LCR against CAE-induced apoptosis, inflammation, and ferroptosis in AR42J cells. Overall, LCR mitigates apoptosis, inflammation, and ferroptosis in CAE-exposed AR42J cells, which is related to the activation of the SIRT1/GPX4 signaling pathway.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"492 ","pages":"Article 117136"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547640","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

Hepatotoxicity of N-nitrosodin-propylamine in larval zebrafish by upregulating the Wnt pathway N-nitrosodin-propylamine 通过上调 Wnt 通路对斑马鱼幼体产生肝毒性。

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-11-01 DOI: 10.1016/j.taap.2024.117132

Ying Wang , Shouqiang Huang , Dagang Wang , Jie Wu , Fasheng Liu , Xinjun Liao , Xiaowen Shi , Juhua Xiao , Shouhua Zhang , Huiqiang Lu

{"title":"Hepatotoxicity of N-nitrosodin-propylamine in larval zebrafish by upregulating the Wnt pathway","authors":"Ying Wang , Shouqiang Huang , Dagang Wang , Jie Wu , Fasheng Liu , Xinjun Liao , Xiaowen Shi , Juhua Xiao , Shouhua Zhang , Huiqiang Lu","doi":"10.1016/j.taap.2024.117132","DOIUrl":"10.1016/j.taap.2024.117132","url":null,"abstract":"<div><div>N-nitrosodin-propylamine is an organic compound mainly used in organic synthesis. As a typical pollutant, the accidental release of N-nitrosodin-propylamine may cause environmental pollution, especially water environment pollution. In the present study, we used the zebrafish model for the first time to evaluate the developmental toxicity of this drug in the liver. Zebrafish larvae fertilized at 72hpf showed a range of toxic responses after 72hpf exposure to the drug. These include increased mortality, delayed absorption of yolk sac nutrients, shorter body length, abnormal liver morphology, gene disruption, and altered expression of various indicators with increasing dose. Studies on the mechanism of toxicity showed that N-nitrosodin-propylamine exposure increased the level of oxidative stress, increased the level of apoptosis in hepatocytes, and up-regulated the transcriptional expression level of Wnt signaling pathway genes. Astaxanthin and IWR-1 can effectively save the liver toxicity in zebrafish caused by N-nitrosodin-propylamine. Our study showed that the drug exposure induced hepatotoxicity in zebrafish larvae through the up-regulation of Wnt signaling pathway, oxidative stress and apoptosis.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"492 ","pages":"Article 117132"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558867","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 : 2024-11-01 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

Ferritinophagy is involved in hexavalent chromium-induced ferroptosis in Sertoli cells 铁蛋白吞噬参与了六价铬诱导的 Sertoli 细胞铁突变。

IF 3.3 3区医学

Toxicology and applied pharmacology Pub Date : 2024-11-01 DOI: 10.1016/j.taap.2024.117139

Ruijian Zhuge , Le Zhang , Qian Xue , Rui Wang , Jiayunzhu Xu , Chaofan Wang , Chunyang Meng , Rifeng Lu , Fei Yin , Li Guo

{"title":"Ferritinophagy is involved in hexavalent chromium-induced ferroptosis in Sertoli cells","authors":"Ruijian Zhuge , Le Zhang , Qian Xue , Rui Wang , Jiayunzhu Xu , Chaofan Wang , Chunyang Meng , Rifeng Lu , Fei Yin , Li Guo","doi":"10.1016/j.taap.2024.117139","DOIUrl":"10.1016/j.taap.2024.117139","url":null,"abstract":"<div><div>Hexavalent chromium [Cr(VI)] has significant adverse effects on the environment and human health, particularly on the male reproductive system. Previously, we observed ferroptosis and autophagy in rat testicular injury induced by Cr(VI). In the present study, we focused on the association between ferroptosis and autophagy in mouse Sertoli cells (TM4) exposed to concentrations of 2.5 μМ, 5 μМ, and 10 μМ Cr(VI). Cr(VI) exposure altered mitochondrial ultrastructure; increased intracellular iron, malondialdehyde, and reactive oxygen species (ROS) levels; decreased glutathione content; increased TfR1 protein expression; and decreased GPX4, FPN1, and SLC7A11 protein expression, ultimately resulting in ferroptosis. Additionally, we observed ferritinophagy, increased expression of BECLIN1, LC3B, and NCOA4, and decreased expression of FTH1 and P62. Inhibition of autophagy and ferritinophagy via 3-MA and small interfering RNA (siRNA)-mediated silencing of NCOA4 ameliorated changes in ferritinophagy- and ferroptosis-associated protein expression, and reduced ROS levels. Rats exposed to Cr(VI) exhibited atrophy of testicular seminiferous tubules, a reduction in germ and Sertoli cells, and the occurrence of ferritinophagy and ferroptosis in cells of the rat testes. These results indicate that ferroptosis, triggered by NCOA4-mediated ferritinophagy, is one of the mechanisms that contribute to Cr(VI)-induced damage in Sertoli cells.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"492 ","pages":"Article 117139"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565248","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