Toxicological Research最新文献

{"title":"Maternal smoking and its short- or long-term impact on offspring liver pathologies: a review of experimental and clinical studies.","authors":"Daram Yang, Yu Ji Kim, Jong-Won Kim","doi":"10.1007/s43188-024-00271-y","DOIUrl":"10.1007/s43188-024-00271-y","url":null,"abstract":"<p><p>This review investigates the correlation between prenatal tobacco exposure and the risk of liver diseases in offspring. By synthesizing data from clinical trials and animal studies, it provides a comprehensive overview of the potential mechanisms underlying this association. This review begins by analyzing the prevalence of maternal smoking and its impact on fetal development. It then discusses specific liver diseases observed in offspring exposed prenatally to tobacco, such as acute liver injuries and metabolic dysfunction-associated fatty liver disease, and discusses the underlying pathophysiological pathways. Current evidence indicates that altered fetal liver development, oxidative stress, and genetic modifications may predispose offspring to liver diseases. Furthermore, this review highlights the gaps in current research and the need for longitudinal studies to better understand the long-term effects of prenatal tobacco exposure on the liver. The review concludes with recommendations for public health policies aimed at enhancing our understanding of maternal smoking and mitigating its adverse effects on offspring, emphasizing the importance of smoking cessation during pregnancy.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 2","pages":"123-129"},"PeriodicalIF":1.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516883","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":"Quinine inhibits myogenic differentiation by disrupting AKT signaling pathway.","authors":"Mi Ran Byun, Sou Hyun Kim, RanJu Woo, Seung Jun Noh, Sang Hoon Joo, Young-Suk Jung, Joon-Seok Choi","doi":"10.1007/s43188-024-00273-w","DOIUrl":"10.1007/s43188-024-00273-w","url":null,"abstract":"<p><p>Sarcopenia is a disease characterized by decreased muscle fibers and mass. Although it mainly affects the older adults, it can also occur in various age groups as a secondary effect of medications used for treating certain diseases, such as cancer and diabetes. With population aging, sarcopenia has drawn significant attention owing to its increasing prevalence. However, its pathogenesis remains unclear, and no specific treatment is available. Natural products containing bioactive compounds have long been used as therapeutic agents and are crucial sources for drug development. However, the use of drugs derived from natural extracts is limited because of their ambiguous mechanisms of action and potential side effects. Therefore, a systematic analysis of the potential effects of using natural products is required. In this study, we investigated the effects of the antimalarial drug quinine on myogenic differentiation. Our findings revealed that quinine significantly inhibited the expression of marker genes and proteins associated with myogenic differentiation and markedly impaired muscle regeneration following injury. Furthermore, this reduction occurred when quinine selectively decreased the AKT signaling activity. Quinine reduced muscle protein and gene expression by modulating AKT signaling and inhibiting myogenic differentiation and muscle regeneration. Therefore, quinine may cause sarcopenia, and this risk should be considered when using quinine for treatment.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 1","pages":"81-90"},"PeriodicalIF":1.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971970","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":"Enhancement of renal fibrosis in PHF20 transgenic mice.","authors":"Uijin Juang, Soohyeon Lee, Suhwan Gwon, Woohyeong Jung, Huonggiang Nguyen, Qingzhi Huang, Beomwoo Lee, So Hee Kwon, Seon-Hwan Kim, In Soo Kim, Jongsun Park","doi":"10.1007/s43188-024-00268-7","DOIUrl":"10.1007/s43188-024-00268-7","url":null,"abstract":"<p><p>Plant homeodomain finger protein 20 (PHF20) plays a crucial role in various biological processes, but its involvement in renal fibrosis remains unclear. This study investigated the role of PHF20 in renal fibrosis using a unilateral ureteral obstruction (UUO) mouse model, a widely accepted model for chronic kidney disease. PHF20 transgenic (PHF20-TG) and wild-type (WT) mice were utilized to explore how PHF20 influences renal inflammation and fibrosis. After UUO surgery, serum analysis revealed elevated creatinine levels and increased inflammatory markers, indicating worsened renal function in PHF20-TG mice. Histological analyses, including H&E, PAS, and Sirius Red staining, confirmed significant tissue damage and fibrosis in the PHF20-TG group. Molecular investigations demonstrated enhanced activation of the TGF-β/SMAD2/3 and NF-κB signaling pathways, both of which are crucial in the progression of renal fibrosis. Our findings suggest that PHF20 overexpression accelerates early-stage renal fibrosis by amplifying inflammatory responses and promoting collagen deposition. This indicates that PHF20 expression could serve as an early marker for renal fibrosis progression.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 1","pages":"71-80"},"PeriodicalIF":1.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972042","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":"Cd stabilizes HIF-1α under normoxic conditions via lysine-63-linked ubiquitination and induces ER stress and cell proliferation.","authors":"Abderrahmen Chargui, Imen Hammami, Abeer Hashem, Amal A Al-Hazzani, Elsayed Fathi Abd Allah, Amin Belaid, Salem Marzougui, Michèle V Elmay, Baharia Mograbi","doi":"10.1007/s43188-024-00266-9","DOIUrl":"10.1007/s43188-024-00266-9","url":null,"abstract":"<p><p>Cadmium, a carcinogenic and toxic substance released into the environment, has emerged as a potent activator of lysine-63 ubiquitination, and lysine-63 is a crucial regulator of signal transduction pathways. Although critical, very little information is currently available about how the activation of lysine 63 ubiquitination by Cd might contribute to cancers and inflammatory diseases. The present study provides the first evidence that Cd stabilizes hypoxia-inducible factor-1-alpha, a transcription factor, under normoxic conditions via lysine 63 ubiquitination. Cd induces the accumulation of lysine 63 polyubiquitinated proteins. Importantly, Cd-induced ubiquitination does not prevent oxidative damage or proteasome impairment. Instead, we demonstrated that Cd activates lysine 63 ubiquitination and amplifies its accumulation by overloading the capacity of the autophagy pathway, thus promoting endoplasmic reticulum stress and cell death. At the molecular level, Cd-induced lysine 63 polyubiquitination is correlated with the stabilization of hypoxia-inducible factor-1-alpha, which translocates into the nucleus and promotes the expression of oncogenes such as interleukin 8 and vascular endothelial growth factor. Strikingly, prolonged cell exposure to high Cd concentrations induces increased lysine-63 polyubiquitination, which promotes aggresome formation, thus preventing this protein from interacting with its downstream nuclear targets. Our results showed that Cd is an activator of K63-linked ubiquitination that stabilizes and promotes the accumulation of HIF-1α, which blocks autophagy, thus resulting in endoplasmic reticulum stress. In addition, a small amount of HIF-1α was observed in the nucleus. We therefore propose that the aberrant activation of lysine 63 polyubiquitination by the carcinogen Cd could promote cell proliferation and inflammation at low levels, while high levels lead to cell death.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-024-00266-9.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 3","pages":"221-234"},"PeriodicalIF":1.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014077","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":"Exploring the various functions of PHD finger protein 20: beyond the unknown.","authors":"Uijin Juang, Suhwan Gwon, Woohyeong Jung, Huonggiang Nguyen, Quingzhi Huang, Soohyeon Lee, Beomwoo Lee, So Hee Kwon, Seon-Hwan Kim, Jongsun Park","doi":"10.1007/s43188-024-00265-w","DOIUrl":"10.1007/s43188-024-00265-w","url":null,"abstract":"<p><p>Over the last decade, the functions of PHD finger protein 20 (PHF20) in several signaling processes have been studied, including those of protein kinase B (PKB)-mediated phosphorylation, p53 regulation, muscle differentiation, and histone modification including histone H3 lysine 4 (H3K4) methylation. One PHF20 human mutation lacks the first nonspecific lethal complex of the component that binds to H3K4me2 to facilitate cancer cell survival. In carcinoma cells, PHF20 expression is regulated by PKB; PHF20 becomes phosphorylated when DNA is damaged, thus inhibiting the p53 activity that maintains cancer cell survival. Given this regulatory effect, PHF20 is usually expressed not only in gliomas but also in breast cancers, colorectal cancers, and other diseases associated with skeletal muscle osteoblastosis and osteoporosis. Thus, PHF20 dysregulation and its downstream effects enhance the abnormalities associated with cancers or other diseases and encourage disease progression. Moreover, PHF20 serves as a nuclear factor kappa-light-chain enhancer of B cell activation, thus increasing pro-inflammatory cytokine production, associated with crosstalk involving the mouse double minute 2 homolog that in turn reduces the normal p53 levels not only in cancers but also in damaged or otherwise injured normal tissues. Despite the findings of various studies, the roles of PHF20 in terms of prognosis, diagnosis, and targeting of disease therapies remain unclear and should be further explored.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 1","pages":"1-11"},"PeriodicalIF":1.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972029","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":"Imatinib mesylate promotes melanogenesis through the modulation of p38 and MITF in murine cells.","authors":"Natchanok Talapphet, Moon-Moo Kim","doi":"10.1007/s43188-024-00267-8","DOIUrl":"10.1007/s43188-024-00267-8","url":null,"abstract":"<p><p>Imatinib mesylate is a targeted anti-cancer drug with skin pigmentation as a side effect. The action mechanism of imatinib mesylate on melanogenesis remains unclear. The purpose of this study was to elucidate the mechanism of imatinib mesylate on melanogenesis associated with the microphthalmia-associated transcription factor (MITF) signaling pathway in murine melanoma cells. This study revealed that imatinib mesylate increased tyrosinase activity but decreased hydrogen peroxide generation in B16F1 cells. Additionally, imatinib mesylate at 0.3-5 μM was nontoxic to the cells and promoted melanin production. Moreover, imatinib mesylate at 5 μM increased the expression levels of TRP-2 and p38 related to melanogenesis compared with the blank group in western blot and immunofluorescence staining analyses. The expression level of p-MITF in the nucleus was increased in the presence of imatinib mesylate compared with the blank group. These results suggest that imatinib mesylate could promote melanogenesis through the modulation of p38 and MITF.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 1","pages":"61-70"},"PeriodicalIF":1.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972033","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":"Rocaglamide-A mitigates LPS-induced hepatic inflammation by modulating JNK/AP-1 signaling cascade and ROS production in hepatocytes.","authors":"Yoon-Su Ha, Taek-Kyong Kim, Jun Heo, Jintaek Oh, Seung-Kyoon Kim, Jeongkyu Kim, Jeonghyung Lee, Se-Ran Yang, Seonghwan Hwang, Seung-Jin Kim","doi":"10.1007/s43188-024-00263-y","DOIUrl":"10.1007/s43188-024-00263-y","url":null,"abstract":"<p><p>Lipopolysaccharide (LPS), a gut-derived endotoxin, is a recognized risk factor for both Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Rocaglamide-A (Roc-A), a natural compound derived from the genus Aglaia, is known for its pharmacological and immunosuppressive effects on various cell types. Although our recent investigations have unveiled Roc-A's anti-adipogenic role in adipocytes, its mechanism in hepatic inflammation remains elusive. This study delves into Roc-A's protective effects on LPS-induced hepatic inflammation. Our results demonstrated that Roc-A treatment significantly reduced the LPS-induced production of inflammatory cytokines in hepatocytes. Intriguingly, Roc-A decreased LPS-induced production of reactive oxygen species (ROS), upregulated antioxidant gene expression, and downregulated endoplasmic reticulum (ER) stress-related gene expression. Mechanistically, Roc-A significantly attenuated LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK) and activator protein-1 (AP-1). Notably, this effect was abolished by the JNK activator Anisomycin, while the JNK inhibitor SP600125 enhanced it. Furthermore, Roc-A suppressed the expression of NF-κB target genes, including inducible nitric oxide synthase (iNOS), thereby alleviating iNOS-derived nitric oxide (NO) production. These findings collectively indicate that Roc-A has the potential to alleviate LPS-induced nitrosative/oxidative stress and hepatic inflammation by inhibiting JNK phosphorylation. Thus, Roc-A emerges as a promising anti-inflammatory intervention for LPS-induced hepatic inflammation.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-024-00263-y.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 1","pages":"47-59"},"PeriodicalIF":1.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972044","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":"Hepatocyte-specific RIG-I loss attenuates metabolic dysfunction-associated steatotic liver disease in mice via changes in mitochondrial respiration and metabolite profiles.","authors":"Jin Kyung Seok, Gabsik Yang, Jung In Jee, Han Chang Kang, Yong-Yeon Cho, Hye Suk Lee, Joo Young Lee","doi":"10.1007/s43188-024-00264-x","DOIUrl":"10.1007/s43188-024-00264-x","url":null,"abstract":"<p><p>Pattern recognition receptor (PRR)-mediated inflammation is an important determinant of the initiation and progression of metabolic diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we investigated whether RIG-I is involved in hepatic metabolic reprogramming in a high-fat diet (HFD)-induced MASLD model in hepatocyte-specific RIG-I-KO (RIG-I^∆hep) mice. Our study revealed that hepatic deficiency of RIG-I improved HFD-induced metabolic imbalances, including glucose impairment and insulin resistance. Hepatic steatosis and liver triglyceride levels were reduced in RIG-I-deficient hepatocytes in HFD-induced MASLD mice, and this was accompanied by the reduced expression of lipogenesis genes, such as PPARγ, Dga2, and Pck1. Hepatic RIG-I deficiency alters whole-body metabolic rates in the HFD-induced MASLD model; there is higher energy consumption in RIG-I^∆hep mice. Deletion of RIG-I activated glycolysis and tricarboxylic acid (TCA) cycle-related metabolites in hepatocytes from both HFD-induced MASLD mice and methionine-choline-deficient diet (MCD)-fed mice. RIG-I deficiency enhanced AMPK activation and mitochondrial function in hepatocytes from HFD-induced MASLD mice. These findings indicate that deletion of RIG-I can activate cellular metabolism in hepatocytes by switching on both glycolysis and mitochondrial respiration, resulting in metabolic changes induced by a HFD and stimulation of mitochondrial activity. In summary, RIG-I may be a key regulator of cellular metabolism that influences the development of metabolic diseases such as MASLD.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-024-00264-x.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"683-695"},"PeriodicalIF":2.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354455","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":"Correction: Upregulation of YPEL3 expression and induction of human breast cancer cell death by microRNAs.","authors":"Boyoung Lee, Yeo-Jung Kwon, Sangyun Shin, Tae-Uk Kwon, Hyemin Park, Hyein Lee, Ji-Heung Kwak, Young-Jin Chun","doi":"10.1007/s43188-024-00261-0","DOIUrl":"https://doi.org/10.1007/s43188-024-00261-0","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1007/s43188-024-00251-2.].</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"697"},"PeriodicalIF":1.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354454","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":"Genotoxicity evaluation of fucoidan-rich <i>Undaria pinnatifida</i> sporophyll.","authors":"Miran Jang, Soo-Im Choi, Gun-Hee Kim","doi":"10.1007/s43188-024-00258-9","DOIUrl":"10.1007/s43188-024-00258-9","url":null,"abstract":"<p><p>The aim of this study was to investigate genotoxicity of fucoidan-rich <i>Undaria pinnatifida</i> sporophyll (FUPS) using a three-component test battery. Our sulfate analysis method showed that FUPS extract contained 14% fucoidan sulfate. The reverse mutation assay showed that the FUPS extract did not increase the number of revertant colonies in any of the five bacterial strains tested, regardless of metabolic activation by S9 mix. Furthermore, FUPS did not induce chromosomal aberrations in the 6-h short-term test with or without S9, as well as in the 24-h continuous test without S9. Finally, bone marrow micronucleus examination of ICR mice at oral doses up to 5000 mg/kg/day did not show a significantly dose-dependent increase in the frequency of micronucleated polychromatic erythrocytes (MNPCEs) or the ratio of polychromatic erythrocytes (PCEs) to total erythrocytes. In conclusion, it was determined that the FUPS extract does not have a significant genotoxic potential under the expected conditions of use.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-024-00258-9.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 1","pages":"39-46"},"PeriodicalIF":1.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972031","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}