Toxicological Research最新文献

{"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}

{"title":"Single and repeated-dose toxicity studies by intravaginal administration of <i>Lactobacillus plantarum</i> ATG-K2 powder in female rats.","authors":"Jae-Hyun Kang, Min-Soo Kang, Sun-Don Kim, Hyun-Kul Lee, Si-Whan Song, Chun-Ja Nam, Kwang-Il Park","doi":"10.1007/s43188-024-00262-z","DOIUrl":"10.1007/s43188-024-00262-z","url":null,"abstract":"<p><p>Bacterial vaginosis (BV) is a microbial dysbiosis that shifts the paradigms of vaginal flora from lactobacilli to opportunistic pathogens. Globally, BV is treated with antibiotic therapy and recurrence rates are > 70% occurring within 6 months due to antibiotic resistance against pathogenic bacteria. An incorporation of <i>lactobacilli</i> orally or intravaginally for the recolonization of healthy microbes in vagina is the suggested course of treatment. Although <i>Lactobacilli</i> are suggested as a novel therapeutic for women's BV, evaluation of safety and toxicity have not been well understood previously. Therefore, in this study, we aimed to evaluate the safety profile of <i>Lactobacillus plantarum</i> ATG-K2 in subacute intravaginal animal toxicity in Sprague-Dawley rats under OECD guidelines and GLP regulations. Toxicological assessments were performed in a single-dose toxicity study by intravaginal administration with local tolerance study, 1-week repeated-dose intravaginal toxicity dose range finding (DRF) study, and a 2-week repeated-dose intravaginal toxicity study with a 2-week recovery period. Studies were performed at dose 3-18 × 10⁹ CFU/head/day. No toxicological changes in clinical signs, body weight, water and food consumption, urinalysis, hematology, clinical biochemistry, gross findings, or histopathological examination were observed in intravaginal repeated-dose toxicity. And <i>Lactobacillus plantarum</i> ATG-K2 did not show any local tolerance at the same doses as the intravaginal repeated-dose toxicity study. In conclusion, the no-observed-adverse-effect level (NOAEL) of <i>Lactobacillus plantarum</i> ATG-K2 was 12 × 10⁹ CFU/head/day and no target organ was identified in female rats. Our findings are the first to suggest that <i>Lactobacillus plantarum</i> is safe for use as an intravaginal treatment with no adverse effects observed in toxicological testing and has potential for application as a therapeutic agent or for other biological uses.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 1","pages":"27-37"},"PeriodicalIF":1.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972048","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":"Evaluation of acute, repeated dose 28-day and 13-week oral toxicity and genotoxicity of a standardized fraction (HemoHIM) from <i>Angelica gigas, Cnidium officinale, and Paeonia lactiflora</i>.","authors":"Ju Gyeong Kim, Su-Bin Bak, Gyoung-Deuck Kim, Han-Sol Choi, Da-Ae Kwon, Ha-Young Kim, Dong-Won Son, Jang-Hun Jeong, Byung-Woo Lee, Hyo-Jin An, Hak Sung Lee","doi":"10.1007/s43188-024-00252-1","DOIUrl":"10.1007/s43188-024-00252-1","url":null,"abstract":"<p><p>HemoHIM is a functional food ingredient comprising a triple herbal combination of extracts from <i>Angelica gigas</i> Nakai, <i>Cnidium officinale</i> Makino, and <i>Paeonia lactiflora</i> Pallas. It was developed to aid the recovery of impaired immune function. Although it is widely used to treat various immune disorders in Korea, its potential toxicity has not been extensively investigated. Therefore, a comprehensive study was conducted to assess the safety of HemoHIM, including acute oral dose toxicity, 28-day and 13-week repeated-dose toxicity, and genotoxicity. To evaluate its safety profile, the dose was increased to 2,000 mg/kg/day, which corresponds to the dose limit for acute toxicity as per the Organization for Economic Cooperation and Development Test Guideline 423. No abnormal findings were observed at the higher doses. For the 28-day and 13-week repeated-dose toxicity studies, HemoHIM was administered at doses of 500, 1,000, and 2,000 mg/kg/day to examine subchronic toxicity in male and female rats. No test item-related clinical signs or mortality was observed at any of the tested doses. Gross pathology, hematology, blood chemistry, and histopathology evaluations further supported the safety of HemoHIM. Therefore, the NOAEL of HemoHIM was considered to be at 2,000 mg/kg/day for both sexes of rats. Bacterial reverse mutation tests, a chromosome aberration test in human peripheral blood lymphocytes, and a mouse micronucleus test were conducted to determine the genotoxicity of HemoHIM, which revealed that HemoHIM was non-mutagenic and non-clastogenic. Collectively, these findings provide valuable evidence to support the safe use of HemoHIM as a functional food ingredient.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 1","pages":"13-26"},"PeriodicalIF":1.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972025","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":"The impact of manganese on vascular endothelium.","authors":"Gustavo H Oliveira-Paula, Airton C Martins, Beatriz Ferrer, Alexey A Tinkov, Anatoly V Skalny, Michael Aschner","doi":"10.1007/s43188-024-00260-1","DOIUrl":"https://doi.org/10.1007/s43188-024-00260-1","url":null,"abstract":"<p><p>Manganese (Mn) is an essential trace element involved in various physiological processes, but excessive exposure may lead to toxicity. The vascular endothelium, a monolayer of endothelial cells within blood vessels, is a primary target of Mn toxicity. This review provides a comprehensive overview of the impact of Mn on vascular endothelium, focusing on both peripheral and brain endothelial cells. In vitro studies have demonstrated that high concentrations of Mn can induce endothelial cell cytotoxicity, increase permeability, and disrupt cell-cell junctions through mechanisms involving oxidative stress, mitochondrial damage, and activation of signaling pathways, such as Smad2/3-Snail. Conversely, low concentrations of Mn may protect endothelial cells from the deleterious effects of high glucose and advanced glycation end-products. In the central nervous system, Mn can cross the blood-brain barrier (BBB) and accumulate in the brain parenchyma, leading to neurotoxicity. Several transport mechanisms, including ZIP8, ZIP14, and SPCA1, have been identified for Mn uptake by brain endothelial cells. Mn exposure can impair BBB integrity by disrupting tight junctions and increasing permeability. In vivo studies have corroborated these findings, highlighting the importance of endothelial barriers in mediating Mn toxicity in the brain and kidneys. Maintaining optimal Mn homeostasis is crucial for preserving endothelial function, and further research is needed to develop targeted therapeutic strategies to prevent or mitigate the adverse effects of Mn overexposure.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"501-517"},"PeriodicalIF":1.6,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354458","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":"Therapeutic strategies for colorectal cancer: antitumor efficacy of dopamine D2 receptor antagonists.","authors":"Sang Hoon Joo, Kyung-Soo Chun","doi":"10.1007/s43188-024-00259-8","DOIUrl":"10.1007/s43188-024-00259-8","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the leading causes of death, accounting for more than half a million deaths annually. Even worse, an increasing number of cancer cases are diagnosed yearly, and two and a half million new cancer cases are estimated to be diagnosed in 2035. Some antipsychotic drugs, especially those targeting dopamine receptor (DR) D2, demonstrated anticancer activity. Studies have revealed the potential of DRD2 antagonists as anticancer therapeutics, whether alone or as an adjuvant, in treating breast cancer, lung cancer, and others. Emerging evidences indicate DRD2 is involved in the CRC biology, and the association between DRD2 and CRC could be utilized in treating CRC. This study selected DRD2 antagonists with anticancer activity to elucidate the possibility of DRD2 antagonists as new therapeutics for treating CRC.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"533-540"},"PeriodicalIF":1.6,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354459","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":"Retraction Note: Flavonoid fractions of diosmin and hesperidin mitigate lead acetate-induced biochemical, oxidative stress, and histopathological alterations in Wistar rats.","authors":"Ibrahim Yusuf Lamidi, Hudu Garba Mikail, Sani Adamu, Isaac Oluwatobi Akefe, Mohammed Bashir Tijjani, Sabo Isa Salihu, Aisha Omobolanle Olatunji, Abdussalam Hassan, Nubwa Daniel, Victoria Aderonke Adegoke","doi":"10.1007/s43188-024-00257-w","DOIUrl":"https://doi.org/10.1007/s43188-024-00257-w","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.1007/s43188-020-00084-9.].</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"701"},"PeriodicalIF":1.6,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354457","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":"Adverse events associated with SARS-CoV-2 neutralizing monoclonal antibodies using the FDA adverse event reporting system database.","authors":"Min Joung Choi, Se-Hun Oh, Yun-Kyoung Song, Sung Hwan Ki","doi":"10.1007/s43188-024-00256-x","DOIUrl":"10.1007/s43188-024-00256-x","url":null,"abstract":"<p><p>The purpose of this study was to analyze the important medical events (IMEs) of anti-severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) monoclonal antibodies using the reports from the United States Food and Drug Administration (US FDA) adverse event reporting system (FAERS) and to detect safety signals. In this study, data from the FAERS from January 2020 to December 2022 were used to investigate signals associated with five monoclonal antibody products (bamlanivimab, bamlanivimab/etesevimab, bebtelovimab, casirivimab/imdevimab, sotrovimab) in coronavirus disease 2019 (COVID-19) patients and one monoclonal antibody product (tixagevimab/cilgavimab) in patients wherein COVID-19 vaccination was not recommended. Disproportionality analyses were conducted using the reporting odds ratio, and an information component to identify safety signals. There were 17,937,860 drug AE reports associated with all drugs in the FAERS documented during research period. Among them, 42,642 were AE reports associated with anti-SARS-CoV-2 monoclonal antibodies. The SOCs including respiratory, thoracic and mediastinal, and vascular disorders were frequently reported for all the six products. The three most commonly detected IMEs were hypoxia, COVID-19 pneumonia, and anaphylactic reaction due to SARS-CoV-2 neutralizing antibodies. Even though the purposes of use were different, the types of signals between drugs were similar. Careful monitoring of these AEs should be considered for certain COVID-19 patients, at risk, when they are treated with monoclonal antibody products.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"673-682"},"PeriodicalIF":1.6,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354452","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":"Acetate attenuates lead-induced dysregulation of testicular steroidogenesis and spermatogenesis by targeting oxidative stress, inflammatory cytokines, and apoptosis.","authors":"Elizabeth Enohnyket Besong, Tunmise Maryanne Akhigbe, Precious Adeoye Oyedokun, Moses Agbomhere Hamed, Roland Eghoghosoa Akhigbe","doi":"10.1007/s43188-024-00250-3","DOIUrl":"10.1007/s43188-024-00250-3","url":null,"abstract":"<p><p>Lead exposure has been implicated in the aetiopathogenesis of male infertility via an oxidative stress-sensitive pathway. Conversely, acetate has been shown to confer cellular protection by improving the antioxidant defense mechanism. Yet, the effect of acetate on lead-induced testicular toxicity, viz., dysregulation of testicular steroidogenesis and spermatogenesis, has not been reported. The present study probed the influence of acetate on lead-induced dysregulation of testicular steroidogenesis and spermatogenesis. In our study, a reduction in body weight gain and testicular weight was identified in lead-exposed rats. While histopathological results established distortion of testicular histoarchitecture, reduced germ cell count, and suppressed spermatogenesis, biochemical studies confirmed that lead-deregulated testicular steroidogenesis was associated with reduced circulating gonadotropin-releasing hormone and gonadotropins, as well as down-regulated testicular 3β-HSD and 17β-HSD activities. These findings were accompanied by increased testicular malondialdehyde, TNF-α, IL-1β, and IL-6, and reduced glutathione, thiol and non-thiol protein levels, total antioxidant capacity, superoxide dismutase, and catalase activities. In addition, lead exposure increased NF<i>k</i>B and Bax levels, as well as caspase 3 activity, but reduced Bcl-2 levels. However, co-administration of acetate ameliorated lead-induced alterations. Collectively, acetate attenuated lead-induced dysregulation of testicular steroidogenesis and spermatogenesis by targeting oxidative stress, NF<i>k</i>B-mediated inflammation, and caspase 3-driven apoptosis.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-024-00250-3.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"613-626"},"PeriodicalIF":1.6,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354451","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 to: Determination of ethanol in blood samples using partial least square regression applied to surface enhanced Raman spectroscopy.","authors":"Güneş Açikgöz, Berna Hamamci, Abdulkadir Yildiz","doi":"10.1007/s43188-024-00245-0","DOIUrl":"https://doi.org/10.1007/s43188-024-00245-0","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.5487/TR.2018.34.2.127.].</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"699"},"PeriodicalIF":1.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354453","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}