Toxicological Research最新文献_第7页

Ruthenium biochanin-A complex ameliorates lung carcinoma through the downregulation of the TGF-β/PPARγ/PI3K/TNF-α pathway in association with caspase-3-mediated apoptosis. 钌-生物素-A复合物通过下调TGF-β/PPARγ/PI3K/TNF-α通路和胱天蛋白酶-3介导的细胞凋亡来改善肺癌。

IF 1.6 4区医学

Toxicological Research Pub Date : 2023-04-15 eCollection Date: 2023-07-01 DOI: 10.1007/s43188-023-00177-1

Ming Cao, Bo Fan, Tianchang Zhen, Abhijit Das, Junling Wang

{"title":"Ruthenium biochanin-A complex ameliorates lung carcinoma through the downregulation of the TGF-β/PPARγ/PI3K/TNF-α pathway in association with caspase-3-mediated apoptosis.","authors":"Ming Cao, Bo Fan, Tianchang Zhen, Abhijit Das, Junling Wang","doi":"10.1007/s43188-023-00177-1","DOIUrl":"10.1007/s43188-023-00177-1","url":null,"abstract":"Lung cancer is the most often reported cancer with a terrible prognosis worldwide. Flavonoid metal complexes have exhibited potential chemotherapeutic effects with substantially low adverse effects. This study investigated the chemotherapeutic effect of the ruthenium biochanin-A complex on lung carcinoma in both in vitro and in vivo model systems. The synthesized organometallic complex was characterized via UV‒visible spectroscopy, FTIR, mass spectrometry, and scanning electron microscopy. Moreover, the DNA binding activity of the complex was determined. The in vitro chemotherapeutic assessment was performed on the A549 cell line through MTT assay, flow cytometry, and western blot analysis. An in vivo toxicity study was performed to determine the chemotherapeutic dose of the complex, and subsequently, chemotherapeutic activity was assessed in benzo-α-pyrene-induced lung cancer mouse model by evaluating the histopathology, immunohistochemistry, and TUNEL assays. The IC50 value of the complex in A549 cells was found to be 20 µM. The complex demonstrated significant apoptosis induction, enhanced caspase-3 expression and cell cycle arrest with downregulated PI3K, PPARγ, TGF-β, and TNF-α expression in A549 cells. The in vivo study suggested that ruthenium biochanin-A therapy restored the morphological architecture of lung tissue in a benzo-α-pyrene-induced lung cancer model and inhibited the expression of Bcl2. Additionally, increased apoptotic events were identified with upregulation of caspase-3 and p53 expression. In conclusion, the ruthenium biochanin-A complex successfully amelioratedlung cancer incidence in both in vitro and in vivo models through the alteration of the TGF-β/PPARγ/PI3K/TNF-α axis with the induction of the p53/caspase-3-mediated apoptotic pathway.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"455-475"},"PeriodicalIF":1.6,"publicationDate":"2023-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743938","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}

引用次数: 0

Exploring scavenger receptor class F member 2 and the importance of scavenger receptor family in prediagnostic diseases. 探索清道夫受体F类成员2和清道夫受体家族在诊断前疾病中的重要性。

IF 1.6 4区医学

Toxicological Research Pub Date : 2023-04-14 eCollection Date: 2023-07-01 DOI: 10.1007/s43188-023-00176-2

Thuy-Trang T Vo, Gyeyeong Kong, Chaeyeong Kim, Uijin Juang, Suhwan Gwon, Woohyeong Jung, Huonggiang Nguyen, Seon-Hwan Kim, Jongsun Park

{"title":"Exploring scavenger receptor class F member 2 and the importance of scavenger receptor family in prediagnostic diseases.","authors":"Thuy-Trang T Vo, Gyeyeong Kong, Chaeyeong Kim, Uijin Juang, Suhwan Gwon, Woohyeong Jung, Huonggiang Nguyen, Seon-Hwan Kim, Jongsun Park","doi":"10.1007/s43188-023-00176-2","DOIUrl":"10.1007/s43188-023-00176-2","url":null,"abstract":"Scavenger Receptor Class F Member 2 (SCARF2), also known as the Type F Scavenger Receptor Family gene, encodes for Scavenger Receptor Expressed by Endothelial Cells 2 (SREC-II). This protein is a crucial component of the scavenger receptor family and is vital in protecting mammals from infectious diseases. Although research on SCARF2 is limited, mutations in this protein have been shown to cause skeletal abnormalities in both SCARF2-deficient mice and individuals with Van den Ende-Gupta syndrome (VDEGS), which is also associated with SCARF2 mutations. In contrast, other scavenger receptors have demonstrated versatile responses and have been found to aid in pathogen elimination, lipid transportation, intracellular cargo transportation, and work in tandem with various coreceptors. This review will concentrate on recent progress in comprehending SCARF2 and the functions played by members of the Scavenger Receptor Family in pre-diagnostic diseases.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"341-353"},"PeriodicalIF":1.6,"publicationDate":"2023-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749088","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}

引用次数: 0

The Wnt/β-catenin signaling pathway plays a role in drug-induced liver injury by regulating cytochrome P450 2E1 expression. Wnt/β-catenin信号通路通过调节细胞色素P4502E1的表达在药物诱导的肝损伤中发挥作用。

IF 1.6 4区医学

Toxicological Research Pub Date : 2023-04-14 eCollection Date: 2023-07-01 DOI: 10.1007/s43188-023-00180-6

Yoo-Sub Shin, Da-Bin Hwang, Dong-Hoon Won, Shin-Young Kim, Changuk Kim, Jun Won Park, Young Jeon, Jun-Won Yun

{"title":"The Wnt/β-catenin signaling pathway plays a role in drug-induced liver injury by regulating cytochrome P450 2E1 expression.","authors":"Yoo-Sub Shin, Da-Bin Hwang, Dong-Hoon Won, Shin-Young Kim, Changuk Kim, Jun Won Park, Young Jeon, Jun-Won Yun","doi":"10.1007/s43188-023-00180-6","DOIUrl":"10.1007/s43188-023-00180-6","url":null,"abstract":"Drug-induced liver injury (DILI) is a major cause of acute liver failure and drug withdrawal. Cytochrome P450 (CYP) 2E1 is involved in the metabolism of several drugs, and can induce liver injury through the production of toxic metabolites and the generation of reactive oxygen species. This study aimed to elucidate the role of Wnt/β-catenin signaling in CYP2E1 regulation for drug-induced hepatotoxicity. To achieve this, mice were administered cisplatin or acetaminophen (APAP) 1 h after treatment with the CYP2E1 inhibitor dimethyl sulfoxide (DMSO), and histopathological and serum biochemical analyses were performed. APAP treatment induced hepatotoxicity, as evidenced by an increase in liver weight and serum ALT levels. Moreover, histological analysis indicated severe injury, including apoptosis, in the liver tissue of APAP-treated mice, which was confirmed by TUNEL assay. Additionally, APAP treatment suppressed the antioxidant capacity of the mice and increased the expression of the DNA damage markers γ-H2AX and p53. However, these effects of APAP on hepatotoxicity were significantly attenuated by DMSO treatment. Furthermore, the activation of Wnt/β-catenin signaling using the Wnt agonist CHIR99021 (CHIR) increased CYP2E1 expression in rat liver epithelial cells (WB-F344), whereas treatment with the Wnt/β-catenin antagonist IWP-2 inhibited nuclear β-catenin and CYP2E1 expression. Interestingly, APAP-induced cytotoxicity in WB-F344 cells was exacerbated by CHIR treatment and suppressed by IWP-2 treatment. Overall, these results showed that the Wnt/β-catenin signaling is involved in DILI through the upregulation of CYP2E1 expression by directly binding the transcription factor β-cat/TCF to the Cyp2e1 promoter, thus exacerbating DILI.Supplementary information: The online version contains supplementary material available at 10.1007/s43188-023-00180-6.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"443-453"},"PeriodicalIF":1.6,"publicationDate":"2023-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743936","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}

引用次数: 0

Dual oxidative stress and fatty acid profile impacts in Paracentrotus lividus exposed to lambda-cyhalothrin: biochemical and histopathological responses. 二元氧化应激和脂肪酸谱对暴露于高效氯氟氰菊酯的鹅掌楸的影响：生化和组织病理学反应。

IF 1.6 4区医学

Toxicological Research Pub Date : 2023-04-13 eCollection Date: 2023-07-01 DOI: 10.1007/s43188-023-00174-4

Chaima Fouzai, Wafa Trabelsi, Safa Bejaoui, Michel Marengo, Feriel Ghribi, Imen Chetoui, Sami Mili, Nejla Soudani

{"title":"Dual oxidative stress and fatty acid profile impacts in Paracentrotus lividus exposed to lambda-cyhalothrin: biochemical and histopathological responses.","authors":"Chaima Fouzai, Wafa Trabelsi, Safa Bejaoui, Michel Marengo, Feriel Ghribi, Imen Chetoui, Sami Mili, Nejla Soudani","doi":"10.1007/s43188-023-00174-4","DOIUrl":"10.1007/s43188-023-00174-4","url":null,"abstract":"Lambda-cyhalothrin (λ-cyh) is a potential pyrethroid insecticide widely used in pest control. The presence of pyrethroids in the aquatic ecosystem may induce adverse effects on non-target organisms such as the sea urchin. This study was conducted to assess the toxic effects of λ-cyh on the fatty acid profiles, redox status, and histopathological aspects of Paracentrotus lividus gonads following exposure to three concentrations of λ-cyh (100, 250 and 500 µg/L) for 72 h. The results showed a significant decrease in saturated fatty acid (SFAs) with an increase in monounsaturated fatty acid (MUFAs) and polyunsaturated fatty acid (PUFAs) levels in λ-cyh treated sea urchins. The highest levels in PUFAs were recorded in the eicosapentaenoic acids (C20:5n-3), docosahexaenoic acids (C22:6n-3) and arachidonic acids (C20:4n-6) levels. The λ-cyh intoxication promoted oxidative stress with an increase in hydrogen peroxide (H2O2), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels. Furthermore, the enzymatic activities and non-enzymatic antioxidants levels were enhanced in all exposed sea urchins, while the vitamin C levels were decreased in 100 and 500 µg/L treated groups. Our biochemical results have been confirmed by the histopathological observations. Collectively, our findings offered valuable insights into the importance of assessing fatty acids' profiles as a relevant tool in aquatic ecotoxicological studies.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"429-441"},"PeriodicalIF":1.6,"publicationDate":"2023-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9737593","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}

引用次数: 0

Immunodysregulatory potentials of polyethylene or polytetrafluorethylene microplastics to mice subacutely exposed via intragastric intubation. 聚乙烯或聚四氟乙烯微塑料对通过胃内插管亚急性暴露的小鼠的免疫失调潜力。

IF 1.6 4区医学

Toxicological Research Pub Date : 2023-04-11 eCollection Date: 2023-07-01 DOI: 10.1007/s43188-023-00172-6

JiHun Jo, Manju Acharya, Pramod Bahadur K C, Anju Maharjan, DaEun Lee, Ravi Gautam, Jung-Taek Kwon, KilSoo Kim, ChangYul Kim, Yong Heo, HyoungAh Kim

{"title":"Immunodysregulatory potentials of polyethylene or polytetrafluorethylene microplastics to mice subacutely exposed via intragastric intubation.","authors":"JiHun Jo, Manju Acharya, Pramod Bahadur K C, Anju Maharjan, DaEun Lee, Ravi Gautam, Jung-Taek Kwon, KilSoo Kim, ChangYul Kim, Yong Heo, HyoungAh Kim","doi":"10.1007/s43188-023-00172-6","DOIUrl":"10.1007/s43188-023-00172-6","url":null,"abstract":"Microplastics (MPs) have been recently recognized as posing a risk to human health. The adverse health effects of MP exposure have been recently reported, especially via the oral exposure route. The present study investigated whether subacute (4 week) exposure to polyethylene (PE) or polytetrafluorethylene (PTFE) MPs via gastric intubation caused immunotoxicity. Two different sizes of PE MPs (6.2 or 27.2 μm) and PTFE MPs (6.0 or 30.5 μm) were administered to 6-week-old mice of both sexes at 0 (corn oil vehicle control), 500, 1000, or 2000 mg/kg/day (n = 4/group). No significant differences were observed between groups in the major thymic or splenic immune cell populations, including thymic CD4+, CD8+, CD4+/CD8+ T lymphocytes, and splenic helper T cells, cytotoxic T cells, and B cells. The ratio of interferon-gamma (IFNγ) to interleukin-4 (IL-4) in culture supernatants from polyclonally activated splenic mononuclear cells ex vivo (48 h) was dose-dependently decreased in female mice that received small- and large-size PTFE MPs. The IFNγ/IL-4 ratio was also decreased in the female mice dosed with large-size PE MPs. The serum IgG2a/IgG1 ratio was dose-dependently increased in male and female animals dosed with small-size PE MPs, in female animals dosed with large-size PTFE MPs, and in male animals dosed with small-size PTFE MPs. The present study implies that immune functions could be affected in animals exposed to MPs via gastric intubation. These effects are dependent on MP size, MP dose, MP polymer type, and mouse sex. Further investigations with longer exposure periods could be necessary to more clearly define the immunotoxic effects of MPs.Supplementary information: The online version contains supplementary material available at 10.1007/s43188-023-00172-6.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"419-427"},"PeriodicalIF":1.6,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749091","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}

引用次数: 0

Toxicologic pathological mechanism of acute lung injury induced by oral administration of benzalkonium chloride in mice. 苯扎氯铵致小鼠急性肺损伤的毒理学病理机制。

IF 1.6 4区医学

Toxicological Research Pub Date : 2023-04-07 eCollection Date: 2023-07-01 DOI: 10.1007/s43188-023-00178-0

Hidehisa Sekijima, Toru Oshima, Yuno Ueji, Naoko Kuno, Yukino Kondo, Saera Nomura, Tomomi Asakura, Kae Sakai-Sugino, Mitsuo Kawano, Hiroshi Komada, Hirokazu Kotani

{"title":"Toxicologic pathological mechanism of acute lung injury induced by oral administration of benzalkonium chloride in mice.","authors":"Hidehisa Sekijima, Toru Oshima, Yuno Ueji, Naoko Kuno, Yukino Kondo, Saera Nomura, Tomomi Asakura, Kae Sakai-Sugino, Mitsuo Kawano, Hiroshi Komada, Hirokazu Kotani","doi":"10.1007/s43188-023-00178-0","DOIUrl":"10.1007/s43188-023-00178-0","url":null,"abstract":"Benzalkonium chloride (BAC) intoxication causes fatal lung injuries, such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the pathogenesis of ALI/ARDS induced by BAC ingestion is poorly understood. This study aimed to clarify the mechanism of lung toxicity after BAC ingestion in a mouse model. BAC was orally administered to C57BL/6 mice at doses of 100, 250, and 1250 mg/kg. After administration, BAC concentrations in the blood and lungs were evaluated via liquid chromatography with tandem mass spectrometry. Lung tissue injury was evaluated via histological and protein analyses. Blood and lung BAC concentration levels after oral administration increased in a dose-dependent manner, with the concentrations directly proportional to the dose administered. The severity of lung injury worsened over time after the oral administration of 1250 mg/kg BAC. An increase in the terminal transferase dUTP nick end labeling-positive cells and cleaved caspase-3 levels was observed in the lungs after 1250 mg/kg BAC administration. In addition, increased cleaved caspase-9 levels and mitochondrial cytochrome c release into the cytosol were observed. These results suggest that lung tissue injury with excessive apoptosis contributes to BAC-induced ALI development and exacerbation. Our findings provide useful information for developing an effective treatment for ALI/ARDS induced by BAC ingestion.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"409-418"},"PeriodicalIF":1.6,"publicationDate":"2023-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749092","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}

引用次数: 0

A comparative study on the implementation of deep learning algorithms for detection of hepatic necrosis in toxicity studies. 深度学习算法在毒性研究中检测肝坏死的实施比较研究。

IF 2.3 4区医学

Toxicological Research Pub Date : 2023-04-06 eCollection Date: 2023-07-01 DOI: 10.1007/s43188-023-00173-5

Ji-Hee Hwang, Minyoung Lim, Gyeongjin Han, Heejin Park, Yong-Bum Kim, Jinseok Park, Sang-Yeop Jun, Jaeku Lee, Jae-Woo Cho

{"title":"A comparative study on the implementation of deep learning algorithms for detection of hepatic necrosis in toxicity studies.","authors":"Ji-Hee Hwang, Minyoung Lim, Gyeongjin Han, Heejin Park, Yong-Bum Kim, Jinseok Park, Sang-Yeop Jun, Jaeku Lee, Jae-Woo Cho","doi":"10.1007/s43188-023-00173-5","DOIUrl":"10.1007/s43188-023-00173-5","url":null,"abstract":"Deep learning has recently become one of the most popular methods of image analysis. In non-clinical studies, several tissue slides are generated to investigate the toxicity of a test compound. These are converted into digital image data using a slide scanner, which is then studied by researchers to investigate abnormalities, and the deep learning method has been started to adopt in this study. However, comparative studies evaluating different deep learning algorithms for analyzing abnormal lesions are scarce. In this study, we applied three algorithms, SSD, Mask R-CNN, and DeepLabV3+, to detect hepatic necrosis in slide images and determine the best deep learning algorithm for analyzing abnormal lesions. We trained each algorithm on 5750 images and 5835 annotations of hepatic necrosis including validation and test, augmented with 500 image tiles of 448 × 448 pixels. Precision, recall, and accuracy were calculated for each algorithm based on the prediction results of 60 test images of 2688 × 2688 pixels. The two segmentation algorithms, DeepLabV3+ and Mask R-CNN, showed over 90% of accuracy (0.94 and 0.92, respectively), whereas SSD, an object detection algorithm, showed lower accuracy. The trained DeepLabV3+ outperformed all others in recall while also successfully separating hepatic necrosis from other features in the test images. It is important to localize and separate the abnormal lesion of interest from other features to investigate it on a slide level. Therefore, we suggest that segmentation algorithms are more appropriate than object detection algorithms for use in the pathological analysis of images in non-clinical studies.Supplementary information: The online version contains supplementary material available at 10.1007/s43188-023-00173-5.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"399-408"},"PeriodicalIF":2.3,"publicationDate":"2023-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10300369","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}

引用次数: 1

Toxicity of a 90-day repeated oral dose of a collagen peptide derived from skate (Raja kenojei) skin: a rat model study. 90天重复口服来源于滑板（Raja kenojei）皮肤的胶原蛋白肽的毒性：大鼠模型研究。

IF 1.6 4区医学

Toxicological Research Pub Date : 2023-03-16 eCollection Date: 2023-07-01 DOI: 10.1007/s43188-023-00175-3

Heung-Sik Seo, Jun-Ho Kim, Sang-Ho Kim, Myeong-Kyu Park, Nak-Won Seong, Geun-Hee Kang, Joong-Sun Kim, Sung-Ho Kim, Jong-Choon Kim, Changjong Moon

{"title":"Toxicity of a 90-day repeated oral dose of a collagen peptide derived from skate (Raja kenojei) skin: a rat model study.","authors":"Heung-Sik Seo, Jun-Ho Kim, Sang-Ho Kim, Myeong-Kyu Park, Nak-Won Seong, Geun-Hee Kang, Joong-Sun Kim, Sung-Ho Kim, Jong-Choon Kim, Changjong Moon","doi":"10.1007/s43188-023-00175-3","DOIUrl":"10.1007/s43188-023-00175-3","url":null,"abstract":"Collagen peptides are widely employed as therapeutic materials due to their numerous beneficial properties, including for the following uses: antiaging, antioxidant applications, antibacterial applications, wound healing, tissue engineering, medication delivery, and cosmetics. Although collagen peptides are useful in these applications, to our knowledge, few published studies have been undertaken on their repeated-dose toxicity. We evaluated the possible subchronic toxicity of a collagen peptide derived from skate (Raja kenojei) skin (CPSS) in Sprague-Dawley rats by administering repeated oral doses over 90 days. Rats of both sexes were assigned randomly to one of four experimental groups, respectively receiving 0, 500, 1000, or 2000 mg/kg/day of CPSS. At all doses tested, repeated oral CPSS administration had no treatment-related adverse effects in terms of clinical signs, body weight, food consumption, detailed clinical observation, sensory reactivity, functional assessment, urinalysis, ophthalmic examination, gross pathology, hematology, serum biochemistry, hormone analysis, organ weight, and histopathology. Even though there were some alterations in hematologic parameters, serum biochemistry parameters, organ weight, and histopathological findings, these did not follow a dose-response pattern and were within historical limits for control rats. The oral no-observed-adverse-effect level (NOAEL) of the CPSS was 2000 mg/kg/day for both male and female rats in the applied experimental circumstances, and no target organs were identified.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"383-398"},"PeriodicalIF":1.6,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749089","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}

引用次数: 0

Effects of stabilizer magnesium nirate on CMIT/MIT-induced respiratory toxicity. 稳定剂nirate镁对CMIT/MIT诱导的呼吸毒性的影响。

IF 2.3 4区医学

Toxicological Research Pub Date : 2023-03-10 eCollection Date: 2023-07-01 DOI: 10.1007/s43188-023-00170-8

Mi-Kyung Song, Yong-Wook Baek, Dong Im Kim, Sung-Hoon Yoon, Kyuhong Lee

{"title":"Effects of stabilizer magnesium nirate on CMIT/MIT-induced respiratory toxicity.","authors":"Mi-Kyung Song, Yong-Wook Baek, Dong Im Kim, Sung-Hoon Yoon, Kyuhong Lee","doi":"10.1007/s43188-023-00170-8","DOIUrl":"10.1007/s43188-023-00170-8","url":null,"abstract":"Despite a humidifier disinfectant (HD) product containing chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) with approximately 22% magnesium nitrate as a stabilizer, no report on the effects of magnesium nitrate on the respiratory toxicity of CMIT/MIT is available. In this study, Kathon CG and Proclin 200, containing approximately 1.5% CMIT/MIT with different magnesium nitrate concentrations (22.6% and 3%, respectively), were used to compare respiratory effects after intratracheal instillation (ITI) in C57BL/6 mice. C57BL/6 mice were randomized into groups of saline control, magnesium nitrate, Kathon CG, and Proclin 200 with 1.14 mg/kg of CMIT/MIT as the active ingredient, and administration was performed 6 times in a 2-3 day-interval in 2 weeks in all groups. Differential cell count analysis, cytokine analysis, and histological analysis of lung tissue were performed to characterize the injury features. Both Kathon and Proclin 200 induced an increase in inflammatory cell levels in the bronchoalveolar lavage (BAL) fluid, in particular, eosinophils and type 2 T helper cell (Th2)-secreted cytokines. All histopathological changes including granulomatous inflammation, mixed inflammatory cell infiltration, mucous cell hyperplasia, eosinophil infiltration, and pulmonary fibrosis were induced with similar frequency and severity in Kathon CG and Proclin 200 groups. Our results suggested that magnesium nitrate did not affect CMIT/MIT-induced lung injury in the intratracheally instilled model. Further inhalation studies are needed to determine the distribution and toxicity differences of CMIT/MIT in the lungs according to the magnesium nitrate concentration.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"373-382"},"PeriodicalIF":2.3,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743940","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}

引用次数: 0

Evaluation of subchronic oral dose toxicity and allergen of freeze-dried powder of Locusta migratoria (Orthoptera: Acrididae) as a novel food source. 作为新型食物来源的蝗虫（直翅目：吖啶科）冻干粉的亚慢性口服剂量毒性和过敏原评估

IF 2.3 4区医学

Toxicological Research Pub Date : 2023-02-15 eCollection Date: 2023-04-01 DOI: 10.1007/s43188-023-00171-7

Sun Young Kim, Kyu-Won Kwak, Ji Yeong Park, Eun-Sung Park, Chun-Ja Nam, Kyu Sup An, Hyun-Jin Kim, Hyung Joo Yoon, Yong-Soon Kim, Kwanho Park, Eunsun Kim, Hyeon Yeol Ryu, Sun-Don Kim

{"title":"Evaluation of subchronic oral dose toxicity and allergen of freeze-dried powder of Locusta migratoria (Orthoptera: Acrididae) as a novel food source.","authors":"Sun Young Kim, Kyu-Won Kwak, Ji Yeong Park, Eun-Sung Park, Chun-Ja Nam, Kyu Sup An, Hyun-Jin Kim, Hyung Joo Yoon, Yong-Soon Kim, Kwanho Park, Eunsun Kim, Hyeon Yeol Ryu, Sun-Don Kim","doi":"10.1007/s43188-023-00171-7","DOIUrl":"10.1007/s43188-023-00171-7","url":null,"abstract":"The migratory locust, Locusta migratoria (Orthoptera: Acrididae), is a well-known edible insect which may serve as new source of human food and animal feed. However, potential toxicity and food safety of L. migratoria had not been investigated extensively until now. Therefore, in this study, we aimed to investigate toxicity of freeze-dried powder of L. migratoria (fdLM) and identify allergic components in ELISA and PCR techniques. In this subchronic study, fdLM was administered once daily by oral gavage at the doses of 750, 1500, and 3000 mg/kg/day. No toxicological changes were observed in both sexes of rats for 13 weeks in accordance with the OECD guidelines and GLP conditions. In addition, fdLM did not induced increases of serum immunoglobulin E and 21 homologous proteins were not detected under our present conditions. In conclusion, the NOAEL (no-observed-adverse-effect level) was 3000 mg/kg/day and no target organ was identified in both sexes. In conclusion, we found that fdLM is safe with no adverse effects and offers the potential of its use as an edible ingredient or other biological uses.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"317-331"},"PeriodicalIF":2.3,"publicationDate":"2023-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9247910","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}

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