Journal of Toxicological Sciences最新文献_第6页

Long-term exposure to urban particulate matter exacerbates mortality after ischemic stroke in mice. 长期暴露于城市颗粒物会加剧小鼠缺血性中风后的死亡率。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.147

Nami Ishihara, Miki Tanaka, Kaede Namba, Shinji Kawano, Sakuno Nishimura, Naoyuki Nezu, Tatsuto Nakane, Ami Oguro, Tomoaki Okuda, Kouichi Itoh, Yu Nabetani, Yasuhiro Ishihara

{"title":"Long-term exposure to urban particulate matter exacerbates mortality after ischemic stroke in mice.","authors":"Nami Ishihara, Miki Tanaka, Kaede Namba, Shinji Kawano, Sakuno Nishimura, Naoyuki Nezu, Tatsuto Nakane, Ami Oguro, Tomoaki Okuda, Kouichi Itoh, Yu Nabetani, Yasuhiro Ishihara","doi":"10.2131/jts.50.147","DOIUrl":"10.2131/jts.50.147","url":null,"abstract":"Exposure to fine particulate matter (PM2.5) has been epidemiologically reported to worsen the prognosis of ischemic stroke; however, the details have not been investigated. One of the major toxic mechanisms of PM2.5 inhalation is oxidative stress, which is mediated by reactive oxygen species generated by PM2.5 components such as metals and polycyclic aromatic hydrocarbons. In this study, we examined the effects of long-term exposure to urban particulate matter, focusing on oxidative stress, on prognosis after ischemic stroke in mice. When mice were intranasally exposed for 28 days to an urban aerosol collected in Beijing, China (CRM28), microglial activation was observed in the cerebral cortex, indicating that CRM28 induced neuroinflammation. CRM28 exposure resulted in increased serum levels of brain natriuretic peptide and troponin I, suggesting that cardiac injury was elicited by CRM28. Lung inflammation was also observed following CRM28 exposure; however, systemic inflammation was not detected. Mice exposed to CRM28 showed an exacerbation of mortality after ischemic stroke induction compared with vehicle mice. A vitamin E-rich diet suppressed CRM28-induced lipid peroxidation in the heart and lungs but not in the brain. A vitamin E-rich diet also attenuated cardiac injury and lung inflammation induced by CRM28 exposure, whereas neuroinflammation was not affected. Mortality after ischemic stroke improved with the administration of a vitamin E-rich diet. Considering that systemic inflammation did not occur, cardiac injury induced by oxidative stress under exposure to urban particulate matter may be involved in increased mortality after ischemic stroke. Antioxidation under air pollution is fundamental for protection against ischemic stroke.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 3","pages":"147-159"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Optimisation of Photo-KeratinoSens™ for in vitro photoallergenicity assessment. photokeratinosens™体外光致敏性评估的优化。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.399

Tomomi Atobe, Suttinont Chawapun, Yuri Hatakeyama, Shiho Oeda, Toshiyuki Ohtake, Takao Ashikaga, Hirokazu Kouzuki, Morihiko Hirota, Akiko Tamura

{"title":"Optimisation of Photo-KeratinoSens™ for in vitro photoallergenicity assessment.","authors":"Tomomi Atobe, Suttinont Chawapun, Yuri Hatakeyama, Shiho Oeda, Toshiyuki Ohtake, Takao Ashikaga, Hirokazu Kouzuki, Morihiko Hirota, Akiko Tamura","doi":"10.2131/jts.50.399","DOIUrl":"https://doi.org/10.2131/jts.50.399","url":null,"abstract":"The aim of this work was to develop and validate a cell-based in vitro assay for predicting photoallergenicity by expanding the scope of our previously reported in vitro method, photo-KeratinoSens™, which is a luciferase-based assay dependent on activation of the Keap1-Nrf2-ARE pathway. First, we increased the maximum starting test concentration from a fixed 2000 µM in the original KeratinoSens™ to either 5000 μg/mL or 4 times the concentration providing a cell viability of 75% (under UV irradiation), depending on the cytotoxicity. Then, we established that 0.5% ethanol, 0.5% acetone and 0.1% tetrahydrofuran are available as solvents in addition to 1% DMSO, which is used in the standard KeratinoSens™ method (OECD TG442D). We confirmed that a representative photoallergen, 6-methylcoumarin, gave reproducible results. To validate the developed assay, we used it to evaluate a library of 90 chemicals consisting of 60 known photoallergens and 30 non-photoallergens. The accuracy, sensitivity, specificity and balanced accuracy of photo-KeratinoSens™ were 76.7% (69/90), 66.7% (40/60), 96.7% (29/30) and 81.7%, respectively. When we excluded chemicals with no UVA absorption, the accuracy, sensitivity, specificity and balanced accuracy were improved to 81.8% (45/55), 80.0% (36/45), 90.0% (9/10) and 85%, respectively. Our results suggest that photo-KeratinoSens™, which combines the OECD TG442D in vitro skin sensitization test detecting key event 2 in the adverse outcome pathway (AOP) of skin sensitization with exposure to UV iradiation, may be useful as a contributory input in a weight-of-evidence approach for evaluating photoallergenicity potential without animal testing.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 8","pages":"399-412"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

A probabilistic approach for estimating human exposure to polychlorinated biphenyls via tuna consumption. 估计人类因食用金枪鱼而暴露于多氯联苯的概率方法。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.493

Muhammad Zeeshan Jamil, Jinrui Zhao, Yoshiki Nishi, Oishe Sadia Noon

引用次数: 0

Expression profiles of purinergic P1 and P2 receptors in cultured bovine aortic endothelial cells, bovine aortic smooth muscle cells, and human vascular endothelial EA.hy926 cells. 嘌呤能P1和P2受体在培养的牛主动脉内皮细胞、牛主动脉平滑肌细胞和人血管内皮EA.hy926细胞中的表达谱

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.583

Lihito Ikeuchi, Takato Hara, Kazuki Kitabatake, Fumiaki Uchiumi, Chika Yamamoto, Mitsutoshi Tsukimoto, Tomoya Fujie, Toshiyuki Kaji

{"title":"Expression profiles of purinergic P1 and P2 receptors in cultured bovine aortic endothelial cells, bovine aortic smooth muscle cells, and human vascular endothelial EA.hy926 cells.","authors":"Lihito Ikeuchi, Takato Hara, Kazuki Kitabatake, Fumiaki Uchiumi, Chika Yamamoto, Mitsutoshi Tsukimoto, Tomoya Fujie, Toshiyuki Kaji","doi":"10.2131/jts.50.583","DOIUrl":"https://doi.org/10.2131/jts.50.583","url":null,"abstract":"Purinergic signaling plays an important role in vascular biology by vascular tone, inflammation, and remodeling through extracellular nucleotides that activate the P1 and P2 receptors. However, the expression patterns of these receptors in commonly used vascular cell models are not well characterized. In this study, we examined purinergic receptor expression in bovine aortic endothelial cells (BAECs), bovine aortic smooth muscle cells (BASMCs), and human vascular endothelial EA.hy926 cells. In BAECs, ADORA2A, ADORA2B, P2X4R, P2X7R, P2Y1R, P2Y2R, P2Y4R, P2Y6R, and P2Y11R were expressed, whereas the other purinergic receptors were not. BASMCs expressed ADORA2A, ADORA2B, P2X4R, P2X5R, P2Y1R, P2Y2R, P2Y6R, and P2Y11R. EA.hy926 cells expressed ADORA2A, ADORA2B, P2X4R, P2Y2R, P2Y6R, and P2Y11R. These results showed distinct expression profiles of purinergic receptors across different cell types. BAECs exhibited a purinergic receptor expression pattern similar to that of primary human vascular endothelial cells, suggesting that BAECs are a suitable model for studying purinergic signaling in vascular endothelial cells.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 10","pages":"583-591"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Discovery and development of COVID-19 vaccines and therapeutics: nonclinical perspectives. COVID-19 疫苗和疗法的发现与开发：非临床视角。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.79

Nasir Khan, Jean Sathish, Cynthia M Rohde

{"title":"Discovery and development of COVID-19 vaccines and therapeutics: nonclinical perspectives.","authors":"Nasir Khan, Jean Sathish, Cynthia M Rohde","doi":"10.2131/jts.49.79","DOIUrl":"10.2131/jts.49.79","url":null,"abstract":"The development and regulatory review of BNT162b2, a COVID-19 vaccine, and PaxlovidTM (nirmatrelvir tablets/ritonavir tablets), a COVID-19 therapeutic, are benchmarks for accelerated innovation during a global pandemic. Rapid choice of the SARS-CoV-2 spike protein and main protease (Mpro) as targets for the vaccine and therapeutic, respectively, leveraged the available knowledge of the biology of SARS-CoV-2 and related viruses. The nonclinical immunogenicity and safety of BNT162b2 was rigorously assessed. Likewise, a comprehensive nonclinical safety assessment was conducted for the therapeutic candidates, lufotrelvir (PF-07304814) and nirmatrelvir (PF-07321332). The development and regulatory review of BNT162b2 and Paxlovid was enabled through close collaboration of the pharmaceutical industry with regulatory agencies and public health organizations. This experience highlights approaches that could be adopted for pandemic preparedness including risk-based investment strategies, conduct of activities in parallel that normally are conducted sequentially, quick kill decisions, simultaneous evaluation of multiple candidates, and use of flexible, established vaccine platforms.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 3","pages":"79-94"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Comparison of the fecal bacterial microbiota in mice, rats, and pigs after oral administration of alpha-glycosyl isoquercitrin. 比较小鼠、大鼠和猪口服α-糖基异槲皮素后的粪便细菌微生物群。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.151

Hong Liu, Ryo Inoue, Mihoko Koyanagi, Shim-Mo Hayashi, Gen Watanabe, Kentaro Nagaoka

{"title":"Comparison of the fecal bacterial microbiota in mice, rats, and pigs after oral administration of alpha-glycosyl isoquercitrin.","authors":"Hong Liu, Ryo Inoue, Mihoko Koyanagi, Shim-Mo Hayashi, Gen Watanabe, Kentaro Nagaoka","doi":"10.2131/jts.49.151","DOIUrl":"10.2131/jts.49.151","url":null,"abstract":"Alpha-glycosyl isoquercitrin (AGIQ) is composed of isoquercitrin and its glucosylated derivatives and has many biological activities, including anti-inflammatory, antioxidant, and anti-cancer properties. However, the effect of AGIQ administered orally on gut microbiota composition remains unclear. The objective of this study was to evaluate the effect of AGIQ on the gut microbiota of animals in different dose groups. Male rats and mice received different doses of AGIQ (1.5%, 3%, or 5% w/v) in diet for carcinogenic or chronic toxicity studies (rasH2 mice: 6 months; Sprague-Dawley rats: 12 months). Male minipigs received 100, 300, or 1000 mg/kg/day for 28 days. Fecal samples were collected from the different animal species and analyzed using 16S-rRNA gene sequencing. No significant changes were observed in alpha and beta diversity of the gut microbiota. Characteristic bacteria that responded to AGIQ were identified in each animal species, and, interestingly, Kineothrix alysoides, a butyrate-producing bacterium, was commonly detected in all three species, suggesting that it may be related to the biological activities of AGIQ. AGIQ selectively modulated the number of beneficial butyrate-producing commensal bacterium beneficial bacteria without changing the diversity of gut microbiota, which further supports the safe use of AGIQ in food products.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 4","pages":"151-161"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Integrating mathematical approaches (IMAS): Novel methodology for predicting dermal absorption rates of chemicals under finite dose conditions. 综合数学方法（IMAS）：在有限剂量条件下预测化学品皮肤吸收率的新方法。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.219

Ryoki Kunita, Takafumi Nishijima, Hiroaki Todo, Masaaki Miyazawa

{"title":"Integrating mathematical approaches (IMAS): Novel methodology for predicting dermal absorption rates of chemicals under finite dose conditions.","authors":"Ryoki Kunita, Takafumi Nishijima, Hiroaki Todo, Masaaki Miyazawa","doi":"10.2131/jts.49.219","DOIUrl":"https://doi.org/10.2131/jts.49.219","url":null,"abstract":"Quantitative structure permeation relationship (QSPR) models have gained prominence in recent years owing to their capacity to elucidate the influence of physicochemical properties on the dermal absorption of chemicals. These models facilitate the prediction of permeation coefficient (Kp) values, indicating the skin permeability of a chemical under infinite dose conditions. Conversely, obtaining dermal absorption rates (DAs) under finite dose conditions, which are crucial for skin product safety evaluation, remains a challenge when relying solely on Kp predictions from QSPR models. One proposed resolution involves using Kroes' methodology, categorizing DAs based on Kp values; however, refinement becomes necessary owing to discreteness in the obtained values. We previously developed a mathematical model using Kp values obtained from in vitro dermal absorption tests to predict DAs. The present study introduces a new methodology, Integrating Mathematical Approaches (IMAS), which combines QSPR models and our mathematical model to predict DAs for risk assessments without conducting in vitro dermal absorption tests. Regarding 40 chemicals (76.1 ≤ MW ≤ 220; -1.4 ≤ Log Ko/w ≤ 3.1), IMAS showed that 65.0% (26/40) predictions of DA values were accurate to within twofold of the observed values in finite dose experiments. Compared to Kroes' methodology, IMAS notably mitigated overestimation, particularly for hydrophilic chemicals with water solubility exceeding 57.0 mg/cm3. These findings highlight the value of IMAS as a tool for skin product risk assessments, particularly for hydrophilic compounds.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 5","pages":"219-230"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Lung carcinogenicity by whole body inhalation exposure to Anatase-type Nano-titanium Dioxide in rats. 大鼠全身吸入 Anatase 型纳米二氧化钛对肺部的致癌性。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.359

Tatsuya Kasai, Shigeyuki Hirai, Yuske Furukawa, Kyouhei Misumi, Tomoki Takeda, Yuko Goto, Kenji Takanobu, Kengo Yoneyama, Shotaro Yamano, Hideki Senoh, Yumi Umeda

{"title":"Lung carcinogenicity by whole body inhalation exposure to Anatase-type Nano-titanium Dioxide in rats.","authors":"Tatsuya Kasai, Shigeyuki Hirai, Yuske Furukawa, Kyouhei Misumi, Tomoki Takeda, Yuko Goto, Kenji Takanobu, Kengo Yoneyama, Shotaro Yamano, Hideki Senoh, Yumi Umeda","doi":"10.2131/jts.49.359","DOIUrl":"https://doi.org/10.2131/jts.49.359","url":null,"abstract":"To investigate the carcinogenicity of anatase-type nano-titanium dioxide (aNTiO2), F344/DuCrlCrlj rats were exposed to aNTiO2 aerosol at concentrations of 0, 0.5, 2, and 8 mg/m3. The rats were divided into 2 groups: carcinogenicity study groups were exposed for two years, and satellite study groups were exposed for one year followed by recovery for 1 day, 26 weeks, and 52 weeks after the end of exposure. In the carcinogenicity groups, bronchiolo-alveolar carcinomas were observed in two 8 mg/m3-exposed males, showing an increasing trend by Peto's test. However, this incidence was at the upper limit of JBRC's historical control data. Bronchiolo-alveolar adenomas were observed in 1, 2, 3, and 4 rats of the 0, 0.5, 2, and 8 mg/m3-exposed females and were not statistically significant. However, the incidence in the 8 mg/m3-exposed females exceeded JBRC's historical control data. Therefore, we conclude there is equivocal evidence for the carcinogenicity of aNTiO2 in rats. No lung tumors were observed in the satellite groups. Particle-induced non-neoplastic lesions (alveolar epithelial hyperplasia and focal fibrosis) were observed in exposed males and females in both the carcinogenicity and satellite groups. Increased lung weight and neutrophils of bronchoalveolar lavage fluid were observed in the 8 mg/m3-exposed carcinogenicity groups. The aNTiO2 deposited in the lungs of the satellite group rats was decreased at 26 weeks after the end of exposure compared to 1 day after the end of exposure. At 52 weeks after the end of exposure, the decreased level was the same at 26 weeks after the end of exposure.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 8","pages":"359-383"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Investigation of normalization procedures for transcriptome profiles of compounds oriented toward practical study design. 以实用研究设计为导向的化合物转录组图谱归一化程序研究。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.249

Tadahaya Mizuno, Hiroyuki Kusuhara

{"title":"Investigation of normalization procedures for transcriptome profiles of compounds oriented toward practical study design.","authors":"Tadahaya Mizuno, Hiroyuki Kusuhara","doi":"10.2131/jts.49.249","DOIUrl":"https://doi.org/10.2131/jts.49.249","url":null,"abstract":"The transcriptome profile is a representative phenotype-based descriptor of compounds, widely acknowledged for its ability to effectively capture compound effects. However, the presence of batch differences is inevitable. Despite the existence of sophisticated statistical methods, many of them presume a substantial sample size. How should we design a transcriptome analysis to obtain robust compound profiles, particularly in the context of small datasets frequently encountered in practical scenarios? This study addresses this question by investigating the normalization procedures for transcriptome profiles, focusing on the baseline distribution employed in deriving biological responses as profiles. Firstly, we investigated two large GeneChip datasets, comparing the impact of different normalization procedures. Through an evaluation of the similarity between response profiles of biological replicates within each dataset and the similarity between response profiles of the same compound across datasets, we revealed that the baseline distribution defined by all samples within each batch under batch-corrected condition is a good choice for large datasets. Subsequently, we conducted a simulation to explore the influence of the number of control samples on the robustness of response profiles across datasets. The results offer insights into determining the suitable quantity of control samples for diminutive datasets. It is crucial to acknowledge that these conclusions stem from constrained datasets. Nevertheless, we believe that this study enhances our understanding of how to effectively leverage transcriptome profiles of compounds and promotes the accumulation of essential knowledge for the practical application of such profiles.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 6","pages":"249-259"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Paternal methamphetamine exposure differentially affects first and second generations in mice. 父代甲基苯丙胺对小鼠第一代和第二代的影响不同。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.9

Sakiko Munetomo-Aoki, Asuka Kaizaki-Mitsumoto, Ryota Nakano, Satoshi Numazawa

{"title":"Paternal methamphetamine exposure differentially affects first and second generations in mice.","authors":"Sakiko Munetomo-Aoki, Asuka Kaizaki-Mitsumoto, Ryota Nakano, Satoshi Numazawa","doi":"10.2131/jts.49.9","DOIUrl":"https://doi.org/10.2131/jts.49.9","url":null,"abstract":"Amphetamine-type stimulants are abused worldwide, and methamphetamine (METH) accounts for a large majority of seized abused drug cases. Recently, the paternal origin of health and disease theory has been proposed as a concept wherein paternal factors influence descendants. Although METH abuse is more common among males, its effects on their descendants were not examined. Therefore, we investigated the effects of paternal METH exposure on F1 and F2 levels in a mouse model. Sires were administered METH for 21 days and mated with female mice to obtain F1 mice. Growth evaluations (number of births, survival rate, body weight, righting reflex, cliff avoidance tests, and wire-hanging maneuver) were performed on F1 mice. Upon reaching six weeks of age, the mice were subjected to spontaneous locomotion, elevated plus-maze, acute METH treatment, and passive avoidance tests. Additionally, RNA-seq was performed on the striatum of male mice. Male F1 mice were mated with female mice to obtain F2 mice. They were subjected to the same tests as the F1 mice. Paternal METH exposure resulted in delayed growth and decreased memory function in F1 mice, overweight in F2 mice, decreased METH sensitivity, and reduced anxiety-related behaviors in female F2 mice. Enrichment analysis revealed significant enrichment of terms related to behavior in F1 and protein folding in F2. These results indicated that the effects of paternal METH exposure vary across generations. The effects of paternal factors need to be examined not only in F1, but also in F2 and beyond.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 1","pages":"9-26"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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