Journal of Toxicological Sciences最新文献_第8页

Coptisine improves sepsis-induced acute kidney injury by inhibiting ferroptosis. 黄柏碱通过抑制铁下垂改善脓毒症引起的急性肾损伤。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.649

Yu Zhang, Junjun Huang, Xiaoyan Ji, Ke Ren

{"title":"Coptisine improves sepsis-induced acute kidney injury by inhibiting ferroptosis.","authors":"Yu Zhang, Junjun Huang, Xiaoyan Ji, Ke Ren","doi":"10.2131/jts.50.649","DOIUrl":"https://doi.org/10.2131/jts.50.649","url":null,"abstract":"Sepsis-associated acute kidney injury (SA-AKI) is a life-threatening complication characterized by high morbidity and mortality. However, effective pharmacological therapies are currently unavailable. Ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in the pathogenesis of SA-AKI. Coptisine, a natural isoquinoline alkaloid derived from Coptis chinensis, has demonstrated anti-inflammatory and antioxidant effects, but its specific role in SA-AKI remains to be elucidated. In this study, we investigated the protective effects of Coptisine against SA-AKI and the underlying mechanisms involved. Using a cecal ligation and puncture (CLP) mouse model, our study revealed that administering Coptisine significantly alleviated renal injury and inflammation, decreased oxidative stress, and inhibited ferroptosis in kidney tissues. In vitro studies showed that Coptisine suppressed LPS-induced ferroptotic injury in HK2 cells. Nevertheless, this protective effect was reversed by Nrf2 knockdown or iron supplementation. Mechanistically, Coptisine upregulated the levels of Nrf2 and GPX4, resulting in reduced ROS, MDA, and Fe2+ levels, while enhancing GSH content. Collectively, our findings indicate that Coptisine alleviates sepsis-induced AKI by inhibiting ferroptosis through the activation of the Nrf2 signaling pathway, highlighting its potential as a therapeutic agent for SA-AKI.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 12","pages":"649-659"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145648849","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

Effects of food restriction and sex hormonal intervention on alkaline phosphatase isoenzymes in serum, liver, bone and small intestine of rats. 限食和性激素干预对大鼠血清、肝脏、骨骼和小肠碱性磷酸酶同工酶的影响。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.661

Aya Hasegawa-Izaki, Junya Morita, Yuka Kirihata, Natsuki Tanaka, Chihiro Noguchi, Kenta Matsue, Yasuhiro Kurihara, Satoshi Tsuji, Aiko Ishii, Masaki Wakamatsu

{"title":"Effects of food restriction and sex hormonal intervention on alkaline phosphatase isoenzymes in serum, liver, bone and small intestine of rats.","authors":"Aya Hasegawa-Izaki, Junya Morita, Yuka Kirihata, Natsuki Tanaka, Chihiro Noguchi, Kenta Matsue, Yasuhiro Kurihara, Satoshi Tsuji, Aiko Ishii, Masaki Wakamatsu","doi":"10.2131/jts.50.661","DOIUrl":"https://doi.org/10.2131/jts.50.661","url":null,"abstract":"To investigate the effects of reduced food intake on the serum and tissue levels of alkaline phosphatase (ALP) isoenzymes in rats, ALP1, ALP2, ALP3, and ALP5 were analyzed in serum, liver, bone, and small intestine of male and female Sprague-Dawley rats reared under a diet-restricted condition (fed 65% or 45% of the amount of the free-feeding group) for 4 weeks from six-week-old. In addition, to examine the effect of sex hormonal, each ALP isoenzyme level was also analyzed in free-feeding female rats with ovariectomy or testosterone administration. Food restriction was associated with the following changes: an increase of the serum ALP5 level in the females, mainly caused by an increase derived from the small intestine; increases in the liver ALP1 and small intestinal ALP5 levels in both sexes, which represented a compensatory increase of these ALP isoenzyme levels to enhance lipid absorption under the low nutritional condition; a decrease of the bone ALP3 level in females, which was considered reflective of suppressed bone formation. Regarding the sex differences, serum ALP2 and liver ALP1 levels were higher in the males than in the females; the levels in ovariectomized or testosterone-treated females shifted closer to those in the males. These results indicate that food restriction and sex hormonal intervention influenced the serum and tissue ALP isoenzyme levels in rats. These findings provide helpful information for understanding the effects of reduced food intake, often observed in toxicity studies, and sex differences in rats on ALP and help to properly evaluate the effects of test compounds.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 12","pages":"661-675"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145648895","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

Benzalkonium chloride initiates proinflammatory responses via NLRP3 inflammasome activation. 苯扎氯铵通过NLRP3炎性体激活引发促炎反应。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.11

Tomohiro Kagi, Maoko Tan, Wakana Suzuki, Kohei Otani, Sara Suzuki, Yusuke Hirata, Takuya Noguchi, Atsushi Matsuzawa

{"title":"Benzalkonium chloride initiates proinflammatory responses via NLRP3 inflammasome activation.","authors":"Tomohiro Kagi, Maoko Tan, Wakana Suzuki, Kohei Otani, Sara Suzuki, Yusuke Hirata, Takuya Noguchi, Atsushi Matsuzawa","doi":"10.2131/jts.50.11","DOIUrl":"https://doi.org/10.2131/jts.50.11","url":null,"abstract":"A representative surfactant, benzalkonium chloride (BAC) is used as a disinfectant, but sometimes causes serious side effects, including lung disorders such as interstitial pneumonia. However, its pathogenic mechanisms remain unexplained. In this study, we identified a novel mechanism by which BAC initiates inflammatory responses that may be responsible for its side effects. We firstly investigated whether BAC initiates inflammation, and found that BAC promotes the secretion of the pro-inflammatory cytokine interleukin-1β (IL-1β) but not tumor necrosis factor-α (TNF-α) in macrophages. Interestingly, the IL-1β secretion triggered by the surfactants was completely blocked by the K-ATP channel blocker glibenclamide or the calcium chelating agent 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA)-AM. Moreover, genetic experiments revealed that BAC-dependent IL-1β secretion is mediated by the NLRP3 inflammasome. These results suggest that derangement of ion fluxes associated with the interfacial effects of BAC triggers NLRP3 inflammasome activation and subsequent inflammation. Thus, the NLRP3-dependent mechanisms triggered by BAC may explain the pathogenesis of surfactant-caused adverse effects.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 1","pages":"11-21"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950772","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

Incorporation of target safety review in drug discovery. 药物发现过程中靶标安全性评价的结合。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.593

Yuichiro Amano, Brandon Jeffy, Hisashi Anayama, Jodi Goodwin

{"title":"Incorporation of target safety review in drug discovery.","authors":"Yuichiro Amano, Brandon Jeffy, Hisashi Anayama, Jodi Goodwin","doi":"10.2131/jts.50.593","DOIUrl":"https://doi.org/10.2131/jts.50.593","url":null,"abstract":"Ensuring the safety of new pharmaceuticals and therapies is paramount in drug discovery. Takeda's Discovery Toxicology plays a crucial role in reducing safety-related risks by focusing on the quality of drug discovery targets. This involves identifying potential toxicities early in the development phase, enabling the mitigation of risks before they impact later stages of drug development. The Target Safety Review (TSR) initiates the Target Safety Assessment (TSA) process, providing a strategic assessment of safety concerns arising from target modulation. The TSR types range from comprehensive evaluations to simplified versions, assessing on-target and off-target effects, project background, biological information, and chemistry. Importantly, the TSR includes risk ranking and de-risking plans. Risks are ranked based on their probability and impact, enabling informed decision-making throughout the drug development process. This minireview discusses several case studies at Takeda, illustrating the importance of early risk identification. Of course, challenges remain, such as the appropriate timing of TSR creation, limited human on-target information, the need for effective risk assessment methods, incorporation of safety indicators into pharmacological studies, and addressing specific background risks in patient populations. Nonetheless, utilizing the TSR and TSA processes ensures a streamlined and safer drug development journey and provides a comprehensive approach to effectively address potential safety risks.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 11","pages":"593-599"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437846","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

Lenvatinib induces diarrhea in rats by promoting intestinal barrier injury via targeting AQP4. Lenvatinib通过靶向AQP4促进肠屏障损伤诱导大鼠腹泻。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.677

Guanbao Long, Xin Li, Chaowen Xiao, Lu Tan, Changchun Cai

{"title":"Lenvatinib induces diarrhea in rats by promoting intestinal barrier injury via targeting AQP4.","authors":"Guanbao Long, Xin Li, Chaowen Xiao, Lu Tan, Changchun Cai","doi":"10.2131/jts.50.677","DOIUrl":"https://doi.org/10.2131/jts.50.677","url":null,"abstract":"Our study evaluated whether lenvatinib induces the disease process of diarrhea by facilitating intestinal epithelial barrier damage. Sprague-Dawley rats were orally administrated with 0.2 or 2 mg/kg lenvatinib for six consecutive days to induce diarrhea models. The diarrhea rate was monitored every day, and rats were sacrificed on day 6. We found that rats began to develop diarrhea on day 3 after lenvatinib treatment. Almost all rats treated with lenvatinib (2 mg/kg) developed grade 3 diarrhea. Intestinal villi structure damage and obvious inflammatory cell infiltration were observed in the colon tissues of lenvatinib-administrated rats. Lenvatinib significantly upregulated serum contents of intestinal injury biomarkers (D-lactate and DAO) but downregulated colon levels of tight junction proteins (ZO-1, Occludin, and Claudin-1) in rats. In vitro results showed that lenvatinib higher than 5 μM significantly attenuated the viability of human intestinal epithelial cell line Caco-2. Lenvatinib suppressed ZO-1, Occludin, and Claudin-1 levels, decreased the transepithelial electrical resistance value, and elevated paracellular permeability in Caco-2 cells. Mechanically, lenvatinib targeted AQP4 and inhibited its expression. Overexpressing AQP4 reversed lenvatinib-induced intestinal epithelial barrier injury in Caco-2 cells by inhibiting the MLCK/p-MLC2 signaling pathway. Collectively, lenvatinib triggers diarrhea by disrupting the intestinal barrier through downregulating AQP4 and activating the MLCK/p-MLC2 signaling pathway.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 12","pages":"677-690"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145648841","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

Renal effects of excessive fructose intake in Spontaneously Diabetic Torii-Leprfa (SDT fatty) rats. 过量果糖摄入对自发性糖尿病Torii-Leprfa （SDT脂肪）大鼠肾脏的影响。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.727

Kaoru Toyoda, Tadakazu Takahashi, Yuki Tanaka, Yusuke Suzuki, Hideaki Yokoyama, Toshiyuki Shoda, James K Chambers, Kazuyuki Uchida

{"title":"Renal effects of excessive fructose intake in Spontaneously Diabetic Torii-Leprfa (SDT fatty) rats.","authors":"Kaoru Toyoda, Tadakazu Takahashi, Yuki Tanaka, Yusuke Suzuki, Hideaki Yokoyama, Toshiyuki Shoda, James K Chambers, Kazuyuki Uchida","doi":"10.2131/jts.50.727","DOIUrl":"https://doi.org/10.2131/jts.50.727","url":null,"abstract":"Excessive fructose intake has been reported to increase the risks of obesity, diabetes and kidney diseases, including diabetic nephropathy. We investigated the effects of a high-fructose diet on nephropathy in both male and female Spontaneously Diabetic Torii-Leprfa (SDT fatty) rats, a model for obese type 2 diabetes. 11-week-old male and female Sprague-Dawley (SD) and SDT fatty rats that developed diabetes were each divided into 2 groups receiving either a high-fructose diet (60% fructose) or a basal diet. The diets were fed ad libitum for 7 weeks. Body weights, food consumption, clinical chemistry, urinalysis, kidney weights and histopathology of the kidneys were evaluated. In the SDT fatty rats, fructose intake increased the urinary excretion of calcium and inorganic phosphate in both sexes. Histopathological examination revealed that fructose intake worsened nephropathy (mineralization, inflammatory cell infiltration, and increased mesangial matrix in the glomeruli) in the female SDT fatty rats. In conclusion, a 7-week high-fructose diet induced several renal changes in SDT fatty rats, including urinary electrolyte imbalances and associated mineral deposition in the kidney, suggestive of urinary stone formation. It suggests that the SDT fatty rat is a useful model to investigate type 2 diabetes and diabetic nephropathy and that excessive fructose intake can be a risk factor for the development and progression of urinary stone formation and diabetes- related kidney injury.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 12","pages":"727-740"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145648866","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

Activation of the arylhydrocarbon receptor through maternal beta-naphthoflavone exposure in the neonatal kidney. 新生儿肾脏中母体β -萘黄酮暴露对芳烃受体的激活作用。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.161

Wataru Yoshioka, Kanta Kikutake

{"title":"Activation of the arylhydrocarbon receptor through maternal beta-naphthoflavone exposure in the neonatal kidney.","authors":"Wataru Yoshioka, Kanta Kikutake","doi":"10.2131/jts.50.161","DOIUrl":"10.2131/jts.50.161","url":null,"abstract":"The kidneys of neonates are vulnerable to stressors due to their immature structure and function. Excess activation of the transcription factor arylhydrocarbon receptor (AhR) in the kidneys of neonates can cause severe hydronephrosis, as shown previously using 2,3,7,8-tetrachlorodibenzo-p-dioxin, an AhR agonist. In this study, we aimed to clarify the conditions under which AhR activation leads to hydronephrosis using beta-naphthoflavone (BNF), another potent agonist of AhR. Mouse dams were fed a BNF-containing diet, and the kidneys of their pups were examined. Maternal BNF exposure on postnatal day 1 (PND 1) significantly activated AhR, as evidenced by the increased mRNA levels of the target genes. However, AhR activation was hardly detectable on PND 2 or subsequent days although the mice were continually fed the BNF-containing diet. Further, no hydronephrosis or a related alteration was observed. Similarly, maternal BNF exposure from PND 6 induced significant AhR activation on PND 6 but not on PND 14. The overproduction of prostaglandin E2 (PGE2), which is a pivotal mechanism in the development of neonatal hydronephrosis, was not observed, and no hydronephrosis was observed. These results suggested that the intense activation of AhR on PND 1 or 6 is insufficient to induce overproduction of PGE2 or hydronephrosis. Together with findings from previous studies, we conclude that the development of neonatal hydronephrosis depends on the duration and intensity of AhR activation.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 4","pages":"161-170"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772429","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 additional suitable positive controls in the human Cell Line Activation Test. 人类细胞系激活试验中其他合适阳性对照的研究。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.1

Kanako Nakayama, Shiho Oeda, Hideyuki Mizumachi, Morihiko Hirota, Akiko Tamura, Masaaki Miyazawa

{"title":"Investigation of additional suitable positive controls in the human Cell Line Activation Test.","authors":"Kanako Nakayama, Shiho Oeda, Hideyuki Mizumachi, Morihiko Hirota, Akiko Tamura, Masaaki Miyazawa","doi":"10.2131/jts.50.1","DOIUrl":"https://doi.org/10.2131/jts.50.1","url":null,"abstract":"The human Cell Line Activation Test (h-CLAT) is an in vitro skin sensitization assay adopted by the OECD as Test Guideline 442E. In the h-CLAT, 2,4-dinitrochlorobenzene (DNCB) is used as a positive control; however, DNCB is considered a poisonous substance under the Poisonous and Deleterious Substances Control Act in Japan since 2014 because of its high acute toxicity. Strict control, handling, and storage are required when using DNCB, which is a burden to the users. Although the use of other suitable positive controls with historical data is accepted by the guideline, to our knowledge, there have been no reports of such substances. Therefore, in this study, we investigated suitable positive controls that can be used in addition to DNCB for the h-CLAT. Three candidates that are not considered poisonous substances, imidazolidinyl urea, hydroxycitronellal, and 2,4-dinitrofluorobenzene, were selected. To determine their suitability as positive controls, the h-CLAT was performed repeatedly for each chemical in two laboratories. For imidazolidinyl urea, the results that failed the positive control criteria were observed in both laboratories, indicating that it was inconclusive for the suitability as a positive control at the tested concentration. In contrast, all experiments with hydroxycitronellal and 2,4-dinitrofluorobenzene met the criteria and resulted in relative fluorescence intensity values of CD86/CD54, which were comparable to those for DNCB. Based on these results, hydroxycitronellal and 2,4-dinitrofluorobenzene may be used as positive controls. This study would provide valuable information for users examining other suitable positive controls in the h-CLAT.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 1","pages":"1-9"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950774","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

The effects of anemia on the timing of pubertal onset in female rats. 贫血对雌性大鼠青春期开始时间的影响。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.83

Mariko Shimada, Yoshinori Hosokawa, Ryo Ihara, Keiko Ogata, Katsumasa Iwashita, Ryoko Matsuyama, Hiroyuki Asano

{"title":"The effects of anemia on the timing of pubertal onset in female rats.","authors":"Mariko Shimada, Yoshinori Hosokawa, Ryo Ihara, Keiko Ogata, Katsumasa Iwashita, Ryoko Matsuyama, Hiroyuki Asano","doi":"10.2131/jts.50.83","DOIUrl":"10.2131/jts.50.83","url":null,"abstract":"Attainment of vaginal patency is an endpoint for the onset of puberty in female animals in toxicity studies. It is widely acknowledged that certain substances with endocrine-modulating effects can influence the timing of puberty in female rats and that factors unrelated to endocrine mechanisms, such as malnutrition and stress, can also affect pubertal onset. Some epidemiological studies have also suggested a link between anemia and delay in pubertal onset in women, however, little is known regarding the relation between hematological changes and female pubertal onset in experimental animals. The purpose of this study was to examine the effects of anemia during the prepubertal period on pubertal onset and reproductive organs in female rats. In this study, anemia was induced by drawing a certain amount of blood from the jugular vein or by intraperitoneal administration of phenylhydrazine, a well-known inducer of hemolytic anemia. As a result, both treatment groups showed a transient anemia characterized by an approximately 20-35% decrease in hemoglobin levels compared to the control group. Anemia in these female rats produced no obvious changes in body weight on each postnatal day and had no effect on the weights and histopathology of reproductive organs after sexual differentiation, but the age at vaginal opening (VO) was delayed and the body weight at VO was higher than the same parameters in the control group. These results suggest that anemia in prepubertal females could cause a delay in pubertal onset.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 2","pages":"83-95"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080638","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

Pathophysiological interaction of dextran sodium sulfate-induced colitis and diet-induced hepatic lesions in mice. 右旋糖酐硫酸钠诱导小鼠结肠炎和饮食性肝损伤的病理生理相互作用。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.343

Kinuko Uno, Keita Sekiguchi, Noriko Suzuki-Kemuriyama, Takeshi Ohta, Katsuhiro Miyajima

{"title":"Pathophysiological interaction of dextran sodium sulfate-induced colitis and diet-induced hepatic lesions in mice.","authors":"Kinuko Uno, Keita Sekiguchi, Noriko Suzuki-Kemuriyama, Takeshi Ohta, Katsuhiro Miyajima","doi":"10.2131/jts.50.343","DOIUrl":"https://doi.org/10.2131/jts.50.343","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD) is a lifestyle-related disease. A gut-liver axis is involved in the progression of NAFLD. Disruption of the intestinal barrier function is an exacerbating factor of NAFLD. In this study, we have investigated the interaction between colitis and NAFLD in mouse models of dextran sodium sulfate (DSS)-induced colitis and diet-induced NAFLD-like lesions. Male C57BL/6J mice were provided with a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) and 1.25% DSS water for 3 weeks. The DSS water was administered intermittently. In the large intestine, the DSS-treated groups clearly demonstrated inflammation. Dilation of crypt and goblet cells was observed in the DSS + CDAHFD group. The expression of minor inflammation-related genes was increased in the CDAHFD group. In the liver, the CDAHFD group demonstrated non-alcoholic steatohepatitis (NASH)-like lesions. The number of C-X-C motif chemokine ligand 16 (CXCL16)-positive cells increased in the CDAHFD group and tended to increase in the DSS + CDAHFD group. Toll-like receptor 4 (TLR4)-positive cells were observed mainly in gallbladder epithelial cells in all groups and were more pronounced in the DSS-administered groups. Inflammation-related genes were upregulated in the DSS group. The expression of fibrosis-related genes increased in the DSS + CDAHFD group. DSS-induced colitis and CDAHFD-induced NASH interacted with each other. NAFLD lesions were induced by CDAHFD and exacerbated by TLR4 and CXCL16 in DSS-induced colitis. Colitis is induced by DSS and exacerbated by changes in the intestinal environment due to liver injury. This combined model was useful in analyzing early lesions of liver-gut axis for NAFLD.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 7","pages":"343-350"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553836","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