Journal of pharmacological sciences最新文献_第10页

SMTP-44D alleviates diabetic retinopathy by suppressing inflammation and oxidative stress in in vivo and in vitro models 在体内和体外模型中，SMTP-44D通过抑制炎症和氧化应激来缓解糖尿病视网膜病变。

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-02-01 DOI: 10.1016/j.jphs.2024.12.004

Mio Ishibashi , Keita Shibata , Michishige Terasaki , Yuta Saito , Sho-ichi Yamagishi , Keiji Hasumi , Koji Nobe

{"title":"SMTP-44D alleviates diabetic retinopathy by suppressing inflammation and oxidative stress in in vivo and in vitro models","authors":"Mio Ishibashi , Keita Shibata , Michishige Terasaki , Yuta Saito , Sho-ichi Yamagishi , Keiji Hasumi , Koji Nobe","doi":"10.1016/j.jphs.2024.12.004","DOIUrl":"10.1016/j.jphs.2024.12.004","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults, and inflammation and oxidative stress contribute to DR development. However, no effective treatments are currently approved for DR. Therefore, this study aimed to investigate the effects of SMTP-44D—a <em>Stachybotrys microspora-</em>derived compound with anti-inflammatory and antioxidant properties—on DR in <em>in vivo</em> and <em>in vitro</em> models. Diabetes was induced in rats using 60 mg/kg streptozocin, followed by treatment with SMTP-44D every second day. Retinal function was assessed using electroretinography every 2 months for 8 months. SMTP-44D prevented diabetes-induced b-wave amplitude reductions in electroretinogram and decreased retinal ganglion cell apoptosis. SMTP-44D also reduced the accumulation of advanced glycation end-products (AGEs), AGE receptors, and 8-hydroxydeoxyguanosine in the retina. Furthermore, when rat retinal Müller cells were cultured in DMEM medium containing 35 mM glucose (high glucose, HG) and treated with SMTP-44D for 24 h, SMTP-44D mitigated cell death, reactive oxygen species production, and inflammatory cytokine levels in the cells. These findings suggest that SMTP-44D exhibits significant antioxidant and anti-inflammatory effects, highlighting its potential as a therapeutic candidate for DR.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 2","pages":"Pages 57-64"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Neurotropin® alleviates nerve damage in a mouse chronic nerve compression model Neurotropin®减轻小鼠慢性神经压迫模型中的神经损伤。

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-02-01 DOI: 10.1016/j.jphs.2024.12.006

Toshiki Shimada , Toru Iwahashi , Koji Suzuki , Taisuke Kasuya , Yoshiaki Yoshimura , Katsuyuki Konishi , Atsushi Kamata , Mai konishi , Satoshi Miyamura , Ryoya Shiode , Arisa Kazui , Kunihiro Oka , Seiji Okada , Hiroyuki Tanaka

{"title":"Neurotropin® alleviates nerve damage in a mouse chronic nerve compression model","authors":"Toshiki Shimada , Toru Iwahashi , Koji Suzuki , Taisuke Kasuya , Yoshiaki Yoshimura , Katsuyuki Konishi , Atsushi Kamata , Mai konishi , Satoshi Miyamura , Ryoya Shiode , Arisa Kazui , Kunihiro Oka , Seiji Okada , Hiroyuki Tanaka","doi":"10.1016/j.jphs.2024.12.006","DOIUrl":"10.1016/j.jphs.2024.12.006","url":null,"abstract":"<div><div>Chronic nerve compression disorders, such as carpal tunnel syndrome, are common and can significantly impair daily activities due to motor and sensory dysfunctions. Currently, no systemic pharmacotherapy exists for preventing or treating disease progression. This study aims to investigate whether Neurotropin®, an established analgesic, has therapeutic effects. A chronic nerve compression model was created by wrapping a silicone tube around the sciatic nerve in C57BL/6 mice. Nerves were evaluated electrophysiologically and histologically 2 weeks post-surgery. To confirm the preventive effect on disease onset, we administered Neurotropin® subcutaneously. Additionally, continuous subcutaneous administration of Neurotropin® was started 2 weeks post-surgery, and the therapeutic effects were evaluated at 4 and 8 weeks. Furthermore, the therapeutic effects of daily oral administration of Neurotropin®, starting 2 weeks post-surgery, were evaluated at 8 weeks. Significant decreases in nerve conduction velocity and axonal myelination were observed at 2 weeks post-injury. Neurotropin® administration initiated concurrently with model creation did not prevent disease onset at 2 weeks post-surgery. However, starting administration of Neurotropin® 2 weeks post-injury significantly improved outcomes at 8 weeks post-surgery compared to the control group, with continuous subcutaneous and daily oral administration. Neurotropin® may exhibit therapeutic effects for chronic nerve compression disorders.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 2","pages":"Pages 88-95"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Cystine transporter SLC7A11 regulates sensitivity to unsaturated carbonyl compounds in mouse macrophage cell lines 胱氨酸转运体SLC7A11调节小鼠巨噬细胞对不饱和羰基化合物的敏感性。

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-02-01 DOI: 10.1016/j.jphs.2024.12.008

Tsunehito Higashi , Konoka Hashimoto , Yosuke Mai , Fumito Naganuma , Takeo Yoshikawa

{"title":"Cystine transporter SLC7A11 regulates sensitivity to unsaturated carbonyl compounds in mouse macrophage cell lines","authors":"Tsunehito Higashi , Konoka Hashimoto , Yosuke Mai , Fumito Naganuma , Takeo Yoshikawa","doi":"10.1016/j.jphs.2024.12.008","DOIUrl":"10.1016/j.jphs.2024.12.008","url":null,"abstract":"<div><div>Cytotoxic effects of cigarette smoke are thought to be causes of cigarette smoking-related diseases such as respiratory infection, chronic obstructive pulmonary disease, and atherosclerosis. Unsaturated carbonyl compounds are major cytotoxic factors in the gas phase of cigarette smoke. Cell death induced by unsaturated carbonyl compounds in cigarette smoke is PKC-dependent ferroptosis. Although the cell sensitivity to unsaturated carbonyl compounds varies by cell types, the molecular mechanisms underlying this sensitivity remain unclear. In this study, we have examined the factors involved in determining sensitivity to unsaturated carbonyl compounds. We found that two mouse macrophage cell lines exhibited different sensitivities; J774.1 macrophages were sensitive to unsaturated carbonyl compounds, whereas RAW264.7 macrophages were resistant. Glutathione synthesis inhibitor increased the sensitivity of RAW264.7 macrophages to unsaturated carbonyl compounds. Quantitative RT-PCR revealed that the expression level of the cystine transporter SLC7A11 was higher in RAW264.7 macrophages than in J774.1 macrophages. Inhibition of SLC7A11 activity increased sensitivity to unsaturated carbonyl compounds, while overexpression of SLC7A11 enhances resistance to these compounds. The current results suggest that the SLC7A11 level is a key factor in determining the macrophage sensitivity to unsaturated carbonyl compounds.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 2","pages":"Pages 96-103"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Effect of antidepressants and social defeat stress on the activity of dorsal raphe serotonin neurons in free-moving animals 抗抑郁药和社交失败压力对自由活动动物中叶背血清素神经元活动的影响。

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-02-01 DOI: 10.1016/j.jphs.2025.01.001

Masashi Koda , Hiroyuki Kawai , Hisashi Shirakawa , Shuji Kaneko , Kazuki Nagayasu

{"title":"Effect of antidepressants and social defeat stress on the activity of dorsal raphe serotonin neurons in free-moving animals","authors":"Masashi Koda , Hiroyuki Kawai , Hisashi Shirakawa , Shuji Kaneko , Kazuki Nagayasu","doi":"10.1016/j.jphs.2025.01.001","DOIUrl":"10.1016/j.jphs.2025.01.001","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is among the most common mental disorders worldwide and is characterized by dysregulated reward processing associated with anhedonia. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for MDD; however, their onset of action is delayed. Recent reports have shown that serotonin neurons in the dorsal raphe nucleus (DRN) are activated by rewards and play a vital role in reward processing. However, whether antidepressant treatment affects the DRN serotonin neuronal response to rewards in awake animals remains unknown. In this study, we measured the activity of DRN serotonin neurons in awake mice and determined the effects of antidepressants and chronic stress on DRN serotonin neuronal activity. We found that acute treatment with citalopram, an SSRI, significantly decreased sucrose-induced activation of DRN serotonin neurons. The decrease in response to acute citalopram treatment was attenuated by chronic citalopram treatment. Acute treatment with (<em>S</em>)-WAY100135, a 5-HT<sub>1A</sub> receptor antagonist, dose-dependently inhibited the response to acute citalopram treatment. These results indicate that autoinhibition by activating 5-HT<sub>1A</sub> receptors via acute SSRI treatment may blunt the reward response, which can be recovered after chronic SSRI treatment.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 2","pages":"Pages 113-123"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Targeting enteric glial CRF-R1/Cx43 attenuates stress-induced accelerated colonic motility 靶向肠胶质细胞CRF-R1/Cx43可减弱应激诱导的加速结肠运动

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-27 DOI: 10.1016/j.jphs.2025.01.009

Haiqing Chang , Haifeng Zhang , Shiqiu Jiang , Juan Hu , Hongli Ma , Bo Cheng , Qiang Wang , Yansong Li

{"title":"Targeting enteric glial CRF-R1/Cx43 attenuates stress-induced accelerated colonic motility","authors":"Haiqing Chang , Haifeng Zhang , Shiqiu Jiang , Juan Hu , Hongli Ma , Bo Cheng , Qiang Wang , Yansong Li","doi":"10.1016/j.jphs.2025.01.009","DOIUrl":"10.1016/j.jphs.2025.01.009","url":null,"abstract":"<div><div>Stress triggers disorders in accelerated peristalsis, with corticotropin releasing factor receptor 1 (CRF-R1) playing a pivotal role. Enteric glia cells (EGCs) and glial Cx43 are known to influence gastrointestinal motility, yet their involvement in colonic motor responses to stress remains unclear. Using immunofluorescence and single-cell RNA sequencing data, we identified CRF-R1 expression in EGCs. Male C57BL/6 mice subjected to wrap restraint stress (WRS) revealed stress-induced colonic motility changes. By employing Fluoroacetate, NBI 27914, and Gap26, we elucidated the impact of glial CRF-R1/Cx43 on stress-induced colonic motor responses. Our study demonstrated CRF-R1 expression in EGCs of the small intestine and colon, along with elevated CRF levels and upregulated CRF-R1 in the distal colon under stress. Antagonizing CRF-R1 and disrupting EGC function made mice resistant to colonic stress responses. Mechanistically, increased glial Cx43 expression and activity influenced colonic motor responses in a CRF-R1-dependent manner. Our findings highlight the role of EGC-derived CRF-R1 in stress-induced colonic motor responses via Cx43 activation. Targeting CRF-R1/Cx43 signaling in EGCs may offer a promising approach to mitigate stress-induced colonic transit changes.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 3","pages":"Pages 167-178"},"PeriodicalIF":3.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 fecal microbiota transplantation on behavioral abnormality in attention deficit hyperactivity disorder-like model rats 粪便菌群移植对注意缺陷多动障碍样模型大鼠行为异常的影响

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-27 DOI: 10.1016/j.jphs.2025.01.007

Wakana Harigai , Kanata Mikami , Mohammed E. Choudhury , Hiroto Yamauchi , Chisato Yajima , Shin Shimizu , Noriyuki Miyaue , Masahiro Nagai , Madoka Kubo , Junya Tanaka , Taiichi Katayama

{"title":"Effects of fecal microbiota transplantation on behavioral abnormality in attention deficit hyperactivity disorder-like model rats","authors":"Wakana Harigai , Kanata Mikami , Mohammed E. Choudhury , Hiroto Yamauchi , Chisato Yajima , Shin Shimizu , Noriyuki Miyaue , Masahiro Nagai , Madoka Kubo , Junya Tanaka , Taiichi Katayama","doi":"10.1016/j.jphs.2025.01.007","DOIUrl":"10.1016/j.jphs.2025.01.007","url":null,"abstract":"<div><div>Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. ADHD symptoms not only impact patients and their families but also impose societal costs. Current treatments for ADHD, including environmental adjustments and medication, are symptomatic and require long-term management. Recently, the link between gut microbiota dysbiosis and various psychiatric and neurological disorders has become evident. The effectiveness of fecal microbiota transplantation (FMT) from healthy individuals in treating autism spectrum disorder, a neurodevelopmental disorder related to ADHD, has been demonstrated. However, despite suggestions of a relationship between ADHD and gut microbiota, few studies have explored the efficacy of FMT for ADHD. In the current study, we used 16S rDNA analysis to show that ADHD-like model rats possess a gut microbiota that is distinct from that of healthy rats, and we demonstrated that FMT from healthy rats improved hyperactivity in ADHD-like model rats. Our findings suggest that differences in gut microbiota underlie ADHD-like behaviors and that FMT may be an effective treatment for ADHD.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 3","pages":"Pages 189-198"},"PeriodicalIF":3.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Asperuloside suppresses the progression of depression through O-GlcNAcylation of IκBα and regulating NFκB signaling Asperuloside通过i - κ b α的o - glcn酰化和调节NFκB信号传导抑制抑郁症的进展

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-24 DOI: 10.1016/j.jphs.2025.01.010

Li Yin , Huakun Wang , Hong Xu , Haixiao Lu , Jiayu Lv , Chengshu Lu

{"title":"Asperuloside suppresses the progression of depression through O-GlcNAcylation of IκBα and regulating NFκB signaling","authors":"Li Yin , Huakun Wang , Hong Xu , Haixiao Lu , Jiayu Lv , Chengshu Lu","doi":"10.1016/j.jphs.2025.01.010","DOIUrl":"10.1016/j.jphs.2025.01.010","url":null,"abstract":"<div><div>Depression is a pervasive mental disorder that poses a significant threat to human health globally. Asperuloside (ASP), an iridoid glycoside extracted from Herba Paederiae, exhibits a range of pharmacological activities, including anti-tumor and anti-inflammatory effects. This study aims to explore the function and molecular mechanisms of ASP in alleviating depression. Chronic unpredictable mild stress (CUMS) was employed to establish a rat model of depression. Behavioral tests were conducted to evaluate the antidepressant effects of ASP. Apoptosis in hippocampal tissues was assessed using TUNEL assay. Primary hippocampal neuron apoptosis was assessed using Annexin V/PI staining and flow cytometry, while cell death was detected via PI staining. The expression levels of target mRNAs and proteins were analyzed by quantitative PCR (qPCR) and western blotting, respectively. Additionally, the levels of O-GlcNAcylation and ubiquitination were determined by western blot analysis following immunoprecipitation. Molecular docking was performed to elucidate the interaction mode between ASP and its target protein, O-linked β-N-acetylglucosamine transferase (OGT). Our findings revealed that ASP treatment significantly ameliorated depression-like behaviors and cognitive dysfunction, as well as inhibited hippocampus apoptosis in CUMS-induced rats, Moreover, ASP inhibited LPS-induced neuronal cell apoptosis and suppressed the activation of the NF-κB signaling pathway. Mechanistically, we demonstrated that ASP promoted O-GlcNAcylation of IκBα, and suppressed its ubiquitination and phosphorylation, thereby stabilizing IκBα protein. In conclusion, ASP exerts antidepressant effects by enhancing IκBα O-GlcNAcylation, thus inhibiting its ubiquitination and phosphorylation. These findings provide a novel therapeutic target for the treatment of depression.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 3","pages":"Pages 179-188"},"PeriodicalIF":3.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Antidepressant effect of globin digest through enhanced hippocampal neurogenesis in a mouse model of lipopolysaccharide-induced depression 在脂多糖诱导的抑郁症小鼠模型中，珠蛋白消化通过增强海马神经发生的抗抑郁作用

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-23 DOI: 10.1016/j.jphs.2025.01.008

Osamu Nakagawasai , Kotaro Yamada , Kohei Takahashi , Fuka Niinuma , Wataru Nemoto , Koichi Tan-No

引用次数: 0

Alteration of COX-1 and TLR4 expression in the mouse brain during chronic social defeat stress revealed by Positron Emission Tomography study 正电子发射断层扫描研究慢性社会失败应激小鼠脑内COX-1和TLR4表达的变化

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-16 DOI: 10.1016/j.jphs.2025.01.006

Yumika Motooka , Ryota Shinohara , Shiho Kitaoka , Ai Uryu , Dongrui Li , Hiroyuki Neyama , Yilong Cui , Tatsuya Kida , Wakiko Arakaki , Hisashi Doi , Yasuyoshi Watanabe , Tomoyuki Furuyashiki

{"title":"Alteration of COX-1 and TLR4 expression in the mouse brain during chronic social defeat stress revealed by Positron Emission Tomography study","authors":"Yumika Motooka , Ryota Shinohara , Shiho Kitaoka , Ai Uryu , Dongrui Li , Hiroyuki Neyama , Yilong Cui , Tatsuya Kida , Wakiko Arakaki , Hisashi Doi , Yasuyoshi Watanabe , Tomoyuki Furuyashiki","doi":"10.1016/j.jphs.2025.01.006","DOIUrl":"10.1016/j.jphs.2025.01.006","url":null,"abstract":"<div><div>Despite the recognized roles of neuroinflammation in mental illnesses, PET imaging on currently available biomarkers has limitations due to the lack of evidence demonstrating their relationship to the molecular and cellular events of inflammation associated with the pathology of mental illness. Rodent stress models, such as chronic social defeat stress (SDS), have identified crucial roles for COX-1 and TLR4, which are innate immune molecules, in chronic SDS-induced neuroinflammation and its behavioral consequences. In this study, we performed COX-1 and TLR4 PET imaging at multiple time points during chronic SDS in mice. For COX-1 PET imaging, we used the COX-1 PET probe <em>(S)</em>-[<sup>18</sup>F]KTP-Me. Subchronic SDS transiently increased uptake and slower washout in broad regions of the brain, including the cerebral cortex, hippocampus, striatum, and thalamus. For TLR4 PET imaging, we developed a new BBB-permeable PET probe, [<sup>11</sup>C]<strong>1</strong>, which detected LPS-induced neuroinflammation. Washout of [<sup>11</sup>C]<strong>1</strong> was facilitated in the cerebellum after subchronic and chronic SDS and in the pons-medulla after chronic SDS. Collectively, our findings suggest the potential usefulness of COX-1 and TLR4 PET imaging in visualizing and understanding time-dependent process of neuroinflammation in stress-related mental illnesses.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 3","pages":"Pages 156-166"},"PeriodicalIF":3.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Darbepoetin alfa enhances exercise performance in trained mice in a sex-specific manner Darbepoetin α以性别特异性的方式增强训练小鼠的运动表现

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-10 DOI: 10.1016/j.jphs.2025.01.005

Yoshinori Iba , Shinichi Sawada , Yukika Yamada , Hiroki Murai , Yoshiyuki Ishida , Daisuke Nakata , Keiji Terao

{"title":"Darbepoetin alfa enhances exercise performance in trained mice in a sex-specific manner","authors":"Yoshinori Iba , Shinichi Sawada , Yukika Yamada , Hiroki Murai , Yoshiyuki Ishida , Daisuke Nakata , Keiji Terao","doi":"10.1016/j.jphs.2025.01.005","DOIUrl":"10.1016/j.jphs.2025.01.005","url":null,"abstract":"<div><div>Erythropoiesis-stimulating agents (ESAs) increase hemoglobin mass and maximal oxygen uptake; however, it remains unclear whether the abuse of ESAs enhances exercise performance. Therefore, we herein investigated the effects of darbepoetin alfa (DPO), a long-acting erythropoietin analog, on exercise performance in trained male and female mice. Exercise performance was assessed as the number of arrivals at the halfway line of a flow rate-adjustable swimming pool. The DPO treatment significantly increased hematocrit levels regardless of sex, but only enhanced exercise performance in female mice. The sex-specific effect of DPO on exercise performance was not abolished by ovariectomy; the enhancing effect was more pronounced in ovariectomized (OVX) mice than in female mice. This effect of the DPO treatment was attributed to a significant increase in the gene expression of PGC-1alpha in the gastrocnemius (GASTR) muscle of OVX mice, but not female mice. In addition, myocyte hypertrophy, but not angiogenesis, was observed in the GASTR muscle of DPO-treated OVX mice. These results revealed the sex-specific enhancing effect of DPO on exercise performance in trained mice. Enhanced exercise performance did not appear to require female sex hormones and may not be due to direct effects on skeletal muscles.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 3","pages":"Pages 131-138"},"PeriodicalIF":3.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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