Canadian journal of physiology and pharmacology最新文献_第2页

Coenzyme Q10 ameliorates hepatoprotective effect of metformin in experimentally-induced type 2 diabetes mellitus in rats: a functional and histological study. 辅酶Q10改善二甲双胍对实验性2型糖尿病大鼠的肝保护作用：一项功能和组织学研究

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0244

Heba Rady Salem, Asmaa Eldesouky, Mohamed S Amer, Doaa Z M Shebl, Eman S El-Roghy

{"title":"Coenzyme Q10 ameliorates hepatoprotective effect of metformin in experimentally-induced type 2 diabetes mellitus in rats: a functional and histological study.","authors":"Heba Rady Salem, Asmaa Eldesouky, Mohamed S Amer, Doaa Z M Shebl, Eman S El-Roghy","doi":"10.1139/cjpp-2025-0244","DOIUrl":"10.1139/cjpp-2025-0244","url":null,"abstract":"Management of metabolic dysfunction-associated steatotic liver disease (MASLD) remains a significant clinical challenge. This study evaluated the efficacy of Coenzyme Q10 (CoQ10) as an adjuvant therapy to metformin in the treatment of MASLD using an experimentally induced type 2 diabetes (T2D) rat model. T2D was induced in 18 rats through a high-fat diet combined with a low dose of streptozotocin. The diabetic rats were then randomly allocated into three equal groups: untreated, metformin-treated, and metformin/CoQ10-treated. An additional six rats maintained on a normal chow diet served as the control group. Development of MASLD was confirmed through biochemical assays and histopathological analyses. Liver histology and electron microscopy were performed, along with immunohistochemistry for BAX and CD68 markers. Our results demonstrated that T2D rats exhibited impaired glucose and lipid profiles, elevated liver enzymes, and reduced adiponectin levels. These alterations were accompanied by hepatic oxidative stress, histopathological features of MASLD, fibrosis, and increased expression of BAX and CD68. Treatment with either metformin monotherapy or metformin/CoQ10 combination therapy significantly ameliorated the biochemical and histopathological manifestations of MASLD, as well as reduced the expression of BAX and CD68 in the liver. Importantly, combined metformin/CoQ10 therapy exerted a stronger hepatoprotective effect than metformin alone.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-15"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017545","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

GLP-1 and diabetic nephropathy share key molecular targets. GLP-1与糖尿病肾病共享关键分子靶点。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0146

Wanderson Gabriel Gomes de Melo, Regina Lúcia Dos Santos Silva, Ianahanna Duarte Santos Soares, Bruno de Sousa Barbosa, Felipe Cardoso de Brito, Napoleão Martins Argôlo Neto, Dayseanny de Oliveira Bezerra

{"title":"GLP-1 and diabetic nephropathy share key molecular targets.","authors":"Wanderson Gabriel Gomes de Melo, Regina Lúcia Dos Santos Silva, Ianahanna Duarte Santos Soares, Bruno de Sousa Barbosa, Felipe Cardoso de Brito, Napoleão Martins Argôlo Neto, Dayseanny de Oliveira Bezerra","doi":"10.1139/cjpp-2025-0146","DOIUrl":"10.1139/cjpp-2025-0146","url":null,"abstract":"Glucagon-like peptide-1 (GLP-1) receptor agonists provide renoprotective benefits in diabetes, yet the molecular mechanisms linking GLP-1 signaling to diabetic nephropathy remain poorly defined. This study aimed to identify shared molecular targets between GLP-1 activity and diabetic kidney disease by integrating protein targets of GLP-1 from UniProt with disease-associated genes from GeneCards. The overlapping gene set was analyzed using STRING and Cytoscape® with MCODE clustering, followed by GO and KEGG enrichment through the clusterProfiler package. Molecular docking with HADDOCK was employed to validate structural interactions between GLP-1 and central network proteins. We identified 17 shared genes, including STAT3, EP300, MAPK1, and INSR, which formed a densely connected cluster enriched in pathways related to insulin response, hypoxia adaptation, apoptosis, and glucose metabolism. Docking analysis demonstrated direct and favorable binding of GLP-1 to STAT3, PIK3R1, and EP300, suggesting noncanonical intracellular mechanisms involving transcriptional regulation and epigenetic modulation. These findings reveal a novel convergence between GLP-1 signaling and diabetic nephropathy pathways, providing mechanistic insights that guide the experimental determination of the underlying molecular interactions. This framework may ultimately contribute to the refinement of renal therapies based on GLP-1 modulation.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-10"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146060043","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

Protective effects of Melissa officinalis ethanolic extract on doxorubicin-induced cardiotoxicity in a rat model. 梅莉莎乙醇提取物对阿霉素致大鼠心脏毒性的保护作用。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0217

Jelena N Terzic, Lazar Z Veljkovic, Vladimir L J Jakovljevic, Jovana N Novakovic, Jasmina Z Sretenovic, Maja D Muric, Aleksandar G Kocovic, Isidora M Milosavljevic

{"title":"Protective effects of Melissa officinalis ethanolic extract on doxorubicin-induced cardiotoxicity in a rat model.","authors":"Jelena N Terzic, Lazar Z Veljkovic, Vladimir L J Jakovljevic, Jovana N Novakovic, Jasmina Z Sretenovic, Maja D Muric, Aleksandar G Kocovic, Isidora M Milosavljevic","doi":"10.1139/cjpp-2025-0217","DOIUrl":"10.1139/cjpp-2025-0217","url":null,"abstract":"Despite its proven efficacy in cancer treatment, doxorubicin's therapeutic potential is limited by cumulative, dose-dependent cardiotoxicity, primarily associated with oxidative stress. Given the well-documented antioxidant properties of Melissa officinalis L., this study aimed to assess the cardioprotective potential of its ethanolic extract (MOE) against doxorubicin-induced cardiotoxicity (DIC). Twenty-one female Wistar albino rats were randomly divided into three groups: CTRL (healthy, untreated), DOX (doxorubicin-treated), and DOX-MO (treated with both doxorubicin and MOE). Doxorubicin (15 mg/kg, i.p.) was administered on Day 7, while MOE (200 mg/kg, orally) was given daily for 10 days. Cardiac function was evaluated using echocardiography and Langendorff-perfused hearts, followed by analysis of oxidative stress markers and morphometric analysis. MOE improved cardiac function and partially preserved myocardial architecture following DIC, significantly reducing fibrosis compared to the DOX group. Nitrite levels were significantly elevated in MOE-treated rats, suggesting preserved endothelial function and enhanced nitric oxide-mediated vasodilation. These results suggest that MOE may mitigate DIC through antioxidative and vasodilatory mechanisms, as well as by preserving endothelial and myocardial integrity. Histological findings further indicate a possible reduction in inflammatory changes, supporting a modest anti-inflammatory effect. These findings suggest that MOE may have cardioprotective potential against DIC, warranting further investigation in preclinical and clinical settings.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-14"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780135","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

Editorial Expression of Concern: Metformin attenuates ischemia/reperfusion-induced apoptosis of cardiac cells by downregulation of p53/microRNA-34a via activation of SIRT1. 编辑表达关注：二甲双胍通过激活SIRT1下调p53/microRNA-34a，从而减轻缺血/再灌注诱导的心肌细胞凋亡。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0060

Weiwei Li, Sheng Jin, Jie Hao, Yun Shi, Wenjie Li, Lingling Jiang

引用次数: 0

Sex-specific vascular effects of menthol: TRPM8- and TRPA1-dependent relaxation in female mouse aorta and pudendal arteries. 薄荷醇对雌性小鼠主动脉和阴部动脉TRPM8和trpa1依赖性松弛的性别特异性血管效应。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0101

Fênix Alexandra Araujo, Raiana Anjos Moraes, Rinaldo Rodrigues Dos Passos, Milene Tavares Fontes, Camilla Ferreira Wenceslau, R Clinton Webb, Fernanda Priviero, Cameron G McCarthy, Darízy Flávia Silva

{"title":"Sex-specific vascular effects of menthol: TRPM8- and TRPA1-dependent relaxation in female mouse aorta and pudendal arteries.","authors":"Fênix Alexandra Araujo, Raiana Anjos Moraes, Rinaldo Rodrigues Dos Passos, Milene Tavares Fontes, Camilla Ferreira Wenceslau, R Clinton Webb, Fernanda Priviero, Cameron G McCarthy, Darízy Flávia Silva","doi":"10.1139/cjpp-2025-0101","DOIUrl":"10.1139/cjpp-2025-0101","url":null,"abstract":"Sexual dysfunction affects the quality of life for both men and women. Menthol, a TRPM8 agonist, is widely used in products to enhance sexual performance due to its cooling effect. Beyond this, menthol also induces vascular effects in male arteries. To explore its effects on female vasculature, we studied male and female C57BL/6 mice, along with female TRPM8 knockout (KO) mice. We isolated the internal pudendal artery and aorta to assess isometric contractile force. Menthol-induced relaxation of the pudendal artery was reduced in both female TRPM8 KO and male mice compared to female controls. Acetylcholine-induced relaxation was not affected in females, but in males, it was attenuated by menthol and enhanced by M8-B, a TRPM8 inhibitor. Menthol did not alter responses to norepinephrine, serotonin, or histamine in either sex. Notably, menthol-induced relaxation was also reduced in the aortas of female TRPM8 KO mice. In both the aorta and pudendal arteries of female mice, the TRPA1 inhibitor HC030031 significantly diminished menthol-induced relaxation. These findings suggest that TRPM8 modulation plays a role in acetylcholine-induced relaxation in male, but not female, pudendal arteries. Moreover, the menthol vascular effect in female arteries relies on TRPM8 and TRPA1 activation.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-11"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917077","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

Sixty-minute inhalation of molecular hydrogen decreases blood oxygen saturation but does not alter autonomic cardiac regulation at rest in healthy females: a randomized, double-blind, placebo-controlled crossover study. 一项随机、双盲、安慰剂对照的交叉研究：吸入60分钟氢分子可降低健康女性静息时血氧饱和度，但不改变心脏自主调节。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0228

Pavel Grepl, Jakub Krejčí, Andrew McKune, Michal Botek

{"title":"Sixty-minute inhalation of molecular hydrogen decreases blood oxygen saturation but does not alter autonomic cardiac regulation at rest in healthy females: a randomized, double-blind, placebo-controlled crossover study.","authors":"Pavel Grepl, Jakub Krejčí, Andrew McKune, Michal Botek","doi":"10.1139/cjpp-2025-0228","DOIUrl":"10.1139/cjpp-2025-0228","url":null,"abstract":"Molecular hydrogen has gained attention for its potential antioxidant, anti-inflammatory, and ergogenic effects. However, its impact on blood oxygen saturation and autonomic cardiac regulation under resting conditions remains unclear. This randomized, double-blind, placebo-controlled crossover study investigated the effects of a 60 min molecular hydrogen inhalation on oxygen saturation and heart rate variability in healthy females. Twenty physically active participants (22.1 ± 1.6 years) completed two inhalation sessions with either molecular hydrogen or placebo (ambient air), separated by a 7-day washout period. Oxygen saturation and heart rate variability were continuously monitored during the 60 min of inhalation. The results using 60 min averages showed a statistically significant (p ≤ 0.007) decrease in oxygen saturation during molecular hydrogen inhalation (95.9 ± 1.0%) compared to placebo (96.7 ± 0.7%), but this decrease should not be considered clinically significant. No significant changes (all p ≥ 0.32) were observed in time-domain or frequency-domain heart rate variability indices. These findings suggest that, under resting conditions, molecular hydrogen inhalation does not induce functional changes in autonomic cardiac regulation, and the observed reduction in blood oxygen saturation does not compromise homeostatic stability.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-9"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767269","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

5 weeks of online resistance training with blood flow restriction increases sit-to-stand oxygen consumption in healthy older adults. 5周限制血流的在线阻力训练可以增加健康老年人坐立变耗氧量。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0270

Daniela Presta, Andreas Bergdahl

引用次数: 0

Current clinical application of incretin therapy for obesity management. 肠促胰岛素治疗肥胖症的临床应用现状。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0152

Karlie Skinner, Jennifer N Clements

引用次数: 0

Incretin therapy and obesity: current and future pharmacologic possibilities. 肠促胰岛素治疗和肥胖：现在和未来的药理学可能性。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0151

Emory Moss, Kennedy Hawk, Kathrine Lollis, Jennifer N Clements

引用次数: 0

Effect of slow-release hydrogen sulfide donor GYY4137 on vascular smooth muscle and endothelial response in an in vitro ischemia-reperfusion model of rat thoracic aorta. 缓释硫化氢供体GYY4137对体外大鼠胸主动脉缺血再灌注模型血管平滑肌及内皮反应的影响

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 Epub Date: 2025-12-19 DOI: 10.1139/cjpp-2025-0168

Ariyan Teimoori, Halit Güner Orhan, Nargiz Zeynalova, Elif Demirtaş, Oğuzhan Ekin Efe, Huriye Eda Özturan Özer, Selda Emre Aydıngöz

{"title":"Effect of slow-release hydrogen sulfide donor GYY4137 on vascular smooth muscle and endothelial response in an in vitro ischemia-reperfusion model of rat thoracic aorta.","authors":"Ariyan Teimoori, Halit Güner Orhan, Nargiz Zeynalova, Elif Demirtaş, Oğuzhan Ekin Efe, Huriye Eda Özturan Özer, Selda Emre Aydıngöz","doi":"10.1139/cjpp-2025-0168","DOIUrl":"10.1139/cjpp-2025-0168","url":null,"abstract":"Ischemia-reperfusion (IR) injury of vascular grafts used in coronary artery bypass surgery can compromise outcomes. This study examined whether GYY4137, a slow-release hydrogen sulfide donor, protects against IR-induced vascular damage in rat thoracic aorta. Twenty male Sprague-Dawley rats (21-22 months old) were randomly assigned to Control, IR, IR + GYY4137 (100 µM), and IR + GYY4137 (300 µM) groups. To induce IR injury, aortic rings were incubated in nitrogen-gassed saline at 4 °C for 24 h, then exposed to sodium hypochlorite (200 µM) at 37 °C for 30 min. Vascular function was evaluated in organ baths; malondialdehyde, glutathione, and caspase-3 were quantified. IR injury markedly impaired contraction and endothelium-dependent relaxation, which GYY4137 did not restore. In contrast, IR increased malondialdehyde (p = 0.02), which fell to near-control with both 100 µM (p = 0.008) and 300 µM GYY4137 (p = 0.012). IR lowered glutathione (p = 0.012) was restored by 300 µM GYY4137 (p = 0.004). Likewise, caspase-3 rose (p = 0.02) but returned to near-control with both 100 µM (p = 0.004) and 300 µM GYY4137 (p = 0.02). In conclusion, GYY4137 reduces oxidative stress and apoptosis markers without improving vascular dysfunction in an IR model of rat thoracic aorta. This disparity underscores the complex pathophysiology of vascular IR injury, where cellular-level protection does not readily translate to functional recovery.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-10"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343714","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