Canadian journal of physiology and pharmacology最新文献

Exploring the supraspinal antihyperalgesic effects of levetiracetam in the rat model of chronic constriction injury. 探讨左乙拉西坦对大鼠慢性缩窄性损伤的脊髓上抗痛觉作用。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-07-01 Epub Date: 2025-04-17 DOI: 10.1139/cjpp-2024-0302

Feyza Alyu Altinok, Michele Petrella, Alessio Masi, Anna Maria Borruto, Roberto Ciccocioppo, Yusuf Ozturk

{"title":"Exploring the supraspinal antihyperalgesic effects of levetiracetam in the rat model of chronic constriction injury.","authors":"Feyza Alyu Altinok, Michele Petrella, Alessio Masi, Anna Maria Borruto, Roberto Ciccocioppo, Yusuf Ozturk","doi":"10.1139/cjpp-2024-0302","DOIUrl":"10.1139/cjpp-2024-0302","url":null,"abstract":"Neuropathic pain severely impacts quality of life and effective treatments are needed. To address this, the present study investigated the antihyperalgesic mechanisms of levetiracetam administered at the supraspinal level, together with its effects on ion channel activities. The ventral posterolateral nucleus of the thalamus was selected as the location for micro-injection. Thermal hyperalgesia and mechanical allodynia were assessed via in vivo experiments using the Hargreave's and e-Von Frey apparatus, respectively. Levetiracetam displayed statistically meaningful time and dose-dependent effects in the chronic constriction injury model, with statistical probability values less than 0.05. It was discovered that the antihyperalgesic effects were more pronounced in mechanical allodynia. Electrophysiological studies conducted through whole-cell patch clamp recordings indicated that levetiracetam tended to activate or increase the permeability of one or more channels for ion flow that are active only at hyperpolarized membrane potentials (-130 to -90 mV), suggesting the potential participation of hyperpolarization-activated cyclic nucleotide-gated, inwardly-rectifying K+, or G protein-gated inwardly-rectifying K+ channels. The findings could guide future drug development studies towards levetiracetam and its derivatives as effective treatments for neuropathic pain.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"244-256"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954898","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

Polygenic scores of obesity in childhood based on summary statistics from adults versus children. 儿童肥胖的多基因评分基于成人与儿童的汇总统计。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-07-01 Epub Date: 2025-03-25 DOI: 10.1139/cjpp-2024-0221

Danick Goulet, Michel Boivin, Christopher Gravel, Julian Little, Isabelle Ouellet-Morin, Jean-Philippe Gouin, Lise Dubois

{"title":"Polygenic scores of obesity in childhood based on summary statistics from adults versus children.","authors":"Danick Goulet, Michel Boivin, Christopher Gravel, Julian Little, Isabelle Ouellet-Morin, Jean-Philippe Gouin, Lise Dubois","doi":"10.1139/cjpp-2024-0221","DOIUrl":"10.1139/cjpp-2024-0221","url":null,"abstract":"The lack of polygenic scores (PGSs) developed for body mass index (BMI) in children may be problematic because the genetic architecture characterizing BMI changes throughout life. This study aims to describe the genetic susceptibility to obesity in children and to compare two PGSs based on data from adults and children and their association with BMI and discrimination of obesity. The study sample comprises 717 participants aged 4-13 years. Adult- and child-based PGSs were evaluated by examining (1) mean BMI across polygenic score risk categories, (2) the capacity to identify obesity with logistic regression, and (3) the linear association with BMI z-scores using linear regression. Increases in one standardized unit of adult-based PGS were related to a stronger increase in BMI z-score (β = 0.24-0.39) than PGS derived in children (β = 0.21-0.30). The association between obesity and the child score was higher (OR = 1.75-2.33) than that for the adult score (OR = 1.74-2.06) for the age group 4-7 years. The inverse was observed for the age group 8-13 years (ORchild 1.56-1.79 vs. ORadult 1.78-2.54). Both adult- and child-based PGSs show strong associations with BMI and risk of obesity, with the adult-based score standing out from 8 years old.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"225-235"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708705","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

Nampt: a new therapeutic target for modulating NAD⁺ levels in metabolic, cardiovascular, and neurodegenerative diseases. Nampt：在代谢、心血管和神经退行性疾病中调节NAD+水平的新治疗靶点

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-07-01 Epub Date: 2025-04-09 DOI: 10.1139/cjpp-2024-0400

Ravikumar Manickam, Sandhya Santhana, Wanling Xuan, Kirpal S Bisht, Srinivas M Tipparaju

{"title":"Nampt: a new therapeutic target for modulating NAD+ levels in metabolic, cardiovascular, and neurodegenerative diseases.","authors":"Ravikumar Manickam, Sandhya Santhana, Wanling Xuan, Kirpal S Bisht, Srinivas M Tipparaju","doi":"10.1139/cjpp-2024-0400","DOIUrl":"10.1139/cjpp-2024-0400","url":null,"abstract":"NAD+ is an important cofactor involved in regulating many biochemical processes in cells. An imbalance in NAD+/NADH ratio is linked to many diseases. NAD+ is depleted in diabetes, cardiovascular and neurodegenerative diseases, and in aging, and is increased in tumor cells. NAD+ is generated in cells via the de novo, Preiss-Handler, and salvage pathways. Most of the cellular NAD+ is generated through Nampt activation, a key rate-limiting enzyme that is involved in the salvage pathway. Restoration of NAD+/NADH balance offers therapeutic advantages for improving tissue homeostasis and function. NAD+ is known to benefit and restore the body's physiological mechanisms, including DNA replication, chromatin and epigenetic modifications, and gene expression. Recent studies elucidate the role of NAD+ in cells utilizing transgenic mouse models. Translational new therapeutics are positioned to utilize the NAD+ restoration strategies for overcoming the drawbacks that exist in the pharmacological toolkit. The present review highlights the significance of Nampt-NAD+ axis as a major player in energy metabolism and provides an overview with insights into future strategies, providing pharmacological advantages to address current and future medical needs.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"208-224"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954602","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

Naringin prevents the impairment of hepatic mitochondrial function in diabetic rats. 柚皮苷对糖尿病大鼠肝线粒体功能损害的预防作用。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-07-01 Epub Date: 2025-04-25 DOI: 10.1139/cjpp-2024-0357

María A Rizzi, Adriana Pérez, Solange Guizzardi, Nori Tolosa de Talamoni, Valeria A Rodríguez

{"title":"Naringin prevents the impairment of hepatic mitochondrial function in diabetic rats.","authors":"María A Rizzi, Adriana Pérez, Solange Guizzardi, Nori Tolosa de Talamoni, Valeria A Rodríguez","doi":"10.1139/cjpp-2024-0357","DOIUrl":"10.1139/cjpp-2024-0357","url":null,"abstract":"We previously demonstrated that naringin (NAR) protects against liver damage in streptozotocin (STZ)-induced diabetes in rats. The aim of this study was to elucidate whether NAR is also able to protect the functioning, biogenesis and dynamics of the liver mitochondria in diabetic rats (DM). The activities of isocitrate dehydrogenase and malate dehydrogenase from the Krebs cycle, complex I-III from electron chain and adenosine triphosphate synthase were decreased in DM rats, effects that were blocked by NAR. The gene expression of mitofusin-2 and GTPase dynamin-related protein 1, markers of mitochondrial fusion and fission, were decreased in DM rats, which was prevented by NAR. Total glutathione was decreased and protein carbonyl contents as well as the activity of the antioxidant enzymes were increased in DM rats. All these changes were blocked by NAR. In conclusion, NAR protects the liver mitochondria from DM rats avoiding changes in the activity of Krebs cycle, the respiratory chain and the oxidative phosphorylation as well as preventing alterations in the fusion-fission processes. These effects are mediated, at least in part, by decreasing oxidative stress and anomalies in the enzymatic antioxidant system. Further studies are necessary to validate efficacy and safety of NAR for human use.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"236-243"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973221","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

Repurposing incretin therapies: a narrative review of emerging indications across cardiometabolic, liver, kidney, neurological, psychiatric, and other systems. 肠促胰岛素治疗的重新定位：对心脏代谢、肝脏、肾脏、神经、精神和其他系统的新适应症的叙述性回顾。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-05-14 DOI: 10.1139/cjpp-2025-0038

Ibrahim S Alhomoud, Sarah E Wheeler, Dave L Dixon

引用次数: 0

Epigenetic regulation by ketone bodies in cardiac diseases and repair. 酮体在心脏疾病及其修复中的表观遗传调控。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-05-07 DOI: 10.1139/cjpp-2024-0270

Narasimman Gurusamy, Bandar Muteb H Almalki, Sai Katragadda, James Murray, Robert C Speth, Lisa S Robison

{"title":"Epigenetic regulation by ketone bodies in cardiac diseases and repair.","authors":"Narasimman Gurusamy, Bandar Muteb H Almalki, Sai Katragadda, James Murray, Robert C Speth, Lisa S Robison","doi":"10.1139/cjpp-2024-0270","DOIUrl":"10.1139/cjpp-2024-0270","url":null,"abstract":"Ketone bodies, particularly β-hydroxybutyrate (BHB), play an important role in the epigenetic regulation of gene expression in cardiac tissues, impacting both cardiac health and disease. This review explores the multifaceted influence of ketone bodies on epigenetic mechanisms, including histone acetylation, DNA methylation, ubiquitination, sirtuins activation, and RNA modulation. By acting as endogenous histone deacetylase inhibitors, ketone bodies enhance histone acetylation, thereby promoting the expression of genes involved in antioxidant defenses, anti-inflammatory responses, and metabolic regulation. Furthermore, BHB affects DNA methylation patterns by altering the availability of key metabolites such as S-adenosylmethionine. Ketogenic diet, which elevates BHB levels, has been shown to modulate gene expression, such as increasing FOXO3a and metallothionein 2, and improve cardiac function. This review highlights the therapeutic potential of ketone bodies in managing cardiac diseases through their epigenetic effects, underscoring the need for further research to elucidate the detailed molecular pathways and long-term impacts of these metabolic interventions.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959472","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

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-05-06 DOI: 10.1139/cjpp-2025-0039

Ning Dai, Jody Groenendyk, Marek Michalak

引用次数: 0

Examining tissue-level changes in doxorubicin accumulation and nitric oxide formation in skeletal muscle and tumours in a mouse model of breast cancer. 在乳腺癌小鼠模型中检测骨骼肌和肿瘤中阿霉素积累和一氧化氮形成的组织水平变化。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-05-01 Epub Date: 2025-02-25 DOI: 10.1139/cjpp-2024-0368

Meghan V McCue, Irena A Rebalka, Thomas J Hawke, David A MacLean

{"title":"Examining tissue-level changes in doxorubicin accumulation and nitric oxide formation in skeletal muscle and tumours in a mouse model of breast cancer.","authors":"Meghan V McCue, Irena A Rebalka, Thomas J Hawke, David A MacLean","doi":"10.1139/cjpp-2024-0368","DOIUrl":"10.1139/cjpp-2024-0368","url":null,"abstract":"Doxorubicin is a commonly used chemotherapy that rapidly accumulates in skeletal muscle and disrupts nitric oxide (NO) formation. However, studies investigating these effects have largely been performed in tumour-free models, therefore it remains unknown whether intramuscular accumulation and disruptions to NO content persist during tumour growth. Female C57bl/6 mice (n = 8/group) were randomly assigned to true control, doxorubicin control, tumour only, or tumour plus doxorubicin groups. Tumours were grown for 21, 24, or 28 days using E0771 cells. Doxorubicin was administered as a single 10 mg/kg intraperitoneal dose on day 21. Doxorubicin accumulation was similar in muscle with and without tumours present. Doxorubicinol, a metabolite of doxorubicin, was elevated (p < 0.05) in 24-day tumour + doxorubicin compared to doxorubicin alone. NO was similar across all groups in muscle; however, tumour NO was 15-fold higher at day 21 compared to 24, or 28 days (p < 0.05). The results confirm that doxorubicin is sequestered in skeletal muscle when a tumour is present, which may impact bioavailability. Tumour growth transiently increased intramuscular doxorubicinol, potentially exacerbating the toxicity of the drug. Earlier stage tumour growth appeared to profoundly elevate NO, which could suggest temporal angiogenesis and vasodilation to facilitate growth.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"163-171"},"PeriodicalIF":1.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499321","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

Systematic review of Health Canada approved clinical therapeutic trials for the treatment or prevention of coronavirus disease 2019 (COVID-19). 加拿大卫生部批准的2019年治疗或预防冠状病毒病（COVID-19）临床治疗试验的系统评价

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-05-01 Epub Date: 2025-03-06 DOI: 10.1139/cjpp-2024-0055

Antonios M Diab, Hailey M Stack, Brendan T McKeown, Bruce C Carleton, Kerry B Goralski

引用次数: 0

Vitamin C protects against doxorubicin-induced skeletal muscle atrophy: role of oxidative stress. 维生素C防止阿霉素引起的骨骼肌萎缩：氧化应激的作用。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-05-01 Epub Date: 2025-02-12 DOI: 10.1139/cjpp-2024-0154

Antonio Viana do Nascimento Filho, Gauri Akolkar, Lara Susan Lima, Filipe Fernandes Stoyell-Conti, Nathalia Bernardes, Maria Claudia Irigoyen, Pawan K Singal, Kátia De Angelis, Danielle da Silva Dias

{"title":"Vitamin C protects against doxorubicin-induced skeletal muscle atrophy: role of oxidative stress.","authors":"Antonio Viana do Nascimento Filho, Gauri Akolkar, Lara Susan Lima, Filipe Fernandes Stoyell-Conti, Nathalia Bernardes, Maria Claudia Irigoyen, Pawan K Singal, Kátia De Angelis, Danielle da Silva Dias","doi":"10.1139/cjpp-2024-0154","DOIUrl":"10.1139/cjpp-2024-0154","url":null,"abstract":"Doxorubicin is known for its significant cardiotoxicity, in part due to increased oxidative stress (OS). In addition, preclinical models have shown that doxorubicin induces skeletal muscle atrophy. While vitamin C has been recognized as a valuable pharmacological intervention to mitigate cardiac toxicity, its effect on doxorubicin-induced skeletal muscle atrophy remains to be determined. Therefore, the aim of this study was to investigate the effects of vitamin C on skeletal muscle of rats exposed to doxorubicin. Indeed, doxorubicin caused a reduction in body weight and gastrocnemius muscle weight, accompanied by an increase in hydrogen peroxide, protein oxidation, and lipid peroxidation in the gastrocnemius muscle. On the other hand, vitamin C was able to prevent the loss of skeletal muscle mass as well as the increase in markers of OS. In addition, negative correlations were found between gastrocnemius muscle mass and markers of cellular damage. In conclusion, vitamin C appears to be a protective agent against doxorubicin-induced skeletal muscle atrophy and OS. This suggests its potential application as a prophylactic measure for patients undergoing doxorubicin treatment.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"200-207"},"PeriodicalIF":1.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405757","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