Canadian journal of physiology and pharmacology最新文献

Effects of acute aerobic exercise on skeletal muscle and liver glucose metabolism in male rodents with type 1 diabetes. 急性有氧运动对1型糖尿病雄性啮齿动物骨骼肌和肝脏葡萄糖代谢的影响

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-04-01 Epub Date: 2025-01-15 DOI: 10.1139/cjpp-2024-0226

Justin A Camenzuli, Mitchell J Sammut, Theres Tijo, C W James Melling

{"title":"Effects of acute aerobic exercise on skeletal muscle and liver glucose metabolism in male rodents with type 1 diabetes.","authors":"Justin A Camenzuli, Mitchell J Sammut, Theres Tijo, C W James Melling","doi":"10.1139/cjpp-2024-0226","DOIUrl":"10.1139/cjpp-2024-0226","url":null,"abstract":"Aerobic exercise (AE) is associated with a significant hypoglycemia risk in individuals with type 1 diabetes mellitus (T1DM). However, the mechanisms in the liver and skeletal muscle governing exercise-induced hypoglycemia in T1DM are poorly understood. This study examined the effects of a 60-min bout of AE on hepatic and muscle glucose metabolism in T1DM rats. Nineteen male Sprague-Dawley rats were divided into sedentary (SC; n = 5) and T1DM (DSC; n = 14) groups. T1DM rats were subcategorized into pre-exercise (DPRE; n = 6) and post-exercise (DPOST; n = 8). DPOST were sacrificed immediately after 60 min of AE. Results demonstrate that DPOST animals experienced reductions in BG following 30 and 60 min of AE compared to pre-exercise. Both DPRE and DPOST animals exhibited lower hepatic glycogen content, while muscle glycogen did not differ, suggesting impaired glycogenolysis in T1DM. Hepatic glucose-6-phosphatase content, and muscle and hepatic protein kinase B phosphorylation were significantly greater in DPOST animals, suggesting elevated gluconeogenesis and insulin stimulation during exercise. Glycogen phosphorylase activity did not differ between groups. These data suggest that drops in BG during AE in T1DM were due to lower glycogen levels in the liver and muscle and a lack of muscle glycogen utilization; leading to a reliance on gluconeogenesis and BG.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"123-133"},"PeriodicalIF":1.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000754","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

Histamine H₃ receptor activation increases the firing of striatal medium spiny neurons in slices from infantile rats.

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-04-01 Epub Date: 2025-02-13 DOI: 10.1139/cjpp-2024-0240

Carolina González-Sandoval, Isabel Godínez-Ramos, José-Antonio Arias-Montaño, Jaime Barral

{"title":"Histamine H3 receptor activation increases the firing of striatal medium spiny neurons in slices from infantile rats.","authors":"Carolina González-Sandoval, Isabel Godínez-Ramos, José-Antonio Arias-Montaño, Jaime Barral","doi":"10.1139/cjpp-2024-0240","DOIUrl":"10.1139/cjpp-2024-0240","url":null,"abstract":"Striatal medium spiny neurons (MSN) form two subpopulations (MSN-D1 and MSN-D2) according to the expression of dopamine D1 or D2 receptors and their target regions. The activation of postsynaptic histamine H1 and H2 receptors increases MSN-D1 and MSN-D2 excitability. Since MSN also express H3 receptors (H3Rs), in this work we explored the effect of their activation on MSN firing. Electrophysiological recordings (whole-cell patch-clamp, current-clamp mode) were conducted on forebrain slices from infantile rats (12-16 postnatal days). In both MSN-D1 and MSN-D2 perfusion with the H3R agonist immepip (1 µmol/L) increased neuronal firing evoked by current injection, an effect reproduced by R-α-methylhistamine (1 µmol/L) and prevented by the antagonist clobenpropit (10 µmol/L). Blockade of N- or P/Q-type voltage-activated calcium channels by ω-conotoxin-GVIA (1 µmol/L) or ω-agatoxin-TK (400 nmol/L) increased MSN firing but did not preclude the immepip effect. The potassium channel blockers 4-aminopyridine (1 mmol/L) and tetraethylammonium (300 µmol/L) increased neuronal firing and prevented the immepip action. Likewise, the KV7 channel blocker XE-991 (10 µmol/L) and the muscarinic receptor agonist carbachol (10 µmol/L) increased MSN firing frequency and occluded the immepip effect. These data indicate that the activation of postsynaptic H3Rs facilitates MSN-D1 and MSN-D2 firing by inhibiting KV7 potassium channels.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"134-145"},"PeriodicalIF":1.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413499","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 addictive process of opioids: current and novel interventions in opioid use disorder.

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-04-01 Epub Date: 2025-02-11 DOI: 10.1139/cjpp-2024-0281

James M Duerksen, Matthew Ramjiawan, Julia Witt, Shirley Fitzpatrick-Wong, Paramjit S Tappia, Bram Ramjiawan, Behzad Mansouri, Jitender Sareen, Erin Knight

{"title":"The addictive process of opioids: current and novel interventions in opioid use disorder.","authors":"James M Duerksen, Matthew Ramjiawan, Julia Witt, Shirley Fitzpatrick-Wong, Paramjit S Tappia, Bram Ramjiawan, Behzad Mansouri, Jitender Sareen, Erin Knight","doi":"10.1139/cjpp-2024-0281","DOIUrl":"10.1139/cjpp-2024-0281","url":null,"abstract":"The growing epidemic of opioid misuse presents numerous challenges for healthcare practitioners and patients alike as friction exists between ease of use and efficacy, and potential for overuse and addiction. With over 82 000 deaths related to opioid overdose in North America in 2020, it is imperative to gain a better understanding of the underlying mechanisms behind the addiction process, as well as the current methods being used in the arsenal against this disease. The current best pharmacological approaches for mediating opioid use disorder are methadone, buprenorphine, naltrexone, and naloxone, which act on opioid receptors to produce diverse effects based upon the patients' needs. The variety of effects that these drugs produce, which include removing opioid withdrawal, reversing overdose effects, and blocking opioid properties, makes this arsenal of therapeutics a global necessity in addressing the opioid use epidemic. Accordingly, this narrative review provides a summary of the available data regarding the physiological processes by which opioid addiction takes place and discusses the current and future potential of interventional methods used to mitigate opioid use disorder. The mechanisms of action and subsequent functional outcomes must be understood to reduce the number of opioid-related deaths worldwide.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"111-122"},"PeriodicalIF":1.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398201","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 vs. children.

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub 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 vs. 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":"https://doi.org/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 to 13. Adult- and child-based PGS 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 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 PGS 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":""},"PeriodicalIF":1.7,"publicationDate":"2025-03-25","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

Systematic Review of Health Canada Authorized Clinical Therapeutic Trials for the Treatment or Prevention of Coronavirus Disease 2019 (COVID-19).

IF 1.7 4区医学

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

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

引用次数: 0

Epicardial Adipose Tissue As Target of the Incretin-Based Therapies in Cardio-Metabolic Pathologies: A Narrative Review.

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-03-06 DOI: 10.1139/cjpp-2024-0384

Andrea Sk Pop, Maria D Danila, Silvia Giuchici, Darius G Buriman, Bogdan M Lolescu, Adrian Sturza, Danina M Muntean, Ana Lascu

{"title":"Epicardial Adipose Tissue As Target of the Incretin-Based Therapies in Cardio-Metabolic Pathologies: A Narrative Review.","authors":"Andrea Sk Pop, Maria D Danila, Silvia Giuchici, Darius G Buriman, Bogdan M Lolescu, Adrian Sturza, Danina M Muntean, Ana Lascu","doi":"10.1139/cjpp-2024-0384","DOIUrl":"https://doi.org/10.1139/cjpp-2024-0384","url":null,"abstract":"The epicardial adipose tissue (EAT) serves in physiological conditions as a mechanical and thermal myocardial protective layer, as well as a readily available lipid-storage unit. In pathological conditions, EAT expansion becomes deleterious and is currently recognized as an independent risk factor for the progression of cardiovascular diseases. The EAT phenotypic shift from protective to pro-inflammatory/pro-oxidant is facilitated by the presence of metabolic diseases (obesity, metabolic syndrome, and diabetes), which further increase its expansion and dysregulation, favor the occurrence of complications (mainly atrial fibrillation), and promote progression towards heart failure. Glucagon-like peptide-1 (GLP-1) receptor agonists are novel antidiabetic medications belonging to the incretin class that have demonstrated efficacy beyond glycemic control, in terms of weight reduction and cardio-renal protection in patients with type 2 diabetes mellitus. The GLP-1 receptors and glucose-dependent insulinotropic polypeptide (GIP) receptors are expressed in the human EAT and are targeted by an increasing number of pharmacological agonists, with pleiotropic protective effects on EAT structure and function. Herein we review the literature characterizing the benefits of GLP-1 and GIP receptors activation by single and dual agonists with particular emphasis on their effects on EAT and highlight the role of incretin-based therapy for the management of cardio-metabolic pathologies.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572263","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

Right ventricular dysfunction in preclinical models of type I and type II diabetes. 1型和2型糖尿病临床前模型右心室功能障碍

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-03-01 Epub Date: 2024-12-18 DOI: 10.1139/cjpp-2024-0195

Sydney M Polson, Joshua P Thornburg, Benjamin D McNair, Christian Z Cook, Elizabeth A Straight, Kevin C Fontana, Caleb R Hoopes, Sreejayan Nair, Danielle R Bruns

{"title":"Right ventricular dysfunction in preclinical models of type I and type II diabetes.","authors":"Sydney M Polson, Joshua P Thornburg, Benjamin D McNair, Christian Z Cook, Elizabeth A Straight, Kevin C Fontana, Caleb R Hoopes, Sreejayan Nair, Danielle R Bruns","doi":"10.1139/cjpp-2024-0195","DOIUrl":"10.1139/cjpp-2024-0195","url":null,"abstract":"Diabetic cardiomyopathy (DCM) is a growing clinical entity and major health burden characterized by comorbid diabetes mellitus and heart failure. DCM has been commonly associated with impaired function of the left ventricle (LV); however, DCM likely also occurs in the right ventricle (RV) which has distinct physiology and pathophysiology from the LV. RV dysfunction is the strongest determinant of mortality in several clinical contexts yet remains poorly studied in diabetes. We investigated RV-specific pathophysiology using two models of diabetes-a well-characterized type 2 diabetes (T2DM) model of high-fat diet and low-dose streptozotocin (STZ) in the mouse and a large animal model of type I diabetes in domestic pigs rendered diabetic with STZ. RV global and systolic function deteriorated with diabetes, alongside hypertrophic and fibrotic remodeling. We report evidence of impaired RV insulin sensitivity, dysregulated RV metabolic gene expression, and impaired mitochondrial dynamics. Importantly, while some of these outcomes were similar to those widely reported in the LV, others were not, such as unchanged antioxidant gene expression and regulators of fatty acid uptake. Importantly, these RV-specific changes occurred in both male and female T2DM mice, together emphasizing the importance of distinguishing the RV from the LV when studying DCM and begging the consideration of RV-specific therapies.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"86-97"},"PeriodicalIF":1.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853137","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

Endothelial characteristics of cardiac stem cell antigen-1 expressing cells and their relevance to right ventricular adaptation.

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-03-01 Epub Date: 2025-01-22 DOI: 10.1139/cjpp-2024-0244

Kirishani Kesavan, Sheethal Panchakshari, Haya Abdelwahab, Elena Stephanie Gomez Rabelo, Ketul R Chaudhary

{"title":"Endothelial characteristics of cardiac stem cell antigen-1 expressing cells and their relevance to right ventricular adaptation.","authors":"Kirishani Kesavan, Sheethal Panchakshari, Haya Abdelwahab, Elena Stephanie Gomez Rabelo, Ketul R Chaudhary","doi":"10.1139/cjpp-2024-0244","DOIUrl":"10.1139/cjpp-2024-0244","url":null,"abstract":"A growing body of evidence suggest that the stem cell antigen-1 expressing (Sca-1+) cells in the heart may be the cardiac endothelial stem/progenitor cells. Their endothelial cell (EC) functions, and their role in right ventricle (RV) physiology and pathophysiology of right heart failure (RHF) remains poorly defined. This study investigated EC characteristics of rat cardiac Sca-1+ cells, assessed spatial distribution and studied changes in Sca-1+ cells during RV remodelling in monocrotaline (MCT) model of pulmonary hypertension and RV remodeling. First, flow-cytometry analysis of adult male and female Sprague Dawley (SD) and Fischer CDF rat heart cells was performed, and we observed that the majority of Sca-1+ cells also expressed CD31, an EC marker. Furthermore, Sca-1+ cells showed acetylated low-density lipoprotein (ac-LDL) uptake and lectin binding similar to CD31+ cells from the same heart. The Sca-1+ cells also demonstrated network formation when plated on Matrigel. In the MCT treated rats, we observed increase in RV hypertrophy that correlated with the reduction in the abundance of Sca-1+CD31+ cells in the RV. Together, the cardiac Sca-1+ cells in the heart are endothelial stem/progenitor-like cells. These cells have higher abundance in the RV and may play a role in RV adaptation.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"98-110"},"PeriodicalIF":1.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022057","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

Chemical synthesis, in vitro testing, and in silico Nampt-based molecular docking of novel aniline aromatic ring-substituted 2-aminothiazole analogs. 新型苯胺芳环取代 2-氨基噻唑类似物的化学合成、体外测试和基于 Nampt 的硅学分子对接。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-03-01 Epub Date: 2024-10-07 DOI: 10.1139/cjpp-2024-0211

Ali A Husain, Ravikumar Manickam, Jonah Gordon, Sandhya Santhana, Katarzyna Mizgalska, Wayne C Guida, Srinivas M Tipparaju, Kirpal S Bisht

{"title":"Chemical synthesis, in vitro testing, and in silico Nampt-based molecular docking of novel aniline aromatic ring-substituted 2-aminothiazole analogs.","authors":"Ali A Husain, Ravikumar Manickam, Jonah Gordon, Sandhya Santhana, Katarzyna Mizgalska, Wayne C Guida, Srinivas M Tipparaju, Kirpal S Bisht","doi":"10.1139/cjpp-2024-0211","DOIUrl":"10.1139/cjpp-2024-0211","url":null,"abstract":"The heterocyclic 2-aminothiazoles scaffolds are used in a wide range of therapeutic applications against various diseases for its antioxidant, anti-inflammatory, antimicrobial and anticancer actions. In this study, we synthesized novel aniline aromatic ring-substituted 2-aminothiazole derivatives. Molecular docking was performed using Glide module of the Schrödinger Suite to fit compounds JG-49, JG-62, and KBA-18 against the Nicotinamide phosphoribosyl transferase (Nampt) enzyme, an intracellular regulator of nicotinamide adenine dinucleotide (NAD) redox cofactor involved in energy metabolism and epigenetics and are implicated in aging and metabolic diseases. The three compounds viz. JG-49, JG-62, and KBA-18 showed an increase in Nampt enzymatic activity in vitro. All three substituted derivatives of 2-aminothiazole showed no cytotoxicity with the mouse C2C12 myoblasts cultures assessed with the MTT cell viability assay. Moreover, the wound closure of the mouse C2C12 myoblasts in vitro displayed no significant difference between the treatment groups of the 2-aminothiazole derivatives compared with the control naïve and DMSO treated myoblasts cultures, except for the 2-aminothiazole substituted derivatives JG-62 and KBA-18, which showed a significant increase in the wound closure compared with the control cells at different concentrations. Taken together, we demonstrated that 2-aminothiazole substituted derivatives provide enhanced Nampt activity, wound closure, and no cytotoxic effects in vitro. Further studies will allow to improve the substitution of 2-aminothiazole derivatives and test their potential therapeutic applications.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"75-85"},"PeriodicalIF":1.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388324","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

Examining tissue-level changes in doxorubicin accumulation and nitric oxide formation in skeletal muscle and tumours in a mouse model of breast cancer.

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub 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":""},"PeriodicalIF":1.7,"publicationDate":"2025-02-25","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