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Canadian Journal of Physiology and Pharmacology

Modinat Adebukola Adefisayo, Wale Johnson Adeyemi, Quadri Kunle Alabi
Although cisplatin is a potent anticancer drug, it instigates oxidative and pro-inflammatory reactions which poses significant and distressing clinical symptoms in patients including nausea and vomiting which is related to damage of the gastric mucosa. This study investigated the effects of vitamin C and/or L-carnitine on cisplatin-induced gastric mucosa damage in rat. The rats were allocated into groups (n=5): a control group received distilled water and treatment groups received cisplatin (CIP) alone, cisplatin followed by vitamin C, L-carnitine or their combination...
April 20, 2018: Canadian Journal of Physiology and Pharmacology
Natalia Kurhaluk, Bianka Bojková, Pawel J Winklewski
Oxidative stress is involved in the development of various cancers. In the present study the effect of long-term administration of peroral antidiabetic metformin and pineal hormone melatonin on liver antioxidant and aerobic status in female Sprague-Dawley rats carrying mammary tumors induced by N-methyl-N-nitrosourea was evaluated. Both substances were administered in a preventive/curative manner (12 days before and 16 weeks after the carcinogen application). Carcinogen administration induced oxidative stress: the level of thiobarbituric acid reactive products (TBARS) as a marker of reactive oxygen species (ROS) generation in liver increased as well as the level of oxidatively modified protein content (OMP, aldehyde and ketone derivates)...
April 15, 2018: Canadian Journal of Physiology and Pharmacology
Yuanfa Yao, Xuqin Zhao, Jinxia Xin, Yingqi Wu, Hanbing Li
Coumarins extensively exist in plants and are utilized against diabetes in some folk medicines. Recent studies have demonstrated that oxidative stress plays a crucial role in the etiology and pathogenesis of diabetes mellitus. We investigated the antioxidant ability of three coumarins (osthole, esculin and fraxetin) in type 2 diabetes. After high-fat diet fed, ICR mice were exposed to low doses of streptozotocin and then treated with experimental coumarins for five weeks. We found osthole, esculin and metformin significantly lowered FBG, HOMA-IR and three blood lipids (T-CHO, TG, NEFA), and increased insulin levels, while fraxetin only enhanced insulin levels and lessened NEFA...
April 11, 2018: Canadian Journal of Physiology and Pharmacology
Amna Naser, Ahmad Qasem, Saleh A Naser
Patients with Crohn's disease have higher risk for osteoporosis following decreased level of osteocalcin. We hypothesize that active inflammation following Mycobacterium avium subspecies paratuberculosis (MAP) infection results in elevation of undercarboxylated Osteocalcin (ucOC) and downregulation of active Osteocalcin in CD patients and cow disease-model (Johne's disease). In this study, we measured ucOC, active osteocalcin and calcium levels in sera from 42 cattle (21 infected with MAP and 21 healthy cattle), 18 CD patients and 20 controls...
April 11, 2018: Canadian Journal of Physiology and Pharmacology
Tomas Baka, Július Hodosy, Kristina Krajcirovicova, Kristina Repova, Silvia Aziriova, Emese Domonkos, Veronika Borbelyova, Peter Slavkovsky, Stefan Zorad, Peter Celec, Ludovit Paulis, Fedor Simko
No data are available on heart function in chronic testosterone deficiency and on the effect of estrogen treatment. Eighteen 4-week-old male Lewis rats were randomly divided into three groups (n = 6): one group of sham-operated rats and two groups of castrated rats. 66 weeks after surgery, one castrated group received a dose of 17β-estradiol (10 μg/kg/day) and the remaining two groups received a placebo subcutaneously for 14 days. Left ventricular (LV) systolic and diastolic functions were measured by transthoracic echocardiography...
April 10, 2018: Canadian Journal of Physiology and Pharmacology
Bohuslav Ostadal, Antonin Parizek, Ivana Ostadalova, Frantisek Kolar
Catecholamines are involved in the regulation of a wide variety of vital functions. The β-adrenergic receptor (β-AR) - adenylyl cyclase (AC) system has been identified early in embryogenesis before the heart has received adrenergic innervation. The structure of β-receptors in the immature myocardium is similar to that in adults; there are, however, significant quantitative developmental changes in the inotropic and chronotropic responsiveness. Information on the toxic effect of the β-AR agonists in the immature heart is surprisingly scarce, even though these agents are used in clinical practice both during pregnancy and in early postnatal development...
April 10, 2018: Canadian Journal of Physiology and Pharmacology
Yi Zhao, Sergio Fabris, David A MacLean
The purpose of the present study was to utilize the microdialysis technique in rat skeletal muscle to perfuse varying concentrations of AMP, ADP and ATP into the interstitium to examine the effects that these adenine nucleotides have on the production of adenosine in the interstitial space. The interstitial adenosine production appears to be directly related to the concentrations of its substrates ATP, ADP, and AMP. Interstitial adenosine levels increased (P<0.05) from baseline (0.18±0.02 μM) to 0.23±0...
April 10, 2018: Canadian Journal of Physiology and Pharmacology
Shiori Nakagawa, Takayuki Ueno, Takayuki Manabe, Kiyoshi Kawasaki
This study evaluated whether imidazolines can induce autophagy in the murine macrophage-like cell line RAW264.7. Idazoxan increased the content of LC3-II, an autophagosomal marker, in RAW264.7 cells. To determine whether this effect was due to the induction of its synthesis or inhibition of its degradation, idazoxan-treatment was performed in the presence of bafilomycin A<sub>1</sub>, which blocks autophagosome-lysosome fusion, as well as Pepstatin A and E-64d, both of which block protein degradation in autolysosomes...
April 10, 2018: Canadian Journal of Physiology and Pharmacology
Hanming Wang, Wan-Zhu Liu, Futian Tang, Hai-Juan Sui, Xing-Jie Zhan, Hongxin Wang
Tissue transglutaminase (TG2) plays an important role in pulmonary arterial hypertension (PAH). Previous researches indicate that TG2 and protein serotonylation catalyzed by TG2 are upregulated in PAH. Serotonin transporter inhibitor fluoxetine ameliorates PAH via inhibition of protein serotonylation. It is still unknown whether PAH is inhibited through direct inhibition of TG2. Therefore, the present study aimed to investigate the effects of TG2 inhibitor cystamine on monocrotaline-induced PAH in rats. Rats were treated with monocrotaline (60 mg•kg-1, i...
April 10, 2018: Canadian Journal of Physiology and Pharmacology
Burak DiK, Emre Bahcivan, Hatice Eser Faki, Kamil Uney
In the present study, combined treatment with etanercept and anakinra were tested in the streptozotocin-induced diabetic rats. Forty male Wistar albino rats were divided into 5 groups; healthy control (HC), diabetic control (DC), diabetic+anakinra (DAT), diabetic+etanercept (DET), and diabetic+etanercept+anakinra (DEAT). HC and DC groups received subcutaneous (sc.) injection with a saline solution, while DAT and DET groups received anakinra (10 mg/kg/day, sc.) or etanercept (10 mg/kg, twice a week, sc.), and DEAT rats received both anakinra and etanercept treatments for 21 days after diabetes has developed...
March 20, 2018: Canadian Journal of Physiology and Pharmacology
Hossein Amini-Khoei, Nastaran Kordjazy, Arya Haj-Mirzaian, Shayan Amiri, Arvin Haj-Mirzaian, Armin Shirzadian, Amin Hasanvand, Shima Balali-Dehkordi, Mahsa Hassanipoor, Ahmad Reza Dehpour
Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole (PTZ)-induced seizures in mouse considering the possible role of nitric oxide (NO)/NMDA pathway. We induced seizure using intravenous administration of PTZ. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of sub-effective doses of the non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (10 mg/kg) and the neuronal NOS inhibitor, 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of sub-effective dose of minocycline (40 mg/kg)...
March 20, 2018: Canadian Journal of Physiology and Pharmacology
Makoto Ando, Takayuki Matsumoto, Shota Kobayashi, Maika Iguchi, Kumiko Taguchi, Tsuneo Kobayashi
The purpose of this study was to determine the relationship of KCa channels to endothelium-dependent hyperpolarizing factor (EDHF)-mediated relaxation induced by acetylcholine (ACh) in the superior mesenteric arteries of 7-month-old spontaneously hypertensive rats (SHR). Upon inhibition of nitric oxide synthase and cyclooxygenase, ACh-induced EDHF-mediated relaxation was found to be weaker in SHR than in age-matched Wistar Kyoto rats (WKY). These relaxations in both group were attenuated by combined treatment with small-conductance and intermediate-conductance Ca2+-activated K+ channels (SKCa and IKCa) inhibitors, with the exception of relaxation resistant to inhibition of these channels in SHR (vs...
March 20, 2018: Canadian Journal of Physiology and Pharmacology
Sowmya Mekala, Subbarao V Tullimilli, Ramasatyaveni Geesala, Kanakaraju Manupati, Neha R Dhoke, Amitava Das
Apoptotic hepatocytes release factors that activate Hepatic Stellate Cells (HSCs) thereby inducing hepatic fibrosis. In the present study, in vivo and in vitro injury models were established using acetaminophen, ethanol, carbon tetrachloride or thioacetamide. Hepatotoxicant-induced diseased hepatic tissue histology correlated with a differential expression of fibrosis-related genes. Marked increase in co-staining of TGFRIIβ-Desmin or α-SMA-PDGFRβ, markers of activated HSCs, in liver sections of these hepatotoxicant-treated mice also depicted an increase in Annexin V-Cytokeratin expressing hepatocytes...
March 20, 2018: Canadian Journal of Physiology and Pharmacology
Jonathan James Weldrick, Mohammad Abdul-Ghani, Lynn A Megeney, Patrick G Burgon
The capacity to isolate and study single cardiomyocytes has dramatically enhanced our understanding of the fundamental mechanisms of the heart. Currently, two primary methods for the isolation of cardiomyocytes are employed; i) The neonatal isolation protocol and, ii) the Langendorff isolation method. A major limiting feature of both procedures is the inability to isolate cardiomyocytes between 3 days and 3 weeks post-birth. Herein we report the establishment and validation of a new method for the rapid and efficient isolation of mouse cardiomyocytes, regardless of age...
March 13, 2018: Canadian Journal of Physiology and Pharmacology
Min Jiang, Qiang Lyu, Yun-Gang Bai, Huan Liu, Jing Yang, Jiu-Hua Cheng, Ming Zheng, Jin Ma
Recent studies have suggested that microgravity-induced arterial remodelling contributes to post-flight orthostatic intolerance and that multiple mechanisms are involved in arterial remodelling. However, the initial mechanism by which haemodynamic changes induce arterial remodelling is unknown. Focal adhesions (FAs) are dynamic protein complexes that have mechanotransduction properties. This study aimed to investigate the role of FAs in simulated microgravity-induced basilar and femoral arterial remodelling...
March 11, 2018: Canadian Journal of Physiology and Pharmacology
M Bilgehan Pektas, Ozge Turan, Gozde Ozturk Bingol, Esra Sumlu, Gökhan Sadi, Fatma Akar
Transient elevations in blood glucose level may lead to changes in vascular function. Herein, we investigated the effects of high-glucose or high-fructose challenge as well as potential influence of juglone or resveratrol on vascular reactivity, Akt/eNOS and insulin signaling effectors in rat aorta. Aortic segments of rats were incubated with high-glucose (30 mM) or high-fructose (2 mM) in the absence and presence of juglone (5 μM) or resveratrol (10 μM). Acute high-glucose incubation markedly decreased acetylcholine-induced relaxation, which is further inhibited by juglone, but ameliorated by resveratrol...
March 10, 2018: Canadian Journal of Physiology and Pharmacology
Houda Bouhajja, Rania Abdelhedi, Ali Amouri, Faten Hadj Kacem, Rim Marrakchi, Wajdi Safi, Houcem Mrabet, Lassaad Chtourou, Nadia Charfi, Mouna Fourati, Salwa Bensassi, Kamel Jamoussi, Mohamed Abid, Hammadi Ayadi, Mouna Mnif Feki, Noura Bougacha Elleuch
BACKGROUND: The relationship between liver enzymes and type 2 diabetes (T2D) risk is inconclusive. We aimed to evaluate the association between liver markers and risk of carbohydrate metabolism disorders and their discriminatory power for T2D prediction. METHODS: This cross-sectional study enrolled 216 participants classified as normoglycemic, prediabetes, newly-diagnosed diabetes and diagnosed diabetes. All participants underwent anthropometric and biochemical measurements...
March 10, 2018: Canadian Journal of Physiology and Pharmacology
Amir M Abdelhamid, Rania Ramadan Abdelaziz, Hatem A Salem
Type I diabetes (TID) is generally assumed to be caused by an immune associated, if not directly immune-mediated, destruction of pancreatic β-cells. In patients with long-term diabetes, the pancreas lacks insulin-producing cells and the residual β-cells are unable to regenerate. Patients with TID are subjected to a lifelong insulin therapy which shows risks of hypoglycemia, suboptimal control and ketosis. In this study, we investigated the potential role of Vildagliptin (Vilda) alone or in combination with Pioglitazone (Pio), as treatment regimens for TID using Streptozotocin (STZ) induced TID model in rats...
March 6, 2018: Canadian Journal of Physiology and Pharmacology
Jing Gao, Yuhong Li, Tongmei Wang, Zhuo Shi, Yiqi Zhang, Shuang Liu, Pushuai Wen, Chunyan Ma
The aim of this study was to identify the key genes involved in the cardiac hypertrophy (CH) induced by pressure overload. mRNA microarray dataset GSE5500 and GSE18801 were downloaded from GEO database, and differentially expressed genes (DEGs) were screened using Limma package; then, functional and pathway enrichment analysis were performed for common DEGs using DAVID database. Furthermore, the top DEGs were further validated using qPCR in the hypertrophic heart tissue induced by Isoprenaline (ISO). A total of 113 common DEGs with absolute fold change >0...
March 6, 2018: Canadian Journal of Physiology and Pharmacology
Bo Chu, Yadong Zhou, Heng Zhai, Lei Li, Li Sun, Yun Li
MicroRNA-146a (miR-146a) is reportedly implicated in the pathogenesis of ischemia/reperfusion (I/R) injury. Its role in the cerebral I/R injury is however unclear and requires further investigation. In this study, cerebral I/R injury was established in mice via middle cerebral artery occlusion (MCAO), and the expression of miR-146a was detected in the brain tissue via quantitative real-time PCR. We found that the expression of miR-146a was up-regulated. Furthermore, the endogenous miR-146a was antagonized by its specific inhibitor...
March 5, 2018: Canadian Journal of Physiology and Pharmacology
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