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European Journal of Pharmacology

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https://www.readbyqxmd.com/read/29452086/ameliorative-effects-of-clonidine-on-ethanol-induced-kidney-injury-in-rats-potential-role-for-imidazoline-1-receptor
#1
Nesreen M I M Elkomy, Islam A A E-H Ibrahim, Shimaa M Elshazly, Hassan M El-Fayoumi
Chronic alcoholism is a risk factor for kidney injury. Clonidine is an α 2 -adrenergic receptor/imidazoline-1 receptor agonist that can reduce blood pressure and maintain renal functions. This study aims to investigate the possible ameliorative effects of clonidine on ethanol induced kidney injury and its mechanism of action. Kidney injury was induced in rats by adding ethanol to drinking water for eight weeks. Clonidine effects on kidney functions and histopathology were measured. Moreover, phentolamine (α-adrenergic receptor antagonist), efaroxan (imidazoline-1 receptor antagonist) and rilmenidine (imidazoline-1 receptor agonist) were used to clarify the role of imidazoline-1 receptor in mediating renal ameliorative effects...
February 13, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29444470/effect-of-sirolimus-on-liver-cirrhosis-and-hepatic-encephalopathy-of-common-bile-duct-ligated-rats
#2
Kuo-Cheng Wu, Hui-Chun Huang, Ting Chang, Wen-Shin Lee, Chiao-Lin Chuang, I-Fang Hsin, Shao-Jung Hsu, Fa-Yauh Lee, Ching-Chih Chang, Shou-Dong Lee
Cirrhosis is often associated with portal hypertension and portal-systemic collateral vessels formation attributed to angiogenesis, which leads to severe complications as hepatic encephalopathy. Sirolimus has anti-fibrosis and anti-angiogenesis effects, but whether it influences the severity of portal-systemic collaterals and hepatic encephalopathy is unknown. This study was thus designed to address this issue in rats with common bile duct ligation-induced liver cirrhosis. Sham-operated rats were surgical controls...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29444469/mangiferin-prevents-diabetic-nephropathy-progression-and-protects-podocyte-function-via-autophagy-in-diabetic-rat-glomeruli
#3
Xiaodan Wang, Lihui Gao, Hua Lin, Jingling Song, Jinwen Wang, Yumin Yin, Jianghu Zhao, Xiangwei Xu, Zhenkun Li, Ling Li
Diabetic nephropathy (DN) is one of the most severe microangiopathies of diabetes mellitus and is a leading cause of end stage renal disease. Numerous studies suggest that podocyte injury contributes to progressive proteinuria. Podocytes are highly specialized, terminally differentiated cells that are unable to proliferate, autophagy plays a key role in maintaining the structure and function of podocytes. Autophagy impairment is involved in the pathogenesis of podocyte loss, which leads to massive proteinuria in DN...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29444468/a-major-component-of-vitamin-e-%C3%AE-tocopherol-inhibits-the-anti-tumor-activity-of-crizotinib-against-cells-transformed-by-eml4-alk
#4
Yuki Uchihara, Takayuki Kidokoro, Kenji Tago, Tadahiko Mashino, Hiroomi Tamura, Megumi Funakoshi-Tago
Crizotinib is an inhibitor of anaplastic lymphoma kinase (ALK) and is of significant therapeutic benefit to patients with non-small cell lung cancer (NSCLC) harboring the EML4-ALK fusion gene. In the present study, we demonstrated that α-tocopherol, a major component of vitamin E, attenuated the effects of crizotinib independently of its anti-oxidant properties. α-Tocopherol significantly inhibited crizotinib-induced apoptosis in cells transformed by EML4-ALK. It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory effects of crizotinib on EML4-ALK-mediated transformation in the focus formation assay...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29438706/a-novel-role-of-the-antitumor-agent-tricyclodecan-9-yl-xanthogenate-as-an-open-channel-blocker-of-kcnq1-kcne1
#5
Meikui Wu, Makoto Takemoto, Huan Luo, Jian-Jun Xu, Mei-Hong Lu, Masaki Kameyama, Toru Takumi, Wen-Jie Song
Tricyclodecan-9-yl-xanthogenate (D609) is widely known for its antitumor and antiviral properties via the inhibition of phosphatidylcholine-specific phospholipase C and sphingomyelin synthase. Previously, we found that chronic application of D609 suppressed the K + channel, KCNQ1/KCNE1, more drastically than expected from its actions on the enzymes, suggesting a direct action of D609 on the channel. Here, we aimed to test this possibility by studying the affinity, specificity, and mechanisms of D609 on KCNQ1/KCNE1...
February 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29438705/protective-effect-of-hydroxysafflor-yellow-a-alone-or-in-combination-with-acetylglutamine-on-cerebral-ischemia-reperfusion-injury-in-rat-a-pet-study-using-18-f-fuorodeoxyglucose
#6
Ling Deng, Haitong Wan, Huifen Zhou, Li Yu, Yu He
Hydroxysafflor yellow A (HSYA) and acetylglutamine (NAG) are extensively applied in the treatment of brain injury. In this study, we investigated the neuroprotective effect and underlying mechanism of HSYA alone or together with NAG using a rat model of cerebral ischemia reperfusion injury. Male Sprague-Dawley (SD) rats (n=5) were intraperitoneally injected with 5, 10, 20mg/kg HSYA, 300mg/kg NAG and 10mg/kg HSYA+300mg/kg NAG after the onset of reperfusion and once each day for the following 7 days. After assessing the neurological deficit and infarct volume, we used18F-FDG-PET to evaluate the regional cerebral metabolic rate of glucose consumption, immunohistochemical analysis to detect the expression of GFAP, NGF, Bcl-2, Bax, caspase-3 and ICAM-1 in brain tissue at day 7 after cerebral I/R injury...
February 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29438704/nicorandil-inhibits-mechanical-allodynia-induced-by-paclitaxel-by-activating-opioidergic-and-serotonergic-mechanisms
#7
Marcela I Morais, Felipe F Rodrigues, Sarah O A M Costa, Franciele A Goulart, Fábio C Costa, Ivo S F Melo, Paulo S A Augusto, Marcela M G B Dutra, Ângelo de Fátima, Márcio M Coelho, Renes R Machado
Recently, we demonstrated that nicorandil exhibits activities in models of inflammatory and nociceptive pain. In the present study, we extended this investigation by evaluating the effects of nicorandil in models of neuropathic pain induced by paclitaxel or nerve injury in mice. Four intraperitoneal (i.p.) injections of paclitaxel (2mg/kg.day, cumulative dose 8mg/kg) or chronic constriction injury (CCI) of the sciatic nerve induced a long lasting mechanical allodynia. Per os (p.o.) administration of two doses of nicorandil (50, 100 and 150mg/kg) on the 14 th day after the first paclitaxel injection attenuated the mechanical allodynia...
February 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29438703/etizolam-attenuates-the-reduction-in-cutaneous-temperature-induced-in-mice-by-exposure-to-synthetic-predator-odor
#8
Sadaharu Miyazono, Kaede Hasegawa, Seri Miyazaki, Hikari Sakakima, Shun Konno, Saori Meguro, Hitoshi Sasajima, Tomohiro Noguchi, Kazumi Osada, Makoto Kashiwayanagi
Anxiety- and stress-related disorders can be debilitating psychiatric conditions in humans. To prevent or ameliorate these conditions, reliable animal models are needed to evaluate the effects of anxiolytic drugs. Previously, we found that a mixture of three pyrazine analogues (P-mix) that were present at high levels in wolf urine induced fear-related responses in mice, rats and deer. A change in cutaneous temperature was shown to be induced by acute stress simultaneously with changes in heart rate, arterial pressure and freezing behavior, raising the possibility that cutaneous temperature could be used as an index of stress...
February 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29438702/the-cytogenetic-effects-of-silibinin-alone-and-in-combination-with-methotrexate-in-mouse-bone-marrow
#9
Hayder Gaeed Oufi
The use of herbal drugs for disease treatment has increased worldwide. Flavonolignan silibinin, the major biologically active component of milk thistle (Silybum marianum), has various biological effects. This study is designed to evaluate the cytogenetic effects of flavonolignan silibinin in mouse bone marrow cells alone and in combination with methotrexate. In this study, the cytogenetic effects of flavonolignan silibinin were observed in mouse bone marrow cells after five days of treatment with a single intraperitoneal (IP) dose of either 50, 100 or 150mg/kg body weight of silibinin hemisuccinate (SHS), alone or in combination with a single dose of 20mg/kg methotrexate (MTX)...
February 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29438701/chronic-ethanol-consumption-increases-vascular-oxidative-stress-and-the-mortality-induced-by-sub-lethal-sepsis-potential-role-of-inos
#10
Carla S Ceron, Gabriel T do Vale, Janaina A Simplicio, Sthefany T Ricci, Bruno S De Martinis, Andressa de Freitas, Carlos R Tirapelli
We hypothesized that long-term ethanol consumption would increase the mortality and aggravate the deleterious effects of sub-lethal cecal ligation and puncture (SL-CLP) in the vasculature by inducing the expression of inducible nitric oxide (NO) synthase (iNOS). Male C57BL/6J wild-type (WT) or iNOS-deficient mice (iNOS -/- ) were treated with ethanol (20% v/v) for 12 weeks and then subjected to SL-CLP. Mice were killed 24h post-operatively or followed six days for survival. Septic ethanol-treated mice showed a higher mortality than septic WT mice...
February 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29432709/neprilysin-inhibition-and-endothelin-1-elevation-focus-on-the-kidney
#11
Lodi C W Roksnoer, Estrellita Uijl, René de Vries, Ingrid M Garrelds, A H Jan Danser
Increasing the degree of renin-angiotensin system (RAS) blockade by combining ≥2 RAS blockers marginally increases efficacy, but results in more side effects. Hence, interference with other systems is currently being investigated, like potentiation of natriuretic peptides with neprilysin inhibitors. However, the neprilysin inhibitor thiorphan was recently found to increase endothelin-1 when administered to TGR(mREN2)27 (Ren2) rats on top of RAS blockade. Here we investigated whether this effect is thiorphan-specific, by comparing the neprilysin inhibitors thiorphan and sacubitril, administered by osmotic minipumps at a low or high dose for 7 days, in Ren2 rats...
February 9, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29428472/a-novel-harmine-derivative-n-4-hydroxycarbamoyl-benzyl-1-4-methoxyphenyl-9h-pyrido-3-4-b-indole-3-carboxamide-hbc-as-histone-deacetylase-inhibitor-in-vitro-antiproliferation-apoptosis-induction-cell-cycle-arrest-and-antimetastatic-effects
#12
Jie-Fei Miao, Yan-Fu Peng, Shi Chen, Wei-Jie Gao, Qiu-Xing Yang, Peng Zhu, Jing Guo, Jinhua Tao, Lin Luo, Yanan Zhang, Yong Ling
This study aims to design and synthesize a novel harmine derivative N-(4-(hydroxycarbamoyl) benzyl)-1-(4-methoxyphenyl)-9H-pyrido [3,4-b]indole-3-carboxamide (HBC) as histone deacetylase (HDAC) inhibitor, and evaluate its antitumor activities and anti-metastasis mechanism. HBC not only exerted significant ant-proliferation activity against five human cancer cell lines, especially for HepG2 cell with an IC50 value of 2.21μM, which is nearly three-fold lower than SAHA (IC50 = 6.26µM), but also showed selective HDAC1/6 inhibitory effects in vitro...
February 8, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29428471/efficacy-of-constant-long-term-delivery-of-ym-58483-for-the-treatment-of-rheumatoid-arthritis
#13
Maya Miyoshi, Shuang Liu, Asuka Morizane, Erika Takemasa, Yashuyuki Suzuki, Takeshi Kiyoi, Kazutaka Maeyama, Masaki Mogi
The aim of this study was to investigate the efficacy and safety of YM-58483, a small molecular antagonist of Ca2+ release-activated Ca2+ (CRAC) channels, for the treatment of rheumatoid arthritis (RA), in vivo and ex vivo. YM-58483 was continuously injected subcutaneously in a collagen-induced arthritis (CIA) mouS.E.M.odel using an implanted osmotic pump. The severity of CIA was evaluated using the following parameters: body weight, hind paw volume, clinical score, histological analysis, cytokine levels, Ca2+ influx, and specific IgG production...
February 8, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29428470/dsp-6952-a-novel-5-ht4-receptor-partial-agonist-inhibits-visceral-hypersensitivity-and-ameliorates-gastrointestinal-dysfunction-in-experimental-animals
#14
Yukiko Mine, Tomohiro Itakura, Seiko Oku, Reiko Asada, Isao Shimizu
The pharmacological profile of DSP-6952, a novel 5-HT4 receptor partial agonist, was investigated to evaluate the potential use for GI disorders, and to compare its effects in some GI dysfunction models with those of clinically efficacious prokinetic agents. DSP-6952 enhanced gastric motility and caused colonic giant migrating contractions (GMCs) associated with defecation in conscious dogs, having ED50 value for inducing GMCs of 1.56mg/kg. DSP-6952 (3-10mg/kg, i.g.) significantly enhanced colonic transit rate in guinea pigs; this enhancement was antagonized by SB-207266, a selective 5-HT4 receptor antagonist...
February 8, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29428469/treatment-with-escitalopram-modulates-cardiovascular-function-in-rats
#15
Luiz Fernando Veríssimo, Vinicius Lucca Volpini, Viviane Batista Estrada, Natália Kimie Matsubara, Marcus Vinicius Gomes, Leonardo Barbosa Moraes Resstel, Fernando Morgan Aguiar Correa, Gislaine Garcia Pelosi
Considering depression is three times more common in cardiac patients compared to the normal population and selective serotonin reuptake inhibitors (SSRI) as drug of choice for treating patients with cardiovascular disease and depression, our work aims to evaluate the cardiovascular effects of treatment for 21 days with escitalopram (5 mg/kg/day, ip) in rats. The treatment caused an increase in mean arterial pressure concomitant with a decrease in heart rate. Concerning heart rate variability, there was a significant reduction in the sympathetic component and an elevation of the parasympathetic component, indicating that escitalopram caused an autonomic imbalance with parasympathetic predominance...
February 8, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29428468/the-effect-of-levetiracetam-on-rat-bone-mineral-density-bone-structure-and-biochemical-markers-of-bone-metabolism
#16
Iva Karesova, Julius Simko, Sona Fekete, Eva Zimcikova, Jana Malakova, Helena Zivna, Ladislava Pavlikova, Vladimir Palicka
Some data suggest that exposure to levetiracetam (LEV) might be associated with a risk for bone health in the model of orchidectomized rats. The aim of this study was to investigate if there is any significant risk of LEV for bone health in the model of gonadally intact animals. Wistar rats were divided into a control group and a test group, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed SLD enriched with LEV for 12 weeks. Dual energy X-ray absorptiometry was used to measure BMD of the whole body, femur and lumbar vertebrae...
February 8, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29427579/protective-effects-of-yangonin-from-an-edible-botanical-kava-against-lithocholic-acid-induced-cholestasis-and-hepatotoxicity
#17
Yulong Kong, Xiaoguang Gao, Changyuan Wang, Chenqing Ning, Kexin Liu, Zhihao Liu, Huijun Sun, Xiaodong Ma, Pengyuan Sun, Qiang Meng
Accumulation of toxic bile acids in liver could cause cholestasis and liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of yangonin, a product isolated from an edible botanical Kava against lithocholic acid (LCA)-induced cholestasis, and further to elucidate the involvement of farnesoid X receptor (FXR) in the anticholestatic effect using in vivo and in vitro experiments. The cholestatic liver injury model was established by intraperitoneal injections of LCA in C57BL/6 mice...
February 7, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29409911/inhibition-of-gingipains-prevents-porphyromonas-gingivalis-induced-preterm-birth-and-fetal-death-in-pregnant-mice
#18
Ryosuke Takii, Tomoko Kadowaki, Takayuki Tsukuba, Kenji Yamamoto
Accumulating epidemiological evidence indicates that infection with Porphyromonas gingivalis which is a major periodontal pathogen, causes preterm birth and low birth weight. However, virulence factors of P. gingivalis responsible for preterm birth/low birth weight remain to be elucidated. In this study, using P. gingivalis-infected pregnant mice as an in vivo model, we investigated whether gingipains-cysteine proteinases produced by P. gingivalis-affect preterm birth and low birth weight. We found that intravenous infection of pregnant mice with P...
February 6, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29409910/sp600125-blocks-the-proteolysis-of-cytoskeletal-proteins-in-apoptosis-induced-by-gas-signaling-molecule-no-via-decreasing-the-activation-of-caspase-3-in-rabbit-chondrocytes
#19
Xi-Bin Kao, Qun Chen, Yan Gao, Pin Fan, Jing-Hong Chen, Zhi-Lun Wang, Yan-Qi Wang, Ya-Ni Chen, Yong-Ping Yan
NO plays a key role in the pathological mechanisms of articular diseases. As cytoskeletal proteins are responsible for the polymerization, stabilization, and dynamics of the cytoskeleton network, we investigated whether cytoskeletal proteins are the intracellular pathological targets of NO. We aimed at clarifying whether the cytoskeleton perturbations involved in apoptosis are induced in rabbit articular chondrocytes by NO, which can be liberated by sodium nitroprusside (SNP) treatment. The first passage rabbit articular chondrocytes were cultured as monolayer for the experiments, and the effects of NO were tested in the presence of JNK-specific inhibitor, SP600125...
February 6, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29408089/anti-allodynic-effects-of-n-demethylsinomenine-an-active-metabolite-of-sinomenine-in-a-mouse-model-of-postoperative-pain
#20
Yuntao Ou, Man Su, Yong Ling, Qianqian Wei, Fei Pan, Jiejia Li, Jun-Xu Li, Qing Zhu
Sinomenine, a major bioactive ingredient isolated from traditional Chinese medicine Sinomenium acutum, has been reported to have analgesic effects in various pain animal models. N-demethylsinomenine, the N-demethylated product of sinomenine, has been identified to be the major metabolite of sinomenine and is also a natural component extracted from Sinomenium acutum. This study examined the anti-allodynic effects of N-demethylsinomenine in a mouse model of postoperative pain. A significant and sustained mechanical allodynia that lasted for 4 days was induced by making a surgical incision on the right hind paw in mice...
February 3, 2018: European Journal of Pharmacology
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