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Journal of Pharmacological Sciences

Shota Yamamoto, Nobuaki Egashira, Makoto Tsuda, Satohiro Masuda
Oxaliplatin causes acute cold hypersensitivity in most patients. We previously reported oxalate derived from oxaliplatin induced cold allodynia via overexpression of transient receptor potential melastatin 8 (TRPM8) in the dorsal root ganglion (DRG) in rats. In this study, we examined the effect of riluzole on oxaliplatin-induced cold allodynia. In cultured DRG neurons, riluzole suppressed oxalate-induced increase of the number of menthol (TRPM8 agonist)-sensitive cells. Moreover, riluzole prevented cold allodynia and increase in levels of TRPM8 mRNA in oxaliplatin-treated rats...
October 26, 2018: Journal of Pharmacological Sciences
Ho-Sung Lee, Ho Jung Shin, Munju Cho, Seung Hoon Lee, Dal-Seok Oh
The aim of this study was to assess the effects of Keishibukuryogan (K-06) and Shakuyakukanzoto (TJ-68), commercial herbal medicines, on the substrate uptake activities of renal organic anion transporters. We performed transporter uptake and cell viability assays in Xenopus oocytes and HEK293 human kidney embryonic cells treated with K-06 or TJ-68. K-06 and TJ-68 markedly inhibited the substrate uptake activities of URAT1, OAT1, and OAT3, while they did not exhibit non-cytotoxic effects. Our findings demonstrated that K-06 and TJ-68 inhibited the substrate uptake activities of renal transporters, suggesting their mechanism of action as nephroprotective agents...
October 24, 2018: Journal of Pharmacological Sciences
Wei Chen, Xuelong Qian, Yue Hu, Wei Jin, Yunlong Shan, Xianying Fang, Yang Sun, Biao Yu, Qiong Luo, Qiang Xu
Frequent local recurrence and metastasis are generally involved in human liposarcoma, but the management is a challenge. There is an urgent need for improved effective therapy. In the present study, we reported that SBF-1, a steroidal glycoside, inhibited the growth of cultured highly malignant human liposarcoma SW872-S cells in vitro and in vivo. SBF-1 down-regulated the phosphorylation of protein kinase B (AKT) and thus reduced cell adhesion to fibronectin and laminin. Then we found that SBF-1 inhibited the expression of oxysterol binding protein (OSBP) in SW872-S cells, indicating that OSBP may be involved in malignant liposarcoma cell survival...
October 24, 2018: Journal of Pharmacological Sciences
Yasunari Kanda, Daiju Yamazaki, Tomoharu Osada, Takashi Yoshinaga, Kohei Sawada
Cardiac safety assessment is challenging because a better understanding of torsadogenic mechanisms beyond hERG blockade and QT interval prolongation is necessary for patient safety. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide a new human cell-based platform to assess cardiac safety in non-clinical testing during drug development. The multi-electrode array (MEA) platform is a promising electrophysiological technology to assess QT interval prolongation and proarrhythmic potential of drug candidates using hiPSC-CMs...
October 24, 2018: Journal of Pharmacological Sciences
Eun-Ji Lee, Tae-Wook Chung, Jung-Hee Lee, Bo-Sung Kim, Eun-Yeong Kim, Syng-Ook Lee, Ki-Tae Ha
Cinnamomum cassia Blume has been widely reported as the anti-tumor agent. However, the precise mechanism underlying its pro-apoptotic action is still not clear. Restraining aerobic glycolysis through suppression of pyruvate dehydrogenase kinase (PDHK) is a promising strategy for cancer inhibition. In this study, we performed to investigate the anti-tumor action of C. cassia is mediated by PDHK inhibition. The inhibition of water-extracted branch of C. cassia (WBCC) on the activity of PDHK using both in vitro and cell-based kinase assay were examined in several lung cancer cells...
October 18, 2018: Journal of Pharmacological Sciences
Ai Goto, Mihoko Hagiwara-Nagasawa, Hiroko Izumi-Nakaseko, Kumiko Kitta, Kiyotaka Hoshiai, Koki Chiba, Kentaro Ando, Yasuki Akie, Atsuhiko T Naito, Atsushi Sugiyama
Although azithromycin can suppress cardiac INa , IKr , IKs , ICa,L and IK1 , its onset mechanisms for cardiovascular death have not been fully investigated. We examined electropharmacological effects of azithromycin in intravenous doses of 0.3, 3 and 30 mg/kg using microminipigs under the halothane anesthesia (n = 4), which provided plasma concentrations of 3.1, 11.2 and 120.4 μg/mL, respectively. The low dose did not alter any of the cardiohemodynamic or electrocardiographic variables. The middle dose significantly shortened QT interval for 10-20 min and QTc for 10-30 min...
October 17, 2018: Journal of Pharmacological Sciences
Naoto Iizuka, Akane Morita, Chihiro Kawano, Asami Mori, Kenji Sakamoto, Masakazu Kuroyama, Kunio Ishii, Tsutomu Nakahara
Pathological retinal angiogenesis contributes to the pathogenesis of several ocular diseases. Valproic acid, a widely used antiepileptic drug, exerts anti-angiogenic effects by inhibiting histone deacetylase (HDAC). Herein, we investigated the effects of valproic acid and vorinostat, a HDAC inhibitor, on pathological retinal angiogenesis in mice with oxygen-induced retinopathy (OIR). OIR was induced in neonatal mice by exposure to 80% oxygen from postnatal day (P) 7 to P10 and to atmospheric oxygen from P10 to P15...
October 14, 2018: Journal of Pharmacological Sciences
Yan-Ling Liu, Chun-Yan Kong, Peng Song, Heng Zhou, Xing-Sheng Zhao, Qi-Zhu Tang
Cardiac hypertrophy is characterized by myocyte hypertrophy, accumulation of cardiac collagen, and reactivation of fetal genes. Maslinic acid (MA) is a pentacyclic triterpene with abundance in olive fruit skin and possesses a number of pharmacological actions. However, its effect on pressure overload-induced cardiac hypertrophy remains unknown. Here, we were to investigate the protective effect of MA on cardiac hypertrophy and fibrosis. C57 mice were subjected to aortic banding (AB) or sham surgery. One day after surgery, all the mice were orally given MA (20 mg/kg) or vehicle for the following four weeks...
October 14, 2018: Journal of Pharmacological Sciences
Yoshikazu Mikami, Daisuke Omagari, Yusuke Mizutani, Manabu Hayatsu, Tatsuo Ushiki, Hiromasa Tsuda
Inorganic polyphosphate (polyP), a linear polymer of orthophosphate, is found at high concentrations in osteoblasts. We demonstrated the effects of various polyP concentrations on the mineralization of rat osteoblast ROS17/2.8 cells. Mineralization of ROS17/2.8 was induced by a high polyP concentration (1 mg/mL), which was accompanied by an upregulation of the bone sialoprotein and osteocalcin. In contrast, a low polyP concentration (1 × 10-2  mg/mL) reduced mineralization without affecting the osteogenic gene expression...
October 13, 2018: Journal of Pharmacological Sciences
Yuka Nakamura, Yoshihisa Kitamura, Yusuke Sumiyoshi, Nanami Naito, Shiho Kan, Soichiro Ushio, Ikuko Miyazaki, Masato Asanuma, Toshiaki Sendo
We examined whether combination treatment with doxorubicin and cyclophosphamide, a traditional chemotherapy for breast cancer, induced anxiety-like behavior in rats. Furthermore, we evaluated the role of the serotonin (5-HT)2A receptor subtype in the anxiety-like behavior induced by such chemotherapy. Rats were intraperitoneally injected with doxorubicin and cyclophosphamide once a week for 2 weeks. This caused the rats to display anxiety-like behavior during the light-dark test. In addition, we examined the rats' 5-HT2A receptor-mediated behavioral responses...
October 9, 2018: Journal of Pharmacological Sciences
Lu Liu, Xin Huang, Jinliao Gao, Yusong Guo, Yanqi Di, Shasha Sun, Xinli Deng, Jian Cao
Metabolic syndrome (MS) is a combination of symptoms characterized by central obesity, hypertension, hyperglycemia, and hyperlipidemia, which together increase the risk of heart disease, stroke and diabetes. In our study, we hypothesized that an EET-agonist (AUDA) would increase expression of PGC 1α and improve mitochondrial and endothelial functions, resulting in improved heart function in a rat model of MS. To investigate this, rats were randomly divided into four groups: 1) Control; 2) MS + ABCT; 3) MS + AUDA; and 4) MS + AUDA + SnMP...
October 4, 2018: Journal of Pharmacological Sciences
Zhenhua Fei, Wenyue Gu, Raoying Xie, Huafang Su, Yiyan Jiang
Radiotherapy plays an important therapeutic role in esophageal cancer (EC). However, acquired radioresistance impairs the efficacy of radiotherapy, often leading to treatment failure. Therefore, it is important to develop novel radiosensitizers to enhance the clinical treatment of EC. The purpose of this study was to investigate the role of artesunate (ART) on radiosensitivity of human EC cell line TE-1. We found that ART inhibited the proliferation of EC cells and enhanced the radiosensitivity of TE-1 cells (SER = 1...
September 29, 2018: Journal of Pharmacological Sciences
Jiadai Liu, Elena G Rybakina, Eelena A Korneva, Mami Noda
Sodium salt of deoxyribonucleic acid (DNA), Derinat, isolated from the soft roes of Russian sturgeon, has been utilized as an immunomodulator for the treatment of reactive oxygen species (ROS)-associated diseases in clinics. Here we show that treatment with Derinat has an anti-inflammatory and anti-oxidative effects on cutaneous ischemia-reperfusion (IR) injury in pressure ulcer (PU) model mice. Dorsal skin damage and dermal edema in mild PU model mice were attenuated by treatment with Derinat. Immunohistochemical and biochemical analyses showed that Derinat suppressed IR-induced oxidative damage, i...
September 27, 2018: Journal of Pharmacological Sciences
Akiyoshi Saitoh, Akinobu Soda, Shuhei Kayashima, Kazumi Yoshizawa, Jun-Ichiro Oka, Hiroshi Nagase, Mitsuhiko Yamada
We previously reported that systemic administration of a delta opioid receptor (DOP) agonist, KNT-127, produced a potent anxiolytic-like effect in rats. Interestingly, DOPs are highly distributed in the prelimbic medial prefrontal cortex (PL-PFC). In the present study, we investigated the effect of KNT-127 co-perfusion in the PL-PFC on anxiety-like behavior in mice, induced by a glial glutamate transporter inhibitor, (3S)-3-[[3-[[4-(Trifluoromethyl)benzoyl]amino]phenyl]methoxy]-l-aspartic acid (TFB-TBOA). Extracellular glutamate levels were measured in male C57BL/6N mice by in vivo microdialysis high-performance liquid chromatography/electrochemical detection, with behavior simultaneously assessed in the open field test...
September 27, 2018: Journal of Pharmacological Sciences
Warisara Parichatikanond, Akiyuki Nishimura, Motohiro Nishida, Supachoke Mangmool
Insulin resistance is a condition in which there is a defect in insulin actions to induce glucose uptake into the cells. Overstimulation of β2 -adrenergic receptors (β2 ARs) is associated with the pathogenesis of insulin resistance in the heart. However, the mechanisms by which β2 -agonists affect insulin resistance in the heart are incompletely understood. The β2 -agonists are used for treatment of asthma due to bronchodilating effects. We also investigated the effects of β2 -agonists in human bronchial smooth muscle (HBSM) cells...
September 26, 2018: Journal of Pharmacological Sciences
Cuili Zou, Qiaoqin Zhang, Shenghong Zhang
As one kind of complications of pregnancy, gestational diabetes mellitus (GDM) can influence the health of maternal-child in clinical practice. The C57 BL/KsJdb/+ (db/+) mice, genetic GDM model, and C57 BL/KsJ+/+ (wild-type) mice were purchased and classified into three groups: normal pregnancy (C57 BL/KsJ+/+ ), GDM (C57 BL/KsJdb/+ ), and GDM plus Mogroside IIIE (20.0 mg/kg) group. GDM symptoms (maternal body weight, serum glucose, and insulin levels), glucose and insulin tolerance, and reproductive outcome (body weight at birth and litter size of offspring) were investigated...
September 26, 2018: Journal of Pharmacological Sciences
Satoshi Deyama, Kento Shimoda, Hiroyuki Ikeda, Hayato Fukuda, Satoshi Shuto, Masabumi Minami
Eicosapentaenoic acid (EPA)-derived resolvin E1 (RvE1) and E2 (RvE2) have antidepressant effects. Here, we investigated the antidepressant effects of resolvin E3 (RvE3) in a mouse model of lipopolysaccharide (LPS)-induced depression. We observed that LPS (0.8 mg/kg, i.p.) significantly increased immobility time on the tail suspension test, and this depression-like behavior was dose-dependently attenuated by intracerebroventricular infusion of RvE3 (10 or 100 ng). No effects of LPS or intracerebroventricular infusion of RvE3 on locomotor activity were observed...
September 26, 2018: Journal of Pharmacological Sciences
Ming Ni, Jigang Zhang, Lin Huang, Gaolin Liu, Qin Li
The current study investigated whether a Rho-kinase inhibitor alleviated impairments in a rat model of chronic cerebral ischemia and examined the specific pathological mechanisms by which Rho-kinase impacts neuronal damage and cognitive dysfunction. Adult Sprague-Dawley rats underwent permanent bilateral carotid artery occlusion (BCAO) to establish our chronic cerebral ischemia model. Chronic Y27632 administration reversed the abnormal behaviors of BCAO-treated rats in the Morris water maze. We performed Western blot analyses of the apoptosis-related proteins Bcl-2 and Bax to examine the potential mechanism underlying the beneficial effects of Y27632 on cerebral ischemia and showed for the first time that Y27632 reversed the decrease in the Bcl-2/Bax ratio in BCAO model rats...
September 22, 2018: Journal of Pharmacological Sciences
Tian-Yi Zhou, Yu-Lu Zhou, Mei-Jia Qian, Yi-Zheng Fang, Song Ye, Wen-Xiu Xin, Xiao-Chun Yang, Hong-Hai Wu
Tumor-associated macrophages (TAMs) has been regarded as the most prominent component in tumor microenvironment. The correlation between TAM density and poor prognosis in Hepatocellular carcinoma (HCC) patients suggests a supportive role for TAMs in tumor progression. Here we employed a co-culture system to interrogate the molecular link between Yes-Associated Protein (YAP) and TAMs chemotaxis in HCC cells. We found that YAP activation was critical for the recruitment of TAMs towards HCC cells. Furthermore, cytokine array and quantitative RT-PCR analyses showed that IL-6 secreted by YAP-activated HCC cells might induce the TAMs recruitment...
September 22, 2018: Journal of Pharmacological Sciences
Yuki Kurauchi, Kazuki Noma, Akinori Hisatsune, Takahiro Seki, Hiroshi Katsuki
Na+ , K+ -ATPase is a highly expressed membrane protein. Dysfunction of Na+ , K+ -ATPase has been implicated in the pathophysiology of several neurodegenerative and psychiatric disorders, however, the underlying mechanism of neuronal cell death resulting from Na+ , K+ -ATPase dysfunction is poorly understood. Here, we investigated the mechanism of neurotoxicity due to Na+ , K+ -ATPase inhibition using rat organotypic hippocampal slice cultures. Treatment with ouabain, a Na+ , K+ -ATPase inhibitor, increased the ratio of propidium iodide-positive cells among NeuN-positive cells in the hippocampal CA1 region, which was prevented by MK-801 and d-AP5, specific blockers of the N-methyl-d-aspartate (NMDA) receptor...
September 22, 2018: Journal of Pharmacological Sciences
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