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Journal of Pharmacological Sciences

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https://www.readbyqxmd.com/read/28928055/electrophysiological-analyses-of-transgenic-mice-overexpressing-kcnj8-with-s422l-mutation-in-cardiomyocytes
#1
Yasuhiro Watanabe, Akio Matsumoto, Takashi Miki, Susumu Seino, Naohiko Anzai, Haruaki Nakaya
Genetic analysis of KCNJ8 has pointed a mutation (S422L) as a susceptible link to J wave syndrome (JWS). In vitro expression study indicated that the ATP-sensitive K(+) (KATP) channel with the S422L mutation has the gain-of-function with reduced sensitivity to ATP. However, the electrophysiological impact of KCNJ8 has not been elucidated in vivo. Transgenic mouse strains overexpressing KCNJ8 S422L variant (TGmt) or WT (TGWT) in cardiomyocytes have been created to investigate the influence of KCNJ8 in cardiomyocytes and the JWS-related feature of the S422L variant on the cardiac electrophysiology...
September 6, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28928053/development-of-correction-formula-for-field-potential-duration-of-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-sheets
#2
Hiroko Izumi-Nakaseko, Yasunari Kanda, Yuji Nakamura, Mihoko Hagiwara-Nagasawa, Takeshi Wada, Kentaro Ando, Atsuhiko T Naito, Yuko Sekino, Atsushi Sugiyama
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been used in many studies to assess proarrhythmic risks of chemical compounds. In those studies, field potential durations (FPD) of hiPSC-CMs have been corrected by clinically used Fridericia's and/or Bazett's formulae, however, the rationale for the use of these formulae has not been well established. In the present study, we developed a correction formula for experiments using hiPSC-CMs. First, we analyzed the effect of beating rate on FPD in the hiPSC-CMs sheets with electrical stimuli and a HCN channel inhibitor zatebradine...
September 6, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28927781/function-of-38-variants-cyp2c9-polymorphism-on-ketamine-metabolism-in%C3%A2-vitro
#3
Xiang Zheng, Ping Fang, Su-Su Bao, Dan Lin, Jian-Ping Cai, Guo-Xin Hu
BACKGROUND: Cytochrome P450 proteins (CYP 450) is the most important enzyme system of drug phase I metabolism in liver. In previous reports, reduced efficiency or increased risk of adverse events can be affected by primary sequence mutation in CYP450. AIM: To investigate the effect of gene polymorphism on the metabolism of ketamine in vitro, including the new alleles: 2C9*58, *59 and *60. METHOD: Incubation system which was contained insect microsome, b5, NADPH and 1M PBS incubated 10 μM-1000 μM ketamine in 37 °C for 40 min concentration of norketamine was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry system (UPLC-MS/MS)...
September 1, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28928054/effect-of-the-antidiabetic-agent-pioglitazone-on-bone-metabolism-in-rats
#4
Junkichi Kanda, Nobuo Izumo, Yoshiko Kobayashi, Kenji Onodera, Taketoshi Shimakura, Noriaki Yamamoto, Hideaki E Takahashi, Hiroyuki Wakabayashi
Thiazolidinediones (TZDs) are synthetic peroxisome proliferator-activated receptor gamma (PPARγ) agonists used as therapy for type 2 diabetes. However, clinical studies reported that the therapeutic modulation of PPARγ activity using TZDs may induce negative effects on bone metabolism. This study aimed to evaluate the effect of the TZD pioglitazone on bone metabolism in rats. Male Wistar rats were treated orally with pioglitazone 5 or 20 mg/kg daily for 24 weeks. Bone strength was evaluated using a 3-point bending method, and bone histomorphometry was analyzed...
August 26, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28923269/dpp-4-inhibition-protects-human-umbilical-vein-endothelial-cells-from-hypoxia-induced-vascular-barrier-impairment
#5
Naoko Hashimoto, Kento Ikuma, Yui Konno, Masanori Hirose, Hiroyuki Tadokoro, Hiroshi Hasegawa, Yoshio Kobayashi, Hiroyuki Takano
Dipeptidyl peptidase-4 (DPP-4) inhibitors are relatively new class of anti-diabetic drugs. Some protective effects of DPP-4 on cardiovascular disease have been described independently from glucose-lowering effect. However, the detailed mechanisms by which DPP-4 inhibitors exert on endothelial cells remain elusive. The purpose of this research was to determine the effects of DPP-4 inhibitor on endothelial barrier function. Human umbilical vein endothelial cells (HUVECs) were cultured and exposed to hypoxia in the presence or absence of Diprotin A, a DPP-4 inhibitor...
August 26, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28927780/effects-of-metformin-on-proliferation-and-apoptosis-of-human-megakaryoblastic-dami-and-meg-01-cells
#6
Xue Liang, Peiyan Kong, Jin Wang, Yulin Xu, Chunfang Gao, Guozhen Guo
Metformin has received increasing attention for its potential anticancer activity against certain human leukemia cells, but its effects on human megakaryoblastic cells are unclear. This study aimed to investigate the effects of metformin on proliferation and apoptosis of human megakaryoblastic cells (Dami and MEG-01) and the underlying molecular mechanisms. CCK8 assay was employed to measure cell proliferation. Flow cytometry was adopted to detect cell apoptosis. Western blot was further employed to measure apoptosis-related proteins...
August 23, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28757172/polyphyllin-vii-increases-sensitivity-to-gefitinib-by-modulating-the-elevation-of-p21-in-acquired-gefitinib-resistant-non-small-cell-lung-cancer
#7
Honggang Wang, Zhenghua Fei, Hao Jiang
Blockade of EGFR with reversible EGFR tyrosine kinase inhibitors (TKIs) is considered the frontline strategy for advanced NSCLC with EGFR mutations. However, acquired resistance to EGFR-TKI has been observed, resulting in disease progression and limited clinical benefit. Polyphyllin VII is the main member of polyphyllin family, which has been demonstrated to show strong anticancer activity against carcinomas. The sensitizing effect and underlying mechanism of Polyphyllin VII against acquired EGFR-TKI resistant NSCLC are still unexplored...
June 30, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28694090/milnacipran-affects-mouse-impulsive-aggressive-and-depressive-like-behaviors-in-a-distinct-dose-dependent-manner
#8
Iku Tsutsui-Kimura, Yu Ohmura, Takayuki Yoshida, Mitsuhiro Yoshioka
Serotonin/noradrenaline reuptake inhibitors (SNRIs) are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg), an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, resident-intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively...
June 27, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28844424/analysis-of-proarrhythmic-potential-of-an-atypical-antipsychotic-drug-paliperidone-in-the-halothane-anesthetized-dogs
#9
Koki Chiba, Takeshi Wada, Yuji Nakamura, Xin Cao, Mihoko Hagiwara-Nagasawa, Hiroko Izumi-Nakaseko, Kentaro Ando, Koichiro Tanaka, Atsuhiko T Naito, Atsushi Sugiyama
Fatal cases with the use of atypical antipsychotic drug paliperidone have been reported; however, there was no clinical report describing paliperidone-induced torsade de pointes. In this study we assessed its electropharmacological effects together with its proarrhythmic potential in intravenous doses of 0.03, 0.3 and 3 mg/kg using the halothane-anesthetized dogs (n = 5), which could provide approximately 2, 20 and 200 times higher peak plasma drug concentrations than its therapeutic level, respectively...
August 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28844423/dosing-time-dependent-effect-of-rivaroxaban-on-coagulation-activity-in-rats
#10
Yuki Fujiwara, Hitoshi Ando, Kentaro Ushijima, Michiko Horiguchi, Chikamasa Yamashita, Akio Fujimura
The anticoagulant effect of rivaroxaban, a direct inhibitor of activated factor X (FX), might be influenced by its dosing time because the activity of the coagulofibrinolytic system exhibits daily rhythmicity. In rats, FX activity follows a 24-h rhythm with a peak in the middle of the light phase and a trough at the beginning of the dark phase. Consistent with these findings, a single dose of rivaroxaban had a stronger inhibitory effect on FX activity after dosing at the beginning of the light phase than after dosing at the beginning of the dark phase...
August 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28844422/dietary-supplementation-with-essence-of-chicken-enhances-daily-oscillations-in-plasma-glucocorticoid-levels-and-behavioral-adaptation-to-the-phase-shifted-environmental-light-dark-cycle-in-mice
#11
Adila Dilixiati, Satoru Koyanagi, Naoki Kusunose, Naoya Matsunaga, Shigehiro Ohdo
Maintenance of circadian rhythms is essential to many aspects of human health, including metabolism and neurological and psychiatric well-being. Chronic disruption of circadian clock function is implicated in increasing the risk of metabolic syndrome, cardiovascular events and development of cancers. However, there are little approaches to reinforce the function of circadian clock for prevention of these diseases. Essence of Chicken (EC) is a nutritional supplement that is traditionally made by extracting water soluble substances derived from cooking the whole chicken...
August 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28843667/the-specific-localization-of-advanced-glycation-end-products-ages-in-rat-pancreatic-islets
#12
Yuta Morioka, Kiyoshi Teshigawara, Yasuko Tomono, Dengli Wang, Yasuhisa Izushi, Hidenori Wake, Keyue Liu, Hideo Kohka Takahashi, Shuji Mori, Masahiro Nishibori
Advanced glycation end-products (AGEs) are produced by non-enzymatic glycation between protein and reducing sugar such as glucose. Although glyceraldehyde-derived AGEs (Glycer-AGEs), one of the AGEs subspecies, have been reported to be involved in the pathogenesis of various age-relating diseases such as diabetes mellitus or arteriosclerosis, little is known about the pathological and physiological mechanism of AGEs in vivo. In present study, we produced 4 kinds of polyclonal antibodies against AGEs subspecies and investigated the localization of AGEs-modified proteins in rat peripheral tissues, making use of these antibodies...
August 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28826625/preventive-effect-of-curcumin-and-its-highly-bioavailable-preparation-on-hearing-loss-induced-by-single-or-repeated-exposure-to-noise-a%C3%A2-comparative-and-mechanistic-study
#13
Taro Yamaguchi, Masanori Yoneyama, Yusuke Onaka, Atsushi Imaizumi, Kiyokazu Ogita
We sought to determine the preventive effects of curcumin and its highly bioavailable preparation on noise-induced hearing loss in a novel murine model of permanent hearing loss developed by repeated exposure to noise. Upon exposure to noise (8-kHz octave band noise, 90 dB sound pressure level, 1 h), hearing ability was impaired in a temporary and reversible manner. During repeated noise exposure (1-h exposure per day, 5 days), there was a progressive increase in the auditory threshold shift at 12 and 20 kHz...
August 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28779994/the-iron-chelating-agent-deferoxamine-detoxifies-fe-salen-induced-cytotoxicity
#14
Masanari Umemura, Jeong-Hwan Kim, Haruki Aoyama, Yujiro Hoshino, Hidenobu Fukumura, Rina Nakakaji, Itaru Sato, Makoto Ohtake, Taisuke Akimoto, Masatoshi Narikawa, Ryo Tanaka, Takayuki Fujita, Utako Yokoyama, Masataka Taguri, Satoshi Okumura, Motohiko Sato, Haruki Eguchi, Yoshihiro Ishikawa
Iron-salen, i.e., μ-oxo-N,N'-bis(salicylidene)ethylenediamine iron (Fe(Salen)) was a recently identified as a new anti-cancer compound with intrinsic magnetic properties. Chelation therapy has been widely used in management of metallic poisoning, because an administration of agents that bind metals can prevent potential lethal effects of particular metal. In this study, we confirmed the therapeutic effect of deferoxamine mesylate (DFO) chelation against Fe(Salen) as part of the chelator antidote efficacy. DFO administration resulted in reduced cytotoxicity and ROS generation by Fe(Salen) in cancer cells...
August 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28779993/the-class-i-pi3k-inhibitor-s14161-induces-autophagy-in-malignant-blood-cells-by-modulating-the-beclin-1-vps34-complex
#15
Siyu Wang, Jie Li, Yanyun Du, Yujia Xu, Yali Wang, Zubin Zhang, Zhuan Xu, Yuanying Zeng, Xinliang Mao, Biyin Cao
S14161 is a pan-Class I PI3K inhibitor that induces blood cancer cell death, but its mechanism is largely unknown. In the present study, we evaluated the role of S14161 in autophagy, an emerging event in cell destination. Multiple myeloma cell lines RPMI-8226, OPM2, KMS11 and leukemia cell line K562 were treated with S14161. The results showed that S14161 induced autophagy as demonstrated by increased LC3-II and decreased p62, which were prevented by autophagy inhibitors including 3-methyladenine and bafilomycin A1...
August 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28689962/astaxanthin-analogs-adonixanthin-and-lycopene-activate-nrf2-to-prevent-light-induced-photoreceptor-degeneration
#16
Yuki Inoue, Masamitsu Shimazawa, Ryota Nagano, Yoshiki Kuse, Kei Takahashi, Kazuhiro Tsuruma, Masahiro Hayashi, Takashi Ishibashi, Takashi Maoka, Hideaki Hara
Carotenoids, in particular astaxanthin, possess potent antioxidant capabilities. Astaxanthin also induces NF-E2-related factor 2 (Nrf2), which plays a major regulatory role in the antioxidative response. However, little is known whether the carotenoid, by-products of astaxanthin, activate Nrf2. Toward this end, we screened eight astaxanthin analogs for Nrf2 activation in murine photoreceptor cell line, 661 W, by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In addition, we monitored cell death in 661 W cells pretreated with astaxanthin analogs or only pretreated for 6 h with astaxanthin analogs and then exposed to light...
June 21, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28669596/role-of-microglia-in-mechanical-allodynia-in-the-anterior-cingulate-cortex
#17
Keisuke Miyamoto, Kazuhiko Kume, Masahiro Ohsawa
Plastic changes that increase nociceptive transmission are observed in several brain regions under conditions of chronic pain. Synaptic plasticity in the anterior cingulate cortex (ACC) is particularly associated with neuropathic pain. Glial cells are considered candidates for the modulation of neural plastic changes in the central nervous system. In this study, we aimed to investigate the role of ACC glial cells in the development of neuropathic pain. First, we examined the expression of glial cells in the ACC of nerve-ligated mice...
June 21, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28689961/pregabalin-reduces-cisplatin-induced-mechanical-allodynia-in-rats
#18
Yoshihiro Seto, Miyuki Takase, Yasuhiro Tsuji, Hideto To
Although cisplatin (CDDP) is a key drug in cancer chemotherapy, CDDP-induced peripheral neuropathy is a dose-limiting factor. We previously reported that CDDP-induced peripheral neuropathy, which progressed from allodynia to hypoalgesia, was ameliorated by the administration of CDDP to rats at a specific time. However, mechanical allodynia cannot be prevented therapeutically. Pregabalin (PGN) is used to suppress neuropathic pain from herpes zoster and diabetes. Therefore, we investigated the effects of PGN on CDDP-induced mechanical allodynia in rats...
June 20, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28673635/chymase-inhibitor-prevents-the-development-and-progression-of%C3%A2-non-alcoholic-steatohepatitis-in-rats-fed-a-high-fat-and-high-cholesterol-diet
#19
Yuta Miyaoka, Denan Jin, Keitaro Tashiro, Koji Komeda, Shinsuke Masubuchi, Fumitoshi Hirokawa, Michihiro Hayashi, Shinji Takai, Kazuhisa Uchiyama
The effect of the chymase inhibitor TY-51469 on the development and progression of non-alcoholic steatohepatitis (NASH) was evaluated in rats fed a high-fat and high-cholesterol (HFC) diet. To evaluate the preventive effect of TY-51469 on the development of NASH, stroke-prone spontaneously hypertensive rat 5 (SHRSP5)/Dmcr rats were fed either a normal or HFC diet for 8 weeks, and concurrently administered either placebo or TY-51469 (1 mg/kg per day). To evaluate the effect of TY-51469 on the survival rate, TY-51469 was administered either concurrently with HFC diet (pretreated group) or 8 weeks after HFC diet at which point NASH had developed (posttreated group)...
June 20, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28669597/local-intra-articular-injection-of-resveratrol-delays-cartilage-degeneration-in-c57bl-6-mice-by-inducing-autophagy-via-ampk-mtor-pathway
#20
Na Qin, Liwei Wei, Wuyin Li, Wei Yang, Litao Cai, Zhuang Qian, Shufang Wu
Autophagy is an essential cellular homeostasis mechanism that was found to be compromised in aging and osteoarthritis (OA) cartilage. Previous studies showed that resveratrol can effectively regulate autophagy in other cells. The purpose of this study was to determine whether the chondroprotective effect of resveratrol was related to chondrocyte autophagy and to elucidate underlying mechanisms. OA model was induced by destabilization of the medial meniscus (DMM) in 10-week-old male mice. OA mice were treated with resveratrol with/without 3-MA for 8 weeks beginning 4 weeks after surgery...
June 15, 2017: Journal of Pharmacological Sciences
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