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Atsuki Yamamoto, Tomokazu Itoh, Reishi Nasu, Eiji Kajiwara, Ryuichi Ni ...
2013 Volume 36 Issue 10 Pages
1528-1534
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
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Gastrointestinal mucositis is one of the most prevalent side effects of chemotherapy. Methotrexate is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. Through its effects on normal tissues with high rates of proliferation, methotrexate treatment leads to gastrointestinal mucositis. In rats, methotrexate-induced gastrointestinal mucositis is histologically characterized by crypt loss, callus fusion and atrophy, capillary dilatation, and infiltration of mixed inflammatory cells. The water-soluble dietary fiber sodium alginate (AL-Na) is derived from seaweed and has demonstrated muco-protective and hemostatic effects on upper gastrointestinal ulcers. In the present study, we evaluated the effects of AL-Na on methotrexate-induced small intestinal mucositis in rats. Animals were subcutaneously administered methotrexate at a dosage of 2.5 mg/kg once daily for 3 d. Rats were treated with single oral doses of AL-Na 30 min before and 6 h after methotrexate administration. On the 4th day, small intestines were removed and weighed. Subsequently, tissues were stained with hematoxylin–eosin and bromodeoxyuridine. AL-Na significantly prevented methotrexate-induced small intestinal mucositis. Moreover, AL-Na prevented decreases in red blood cell numbers, hemoglobin levels, and hematocrit levels. These results suggest the potential of AL-Na as a therapy for methotrexate-induced small intestinal mucositis.
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Joohee Jung, Ki Hwan Bae, Choon-Sik Jeong
2013 Volume 36 Issue 10 Pages
1535-1539
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
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Supplementary material
In this study, we evaluated the gastric protective activities of mokdanpi
in vitro. Further, we used experimental ulcer models to identify the active ingredients of mokdanpi. As a preliminary evaluation of mokdanpi ethanolic extract and its ingredients, we assessed its radical scavenging activities. In addition, its antimicrobial activity against
Helicobacter pylori (
H. pylori) was investigated. The antiulcerogenic activity of the active ingredients was evaluated in pylorus-ligated rats, an HCl/ethanol-induced and an absolute ethanol-induced ulcer model. We confirmed the scavenging effect of the ethanolic extract of mokdanpi and its ingredients against 2,2-diphenyl-1-picrylhydrazyl, nitric oxide and superoxide radicals, and we demonstrated that mokdanpi could inhibit the colonization of
H. pylori. In an HCl–ethanol-induced ulcer model, gallic acid and catechin (100 mg/kg) inhibited 40.6% and 41.7% of gastric lesions, respectively. Catechin (100 mg/kg) significantly reduced (
p<0.05) the gastric secretion induced by pylorus ligature in rats in comparison to the control group. Gallic acid (100 mg/kg) significantly increased (
p<0.05) the mucus contents in an ethanol-induced ulcer model. The antioxidant ingredients (catechin and gallic acid) present in mokdanpi play a major role in antiulcerogenic activity, and demonstrate novel activity against
H. pylori.
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Pengyi Deng, Chen Wang, Liulin Chen, Cheng Wang, Yuhan Du, Xu Yan, Min ...
2013 Volume 36 Issue 10 Pages
1540-1548
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
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Sesamin, one of the most abundant lignans in sesame seeds, has been shown to exhibit various pharmacological effects. The aim of this study was to elucidate whether sesamin promotes cell cycle arrest and induces apoptosis in HepG2 cells and further to explore the underlying molecular mechanisms. Here, we found that sesamin inhibited HepG2 cell growth by inducing G2/M phase arrest and apoptosis. Furthermore, sesamin suppressed the constitutive and interleukin (IL)-6-induced signal transducer and activator of transcription 3 (STAT3) signalling pathway in HepG2 cells, leading to regulate the downstream genes, including p53, p21, cyclin proteins and the Bcl-2 protein family. Our studies showed that STAT3 signalling played a key role in sesamin-induced G2/M phase arrest and apoptosis in HepG2 cells. These findings provided a molecular basis for understanding of the effects of sesamin in hepatocellular carcinoma tumour cell proliferation. Therefore, sesamin may thus be a potential chemotherapy drug for liver cancer.
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Changwu Xu, Jing Chen, Jing Zhang, Xiaorong Hu, Xiaoya Zhou, Zhibing L ...
2013 Volume 36 Issue 10 Pages
1549-1555
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
Advance online publication: August 03, 2013
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Proliferation and migration of vascular smooth muscle cells (VSMCs) play pivotal roles in the development of restenosis after angioplasty and oxidative stress involves both processes. Naringenin, a flavanone compound found in citrus fruits, has been widely evaluated for antioxidant activity. This study was designed to explore whether naringenin could inhibit angiotensin II-induced VSMCs proliferation and migration and decrease neointimal hyperplasia in balloon injured rat carotid arteries. VSMCs were treated with or without naringenin before stimulation with 1 µ
M angiotensin II and twenty-four rats were subjected to carotid arteries injury and the carotid arteries were harvested at 14 d after balloon injury. The results showed naringenin led to a significant inhibition of angiotensin II-induced VSMCs proliferation and migration. Naringenin significantly attenuated the reactive oxygen species production, increased the superoxide dismutase activity and decreased the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, reduced phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) and the nuclear translocation of nuclear factor (NF)-κB p65 in angiotensin II-treated VSMCs. Moreover, naringenin decreased the ratio of neointima to media by 63.8% in balloon injured rat carotid arteries, and the serum level of 8-
iso-prostaglandin F2α in naringenin-treated rats was significantly decreased. These results indicated naringenin exhibited antioxidant activity on angiotensin II-treated VSMCs and balloon injured rat carotid arteries and could be a potential protective agent for restenosis after angioplasty.
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Hyo Geun Kim, Tae-mi Kim, Gunhyuk Park, Tae Hee Lee, Myung Sook Oh
2013 Volume 36 Issue 10 Pages
1556-1561
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
Advance online publication: July 10, 2013
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Environmental heat stress is associated with physical stress responses, including changes in monoamines, protein expression, and neuronal circuits and damage to neurons in the brain. This study determined the effects of heat stress on the nigrostriatal dopaminergic system based on behavioral, histological, and neurochemical analyses. To evaluate behavioral changes after heat exposure, we subjected mice to the pole and open field tests. The data suggested that heat stress for 7 d significantly impaired movement. Then, we conducted a histological analysis using tyrosine hydroxylase (TH) immunoreactivity in the striatum and substantia nigra (SN). Heat stress induced a significant deficit in TH-positive fibers and cells after 14- and 21-d exposure, respectively. We also measured the striatal dopamine (DA), 4-hydroxy-3-methoxy-phenylacetic acid, and 3,4-dihydroxyphenylacetic acid levels. The data suggested that DA turnover rate increased with heat exposure in a time-dependent manner, resulting in the significant decrease of DA after 28 d. Moreover, the expression of heat shock protein 70 (HSP70) was increased in the mouse SN with up to 14-d heat exposure, but decreased after 21 d of the stress. And glucose-regulated protein 78 (GRP78) was gradually increased in the mouse SN with 28-d heat exposure. The caspase-3 activity was also increased after 14-d heat exposure. These findings are the first evidence that repeated heat stress impairs nigrostriatal dopaminergic neurons, motor function, and DA availability with changes of HSP70 and GRP78 expressions and caspase-3 activity in mice.
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Yong-Qiang Shan, Yan-Ping Zhu, Jing Pang, Yan-Xiang Wang, Dan-Qing Son ...
2013 Volume 36 Issue 10 Pages
1562-1569
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
Advance online publication: August 08, 2013
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This study was designed to improve the absorption and hypoglycemic efficacy of berberine (BBR), which is a substrate of P-glycoprotein (P-gp), by combination with a P-gp inhibitor tetrandrine (Tet). Flow cytometry and LC-MS/MS were used to determine the cellular efflux or retention of chemicals. Pharmacokinetic study was performed in ICR mice following oral administration of the study compounds. The hypoglycemic efficacies of the compounds were evaluated in diabetic KK-Ay mice. In the
in vitro experiments, Tet significantly inhibited the efflux and increased the uptake of P-gp substrates rhodamine-123 as well as BBR in MCF7/DOX cells and Caco-2 intestinal cells. Meanwhile, Tet greatly reduced the expression of P-gp in Caco-2 cells. The inhibition of BBR efflux by Tet was translated into improved pharmacokinetics
in vivo. When co-administered, Tet dose-dependently increased the average maximum concentration (
Cmax) and area under concentration–time curve (
AUC0–24) of BBR in mice. Tet itself had no impact on glucose metabolism. However, it greatly potentiated the hypoglycemic efficacy of BBR in diabetic KK-Ay mice. In addition, we found that Tet had moderate inhibitory effect on the catalytic activity of CYP3A4, which played a role in the bio-transformation of BBR, and this may also take part in the improvement of the pharmacokinetics of BBR. In summary, combination with P-gp inhibitors such as Tet can improve the pharmacokinetics and hypoglycemic efficacy of BBR greatly; this implicates a feasible strategy for exploring the therapeutic effects of BBR and other pharmaceuticals which are substrates of P-gp.
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Gwanpyo Koh, Eun-Jin Yang, Min-Kyoung Kim, Sang Ah Lee, Dae-Ho Lee
2013 Volume 36 Issue 10 Pages
1570-1576
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
Advance online publication: August 03, 2013
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Supplementary material
We investigated whether α-lipoic acid (LA) could prevent 2-deoxy-
D-ribose (dRib)-induced oxidative damage and suppression of insulin expression in pancreatic β-cells. Stimulation with 50 m
M dRib elevated cytotoxicity, apoptosis and intracellular reactive oxygen species (ROS) levels in HIT-T15 cells, but pretreatment with LA significantly reversed the dRib-induced changes. LA directly scavenged hydroxyl radicals generated by a Fenton reaction. Intracellular reduced glutathione (GSH) and oxidized glutathione (GSSG) were depleted by stimulation with dRib but levels were restored by addition of LA to HIT-T15 cells. However, the GSH/GSSG ratio was unchanged by LA treatment. In rat islets, stimulation with 10 m
M dRib for 6 h suppressed expression of insulin and pancreatic and duodenal homeobox 1 mRNA and decreased insulin content, but these were dose-dependently reversed when LA was added. Treatment with l-buthionine-sulfoximine, an inhibitor of intracellular glutathione biosynthesis, completely abolished the protective effects of LA on dRib-mediated glutathione depletion and cytotoxicity in HIT-T15 cells. In summary, LA reversed the dRib-induced oxidative damage and suppression of insulin expression in β-cells. Enhanced intracellular total glutathione production, rather than the scavenging of ROS, is possibly the mechanism for the protective effect of LA.
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Yukihiro Oritani, Yuko Setoguchi, Ryouichi Ito, Hiroko Maruki-Uchida, ...
2013 Volume 36 Issue 10 Pages
1577-1582
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
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(−)-Epigallocatechin-3-
O-(3-
O-methyl)gallate (EGCG3″Me) and (−)-epigallocatechin-3-
O-(4-
O-methyl)gallate (EGCG4″Me) are
O-methyl derivatives of (−)-epigallocatechin-3-
O-gallate (EGCG) present in tea cultivars such as Benifuuki. Although
O-methyl EGCGs have various bioactivities, their bioavailabilities have not been determined. In this study, we compared the bioavailability of EGCG and
O-methyl EGCGs in rats, and clarified the pharmacokinetics of
O-methyl EGCGs. Following oral administration (100 mg/kg), the areas under the concentration–time curves (
AUCs) for EGCG, EGCG3″Me, and EGCG4″Me were 39.6±14.2 µg·h/L, 317.2±43.7 µg·h/L, and 51.9±11.0 µg·h/L, respectively. The
AUC after intravenous administration (10 mg/kg) was 2772±480 µg·h/L for EGCG, 8209±549 µg·h/L for EGCG3″Me, and 2465±262 µg·h/L for EGCG4″Me. The bioavailability of EGCG3″Me (0.38%) was the highest (EGCG: 0.14% and EGCG4″Me: 0.21%). The distribution volume of EGCG3″Me (0.26±0.02 L/kg) was the lowest (EGCG: 0.94±0.16 L/kg and EGCG4″Me: 0.93±0.14 L/kg). These results suggested that the higher
AUC of EGCG3″Me after oral administration was related to its high bioavailability and low distribution volume. These findings supported the stronger bioactivity of EGCG3″Me
in vivo.
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Xiaoniu Dai, Yan Liu, Cuifen Wang, Yan Luo, Xiaoqing Li, Zhijun Shen
2013 Volume 36 Issue 10 Pages
1583-1586
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
Advance online publication: July 12, 2013
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We previously reported that 17β-estradiol (E2) improves long term potentiation (LTP) in hippocampal neurons after global ischemia in rat. In the present study, we investigated if E2 can directly modulate the activity of neuronal KCNQ2/3 channels, the molecular entity of neuronal M-current in hippocampus, expressed in the PC-12 cells. We found that exogenous E2 inhibits the KCNQ2/3 channels in a dose-dependent fashion. The minimal inhibitory concentration of E2 is 10 µ
M. At testing membrane potential of +90 mV, the whole cell current density was reduced to 56.5, 49.3 and 31.9% of the control by 50, 20 and 10 µ
M of E2, respectively. The voltage-dependency of the KCNQ2/3 currents was also affected. E2 at 10, 20 and 50 µ
M shifted the half maximal activation voltage (
V1/2) from 13.8±2.3 mV (
n=12) to 20.6±1.9 mV (
n=8,
p<0.05), 26.0±1.9 mV (
n=8,
p<0.001) and 27.6±3.5 mV (
n=8,
p<0.001), respectively. Our data indicate that exogenous E2 can directly affect the activity of KCNQ2/3 channels at pharmacological levels
via a non-genomic pathway.
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Daisuke Ozawa, Takashi Nakamura, Masanori Koike, Kazuya Hirano, Yuichi ...
2013 Volume 36 Issue 10 Pages
1587-1593
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
Advance online publication: August 03, 2013
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Amyloid-beta peptide 1-42 (Aβ42) plays a key role in the neurotoxicity found in Alzheimer’s disease. Mononuclear phagocytes in the brain (microglia), can potentially clear Aβ
via phagocytosis. Recently, the shuttling-protein nucleolin has been shown to possess scavenger receptor-activity. Here, we investigated whether this receptor interacts specifically with Aβ type 1-42 and mediates its phagocytosis by microglia. While monomeric and fibril Aβ42 were phagocytosed by mouse microglial EOC2 cells, amyloid β peptide 1-40 (Aβ40) was only weakly phagocytosed. Surface plasmon-resonance analysis revealed that nucleolin strongly associates with Aβ42, but only weakly associates with Aβ40. Immunofluorescence staining of anti-nucleolin antibody revealed that EOC2 cells and rat primary microglia express nucleolin on their cell surfaces. Further, pretreating EOC2 cells with anti-nucleolin antibody, but not immunoglobulin G (IgG), inhibited phagocytosis of monomeric Aβ42 by microglia. Additionally, nucleolin-transfected HEK293 cells phagocytosed monomeric and fibril Aβ42 but not monomeric and fibril Aβ40. Moreover, AGRO, a nucleolin-specific oligonucleotide aptamer, inhibited phagocytosis of monomeric and fibril Aβ42, but not monomeric and fibril Aβ40. These results indicate that nucleolin is a receptor that allows microglia to recognize monomeric and fibril Aβ42.
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Yoshihisa Kato, Mao Onishi, Koichi Haraguchi, Shinichi Ikushiro, Chiho ...
2013 Volume 36 Issue 10 Pages
1594-1601
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
Advance online publication: July 23, 2013
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The effect of 2,3′,4,4′,5′-pentachlorobiphenyl (CB118) on serum total thyroxine (T
4) level was comparatively examined between C57BL/6 and DBA/2 mice, which are sensitive and insensitive, respectively, to aryl hydrocarbon receptor-mediated biological changes. After 5 d of CB118 administration (50 mg/kg, intraperitoneally (i.p.)), the serum total T
4 levels in both strains of mice were markedly decreased. However, significant decreases in serum thyroid-stimulating hormone levels were observed in DBA/2 mice, but not in C57BL/6 mice. In contrast, significant increases in the level and activity of hepatic T
4-uridine 5′-diphosphate (UDP)-glucuronosyltransferase by CB118 treatment were observed only in C57BL/6 mice. Likewise, significant increases in the amounts of biliary [
125I]T
4 and [
125I]T
4-glucuronide after injection of [
125I]T
4 were observed only in the CB118-pretreated C57BL/6 mice. The CB118-mediated changes in the levels of [
125I]T
4 bound to transthyretin (TTR), albumin, and thyroxine binding globulin (TBG) were also observed in C57BL/6 mice, but not in DBA/2 mice. Despite such strain differences, significant increases in the liver-selective accumulation of [
125I]T
4 by CB118-pretreatment was observed in both C57BL/6 and DBA/2 mice. The present findings indicate that CB118-mediated decreases in levels of serum T
4 in C57BL/6 and DBA/2 mice occur mainly through enhanced accumulation of hepatic T
4.
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Mingming Chang, Xiaohui Li, Yuming Sun, Fang Cheng, Yueqing Li, Weijie ...
2013 Volume 36 Issue 10 Pages
1602-1607
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
Advance online publication: August 08, 2013
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Effective delivery of therapeutic biomolecules across biomembranes is a challenging topic. A cationic cyclopeptide named TD-34 (ACSSKKSKHCG) was reported to improve insulin delivery across biomembranes effectively. Based on our previous work, we investigated the mechanism of TD-34 for enhancing insulin across Caco-2 cell monolayers. Transport studies of insulin, TD-34 and insulin accompanied with TD-34 were performed respectively using Caco-2 cell monolayers at different conditions. Transepithelial electrical resistance (TEER) value was monitored for 24 h immediately after the beginning of transport experiments. Moreover, the tight junction protein (Claudin-1) was localized by confocal immunofluorescence microscopy. Results showed the transport of insulin alone across biomembranes was attributable to multiple routes including passive diffusion. When TD-34 accompanied with or without insulin was treated on Caco-2 cell monolayers, TEER values decreased reversibly, and it was correlated with the reappearance of tight junction proteins by immunostaining assay. It was concluded that the cationic cyclopeptide (TD-34) had the potential to enhance paracellular delivery of insulin across Caco-2 cell monolayers by loosening tight junction reversibly.
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Joan Manjuh Tankam, Michiho Ito
2013 Volume 36 Issue 10 Pages
1608-1614
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
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Supplementary material
The aromatherapeutical potential of
Piper guineense essential oil was investigated in mice
via inhalation administration, and the active compounds were identified. An open field test and light/dark transition test were used to evaluate the sedative and anxiolytic activities of this essential oil, respectively.
P. guineense essential oil showed significant sedative activity at an effective dose of 4.0×10
−5 mg per cage compared to the control group. It also showed potent anxiolytic effect at a dose of 4.0×10
−6 mg per cage. The main compounds of
P. guineense essential oil were linalool (41.8%) and 3,5-dimethoxytoluene (10.9%). These two main compounds were shown to play a major role in the sedative activity of
P. guineense essential oil. These results suggest that inhalation of
P. guineense essential oil might induce a mild tranquilizing effect.
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Nobutomo Ikarashi, Naoki Ogiue, Eri Toyoda, Marina Nakamura, Risako Ko ...
2013 Volume 36 Issue 10 Pages
1615-1621
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
Advance online publication: August 02, 2013
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Aquaporin-3 (AQP3) plays an important role in maintaining the normal water content of the skin. Previously, we revealed that the expression of cutaneous AQP3 increased following oral administration of
Gypsum fibrosum (main component: CaSO
4) to mice. The purpose of this study is to elucidate the mechanism by which
Gypsum fibrosum increases the expression of cutaneous AQP3 in a keratinocyte cell line.
Gypsum fibrosum or CaSO
4 was added to keratinocytes, and the expression level of AQP3, the Ca concentration, the activity of protein kinase C (PKC), and the degrees of phosphorylation of both extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) were measured. The mRNA and protein expression levels of AQP3 increased significantly 6 h-post addition of
Gypsum fibrosum. In keratinocytes treated with
Gypsum fibrosum, increases in the concentration of intracellular Ca, PKC activity, and the phosphorylation of ERK and CREB were observed. Pre-treatment with GF109203X, a PKC inhibitor, suppressed the mRNA expression levels of AQP3. Similarly to treatment with
Gypsum fibrosum, the addition of CaSO
4 led to the same observations in keratinocytes. It is hypothesized that
Gypsum fibrosum causes an increase in the intracellular Ca concentration, PKC activity, and the phosphorylation levels of ERK and CREB, resulting in increased AQP3 expression in keratinocytes. In addition, it is possible that the effect of
Gypsum fibrosum is attributable to CaSO
4, based on the results demonstrating that the mechanisms of action of
Gypsum fibrosum and CaSO
4 were nearly identical.
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Naoto Okada, Kazuyoshi Kawazoe, Kazuhiko Teraoka, Toshihide Kujime, Ma ...
2013 Volume 36 Issue 10 Pages
1622-1626
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
Advance online publication: August 09, 2013
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Denosumab, a fully human monoclonal antibody that inhibits the receptor activator of nuclear factor-κB ligand, inhibits the activation of osteoclasts. Some clinical trials have shown that denosumab suppresses bone resorption in patients with advanced cancer, but hypocalcemia has been reported as a serious adverse effect after the administration of denosumab. It is difficult to predict hypocalcemia in such cases because the risk factors for denosumab-induced hypocalcemia have not been reported. Accordingly, the aim of the present study was to identify the risk factors for hypocalcemia induced by denosumab. We retrospectively reviewed the records of patients who had received denosumab at Tokushima University Hospital between April 2012 and May 2013. Fifty-three patients were analyzed and eleven patients had hypocalcemia after administration of denosumab. Univariate logistic regression analysis revealed that the patients who had not been administered zoledronic acid before receiving denosumab or had lower creatinine clearance (CCr) appeared to have a higher risk of hypocalcemia (
p<0.05). The cut off value of CCr was 50.4 mL/min calculated by receiver-operator characteristics curves. Moreover, multivariate logistic regression analysis revealed that non-administration of zoledronic acid (odds ratio 10.43,
p<0.05) and CCr less than 50.0 mL/min (odds ratio 5.90,
p<0.05) were independent risk factors for denosumab-induced hypocalcemia. These findings provide useful information regarding the monitoring of hypocalcemia in patients receiving denosumab.
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Xianqin Wang, Xiaole Chen, Mengchun Chen, Guoxin Hu, Jianshe Ma, Jianc ...
2013 Volume 36 Issue 10 Pages
1627-1633
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
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Hydrogen sulfide (H
2S) is one of the neurotoxic gases with suffocating and irritating. Its main target organs of toxic effects are the central nervous system and respiratory system. Cocktail method was used to evaluate the influence of chronic hydrogen sulfide poisoning on the activities of cytochrome P450 (CYP450) isoforms CYP1A2, CYP2C9, CYP2B6 and CYP2D6, which were reflected by the changes of pharmacokinetic parameters of 4 specific probe drugs phenacetin, tolbutamide bupropion and metroprolol, respectively. The experimental rats were randomly divided into two groups, control group and chronic hydrogen sulfide poisoning group. The chronic hydrogen sulfide poisoning group rats were inhaled 20 ppm for 1 h twice a day for 40 d. The mixture of 4 probes was given to rats through sublingual veins and the blood samples were obtained at a series of time-points through the caudal vein. The concentrations of probe drugs in rat plasma were measured by liquid chromatography-mass spectrometry (LC-MS). In the experiment for chronic hydrogen sulfide poisoning and control group, there was a statistically significant difference in the area under the plasma concentration–time curve from zero to infinity (
AUC0–∞), plasma clearance (
CL) and maximum plasma concentration (
Cmax) for phenacetin and bupropion, while there was no statistical pharmacokinetics difference for tolbutamide and metoprolol. Chronic hydrogen sulfide poisoning could induce the activity of CYP1A2 and CYP2B6 of rats.
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Shanjun Tan, Feng Zhou, Ning Li, Qiantong Dong, Xiaodong Zhang, Xingzh ...
2013 Volume 36 Issue 10 Pages
1634-1639
Published: October 01, 2013
Released on J-STAGE: October 01, 2013
Advance online publication: August 06, 2013
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Ginsenoside Rb1 (GRb1), one of the principle active ingredients of
Panax ginseng, exerts multiple pharmacological activities to fight fatigue. In the present study, we investigate the anti-fatigue effect of GRb1 on postoperative fatigue syndrome (POFS) in a rat model induced by major small intestinal resection. GRb1 (10 mg/kg) was administrated intraperitoneally once daily for 1, 3, 7, and 10 d from the operation day. Anti-fatigue effect was assessed by grasping test and biochemical parameters in blood or skeletal muscle were determined by autoanalyzer or commercially available kits. Transmission electron microscope was applied to observe the ultra microstructure of skeletal muscles. The results revealed that GRb1 significantly enhanced rat maximum grip strength with POFS. Similarly, negative alterations in biochemical parameters (lactic acid, hepatic glycogen, muscle glycogen and malondialdehyde) of POFS rats were improved by GRb1. In addition, GRb1 also increased the activity of lactate dehydrogenase and superoxide dismutase in POFS. No significant differences of levels of blood urea nitrogen and ultra microstructure of skeletal muscles were found between the POFS and GRb1 treatment rats. The potent anti-fatigue effect of GRb1 on POFS might be achieved through improvement of energy metabolism and suppression of skeletal muscle oxidative stress.
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