著者

Shinichi Goto Takayuki Morikawa Akiko Kubo Keiyo Takubo Keiichi Fukuda Mayumi Kajimura Makoto Suematsu

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

vol.63, no.1, pp.70-79, 2018 (Released:2018-07-01)

参考文献数

30

被引用文献数

6

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Carbon monoxide-generating heme oxygenase-2 is expressed in neurons and plays a crucial role for regulating hypoxic vasodilation through mechanisms unlocking carbon monoxide-dependent inhibition of H2S-generating cystathionine β-synthase expressed in astrocytes. This study aims to examine whether heme oxygenase-2 plays a protective role in mice against stroke. Focal ischemia was induced by middle cerebral artery occlusion. Regional differences in metabolites among ipsilateral and contralateral hemispheres were analysed by quantitative imaging mass spectrometry equipped with an image-processing platform to optimize comparison of local metabolite contents among different animals. Under normoxia, blood flow velocity in precapillary arterioles were significantly elevated in heme oxygenase-2-null mice vs controls, while metabolic intermediates of central carbon metabolism and glutamate synthesis were elevated in the brain of heme oxygenase-2-null mice, suggesting greater metabolic demands to induce hyperemia in these mice. In response to focal ischemia, heme oxygenase-2-null mice exhibited greater regions of ischemic core that coincide with notable decreases in energy metabolism in the contralateral hemisphere as well as in penumbra. In conclusion, these findings suggest that heme oxygenase-2 is involved in mechanisms by which not only protects against compromised energy metabolism of the ipsilateral hemisphere but also ameliorates transhemispheric diaschisis of the contralateral hemisphere in ischemic brain.

著者

Yoshichika Kawai Erika Nuka

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

vol.62, no.1, pp.3-10, 2018 (Released:2018-01-01)

参考文献数

74

被引用文献数

12

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Reactive oxygen species and their reaction products can damage DNA to form mutagenic lesions. Among the reactive species, lipid peroxidation-derived aldehydes react with nucleobases and form bulky exocyclic adducts. Many types of aldehyde-derived DNA adducts have been characterized, identified and detected in vitro and in vivo, whereas relative quantitative and pathophysiological contributions of each adduct still remain unclear. In recent years, an abundant class of DNA adducts derived from 4-oxo-2-alkenals have been identified, in addition to classic aldehyde-derived adducts. The presence of 4-oxo-2-alkenal-derived DNA adducts associated with age-related diseases has been revealed in rodents and humans. In vitro studies have demonstrated that 4-oxo-2-alkenals, as compared with other classes of lipid peroxidation-derived aldehydes, are highly reactive with nucleobases. It has been generally recognized that 4-oxo-2-alkenals are generated through oxidative degradation of the corresponding 4-hydroperoxy-2-alkenals, homolytic degradation products of polyunsaturated fatty acid hydroperoxides. Our recent results have also shown an alternative pathway for the formation of 4-oxo-2-alkenals, in which 2-alkenals could undergo the metal-catalyzed autoxidation resulting in the formation of the corresponding 4-oxo-2-alkenals. This review summarizes the basis of the formation of lipid peroxidation-derived genotoxic aldehydes and their covalent adduction to nucleobases, especially focusing on the abundance of 4-oxo-2-alkenal-derived DNA adducts.

著者

Ayumi Yoshimoto Takashi Uebanso Mutsumi Nakahashi Takaaki Shimohata Kazuaki Mawatari Akira Takahashi

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

vol.62, no.2, pp.155-160, 2018 (Released:2018-03-01)

参考文献数

25

被引用文献数

12

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Several environmental factors during the prenatal period transgenerationally affect the health of newborns in later life. Because low-dose antibiotics have been used for promoting the growth of crops and livestock in agriculture, humans may have ingested residual antibiotics for several decades. However, the effect of prenatal administration of low-dose antibiotics on newborns’ health in later life is unclear. In the present study, we found that prenatal treatment of murine mothers with low-dose antibiotics increased the abundance of bacteria of the phylum Firmicutes and the genera Clostridium IV and XIVa in feces from pups. In addition, the body fat percentage of mice in the antibiotic-treated group was higher than those in the control group at 12 weeks of age even though all pups were fed a standard diet. The body fat percentage of all mice was correlated with the abundance of fecal bacteria of Clostridium IV and XIVa. These results predict that low-dose antibiotic administration during the prenatal period affects the gut microbiota of newborns and possibly their health in later life.

著者

Izumi Tsukayama Keisuke Toda Yasunori Takeda Takuto Mega Mitsuki Tanaka Yuki Kawakami Yoshitaka Takahashi Masumi Kimoto Kei Yamamoto Yoshimi Miki Makoto Murakami Toshiko Suzuki-Yamamoto

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

vol.62, no.2, pp.139-147, 2018 (Released:2018-03-01)

参考文献数

41

被引用文献数

7

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Hyperproduced prostaglandin E2 by cyclooxygenase-2 and microsomal prostaglandin E synthase-1 evokes several pathophysiological responses such as inflammation and carcinogenesis. Our recent study demonstrated that Dioscorea japonica extract suppressed the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 and induced apoptosis in lung carcinoma A549 cells. In the present study, we investigated the effects of Dioscorea japonica on squamous cell carcinoma of mouse skin. Dioscorea japonica feeding and Dioscorea japonica extract topical application suppressed the expression of cyclooxygenase-2, microsomal prostaglandin E synthase-1, interleukin-1β and interleukin-6 and inhibited tumor formation, hyperplasia and inflammatory cell infiltration. Immunohistochemical analyses showed the immunoreactivities of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in tumor keratinocytes and stronger immunoreactivities of cyclooxygenase-2 and hematopoietic prostaglandin D synthase in epidermal dendritic cells (Langerhans cells). Treatment with Dioscorea japonica decreased the immunoreactivity of cyclooxygenase-2 and microsomal prostaglandin E synthase-1. These results indicate that Dioscorea japonica may have inhibitory effects on inflammation and carcinogenesis via suppression of the prostaglandin E2 synthetic pathway.

著者

Suk Pyo Shin Yoon Mi Choi Won Hee Kim Sung Pyo Hong Jong-Min Park Joohee Kim Oran Kwon Eun Hyun Lee Ki Baik Hahm

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

vol.62, no.2, pp.179-186, 2018 (Released:2018-03-01)

参考文献数

41

被引用文献数

37

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The exact pathogenesis of diarrhea-dominant irritable bowel syndrome (IBS) is not known, but the abnormal microbiota of the gastrointestinal tract is considered to be one of the important contributing factors as in other gastrointestinal diseases such as inflammatory bowel disease, antibiotic-associated diarrhea, and colorectal cancer as well as systemic diseases. Though diverse trials of probiotics had been continued in the treatment of diarrhea-IBS, only a few proved by randomized clinical trial. To prove the efficacy of Lactobacillus gasseri BNR17 isolated from breast milk in patients with diarrhea-IBS, prospective, randomized, placebo controlled clinical trial was done including health related-quality of life analysis, colon transit time, and the changes of fecal microbiota. BNR17 significantly improved the symptoms of diarrhea compared to control group. Health related-QOL analysis showed significant improvement of abdominal pain, distension, disturbed daily life, and mean defecation frequency with BNR17. On comparative CTT before and after BNR17, 6 out of 24 subjects showed significant correction of rapid colon transit pattern, while only 2 out of 24 in placebo (p<0.01). Upon fecal microbiota analysis, BNR17 significantly increased B. fecalis, E. rectale, C. aerofaciens, F. prausnitzil and B. steroris. Conclusively, Lactobacillus gasseri BNR17 can be a potential probiotics to ameliorate diarrhea-IBS.

著者

Tomohisa Takagi Yuji Naito Ryo Inoue Saori Kashiwagi Kazuhiko Uchiyama Katsura Mizushima Saeko Tsuchiya Tetsuya Okayama Osamu Dohi Naohisa Yoshida Kazuhiro Kamada Takeshi Ishikawa Osamu Handa Hideyuki Konishi Kayo Okuda Yoshimasa Tsujimoto Hiromu Ohnogi Yoshito Itoh

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

pp.17-78, (Released:2017-12-12)

参考文献数

23

被引用文献数

86

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Proton pump inhibitors (PPIs) are widely used to treat gastro-esophageal reflux and prevent gastric ulcers, and have been considered as low risk. However, recent studies have identified possible associations between PPI use and gut microbiota, suggesting that PPIs use increases the risk of enteric infections, including Clostridium difficile infection. To investigate gut microbiota in Japanese PPIs users, we conducted 16S metagenomics analysis of fecal samples collected from PPI users and healthy adults. In total, 36 PPI users and 36 PPI non-users (as control subjects) matched by age and sex were recruited and fecal samples were obtained to analyze the gut microbiome using 16S rRNA gene sequencing. There were significant differences in the microbial structure between PPI non-users and PPI users. In contrast, the analysis of α-diversity revealed no significant differences between PPI non-users and PPI users. When comparing in genus level between these two groups, the genera Streptococcus was significantly abundant and the genera Faecalibacterium was significantly decreased in PPI users. Our findings indicate a probable association between PPI use and the alternation of microbiota. These alterations might provide a mechanism by which PPIs predispose enteric infection such as Clostridium difficile infection.

著者

Keiko Unno Shigenori Noda Yohei Kawasaki Hiroshi Yamada Akio Morita Kazuaki Iguchi Yoriyuki Nakamura

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

vol.61, no.3, pp.210-216, 2017 (Released:2017-11-01)

参考文献数

51

被引用文献数

26

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Epidemiological and animal studies have demonstrated that ingestion of green tea enhances healthy life. However, caffeine in green tea can interfere with sleep. In this report, we examined the effect of green tea with lowered caffeine, low-caffeine green tea, on stress and sleep of the elderly. The participants (n = 10, mean age 89.3 ± 4.2 years) drank five cups/day of standard green tea for 1 week. Subsequently, they drank five cups/day of low-caffeine green tea for 2 weeks. Salivary α-amylase activity (sAA) was measured as a stress marker. Sleep stages were measured using a portable electroencephalography (n = 7, 6 female and 1 male). The level of sAA in the morning (sAAm) was significantly lower when the participants drank low-caffeine green tea than standard green tea. While the levels of sAAm were different among individuals, lower sAAm correlated with a higher quality of sleep. In those participants whose sAAm was lowered by the ingestion of low-caffeine green tea, some sleep parameters improved. Daily ingestion of low-caffeine green tea may be a beneficial tool for improving the quality of sleep of the elderly via the suppression of stress, although further research is required to fortify this hypothesis.

著者

Huanhuan Liu Huijia Zhong Liang Leng Zhuoqin Jiang

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

pp.16-98, (Released:2017-07-20)

参考文献数

35

被引用文献数

12 31

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Soy isoflavone has benefits for metabolic syndrome but the mechanism is not completely understood. This study was designed to determine the effects of soy isoflavone on hepatic fat accumulation in non-alcoholic fatty liver disease (NAFLD) rats induced by high fat diet (HFD). Sprague-Dawley rats were administrated with a normal fat diet (control), HFD (NAFLD model), HFD with 10 or 20 mg/kg soy isoflavone daily for 12 weeks. Hepatic and serum lipid contents, liver histopathological examination, serum alanine transaminase (ALT), protein and mRNA expression of sterol regulatory element binding protein (SREBP)-1c, fatty acid synthase (FAS), peroxisome proliferator-activated receptor (PPAR) α were assayed respectively. Our study found that soy isoflavone reduced HFD-induced lipid accumulation in liver, serum ALT and improved liver lobule structure. In addition, the expression of SREBP-1c and FAS was lower, whereas protein level of PPARα was higher in two soy isoflavone groups than that of the HFD group. Collectively, these results demonstrate that soy isoflavone is capable of alleviating hepatic steatosis and delaying the progression of NAFLD via inhibiting lipogenesis and promoting fatty acid oxidation in liver.

著者

Hisao EKIMOTO Kimihiko TAKADA Takao OHNUKI Katsutoshi TAKAHASHI Akira MATSUDA Tomohisa TAKITA Hamao UMEZAWA

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

vol.2, no.1, pp.25-31, 1987 (Released:2010-02-25)

参考文献数

26

被引用文献数

7 11

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Sensitivity to bleomycin-induced pulmonary fibrosis was tested in various strains of mice. Among the strains examined, ICR, C57BL/10(H-2b), and C3H/He(H-2k) mice were highly sensitive to the induced pulmonary fibrosis; C57BL/6(H-2b), DBA/2(H-2d), A/J(H-2a), B6C3F1 and BDF1 mice were moderately sensitive, and CBA/JN(H-2k), BALB/c(H-2d), CDF1 and CBF1 mice were less sensitive. In congenic mice, which differ from each other only in the H-2 locus, C57BL/10(H-2b) was highly sensitive; B10·D2(H-2d) was moderately sensitive; and B10·BR(H-2k) and B10·A(H-2a) were less sensitive. Thus, the sensitivity differed depending on the haplotype of the H-2 genes. Furthermore, non-H-2 genes also seemed to be involved in the sensitivity to the pulmonary fibrosis. There was no correlation between the sensitivity to pulmonary fibrosis and enzyme activities such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the lung tissues, but the levels of reducing agents such as ascorbic acid and tocopherol in the lungs were inversely correlated with the sensitivity to the pulmonary fibrosis, except in the case of BALB/c and its F1 mice.

著者

Ryo Koufuchi Takahashi Ayako Tamaki Yoh Ohnishi-Kameyama Mayumi Inoue Hiroko Saito Ichiro

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

vol.55, no.3, pp.168-173, 2014

被引用文献数

14

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Dry mouth, which is characterized by decreased salivation, has a number of causes; the involvement of estrogen has been suggested as symptoms typically develop in middle-aged females. However, there is a lack of consensus regarding the treatment of this condition. Soy isoflavones, a subgroup of flavonoids, are abundantly found in the soy germ. They are thought to exert a number of effects by specifically binding to estrogen receptors due to their structural similarity to estrogen. Recently, soy isoflavones have been found to exert antioxidant effects, ameliorating disorders caused by reactive oxygen/free radicals. Based on these observations, the effects of soybean isoflavones on impaired salivary secretion were studied in patients with dry mouth. Soy isoflavone aglycones were administered at 25 mg per day to 15 subjects with an average age of 67.9 ± 8.0 years for 2 months, and salivary secretion was analyzed. The results showed a significant improvement based on the saliva flow rate and self-completed questionnaire, thus suggesting the usefulness of isoflavones in improving the symptoms of salivary gland hypofunction.

著者

Tamura Masato Matsui Hirofumi Kaneko Tsuyoshi Hyodo Ichinosuke

出版者

Society for Free Radical Research Japan

雑誌

Journal of clinical biochemistry and nutrition (ISSN:09120009)

巻号頁・発行日

vol.53, no.2, pp.75-80, 2013-08

被引用文献数

45 4

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Alcohol/ethanol has been reported to derived necrosis and apoptosis with an oxidative stress in gastric mucosal cells. However the clear evidence for reactive oxygen species (ROS) generation by alcohol in gastric cells in vitro is none. In this study, we elucidated ethanol is an oxidative stress inducer on rat gastric epithelial cells by electron paramagnetic resonance measurement in living cells. We also confirmed whether ethanol-induced cellular ROS was derived from mitochondria or not. The results of cellular ROS determination showed that an increment of cellular ROS was shown for 15 min from exposing 1% (v/v) ethanol. Lipid peroxidation in cellular membrane also induced by 1% ethanol and the tendency is same in the results of cellular ROS determination. JC-1 stained showed the decrement of mitochondrial membrane potential. Additionally the localization of cellular ROS coincided with mitochondria. These results indicated that ethanol is not merely a necrotizing factor for gastric epithelial cells, but also an oxidative stress inducer via injured mitochondria.

著者

Masaru Ohtani Shigeo Kawada Taizo Seki Yasuyuki Okamoto

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

vol.50, no.2, pp.162-168, 2012 (Released:2012-02-28)

参考文献数

46

被引用文献数

6 8

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The purpose of this study was to investigate the effects of supplementation with amino acids and vitamins on health conditions in unhealthy older people. One bedridden inpatient group (n = 10; mean age, 79.8 ± 8.5 y) and one outpatient group (n = 9; mean age, 72.9 ± 12.2 y) participated in this study. A mixture supplementation with amino acids containing arginine (500 mg/day), glutamine (600 mg/day), and leucine (1200 mg/day), and 11 kinds of vitamins was daily administrated for 8 weeks. In both groups, general blood biomarkers such as white blood cell count, natural killer cell activity, and C-reactive protein levels were measured. All measurements were taken before (baseline), at 4 weeks (mid-point), and after each trial (post-point). At mid-point, natural killer cell activity in the outpatient group increased significantly compared to baseline. At post-point, natural killer cell activity in the outpatient and inpatient groups increased significantly compared to baseline. The other blood biomarkers did not show any significant change throughout the trial. This pilot study suggested that a mixture of arginine, glutamine, leucine, and vitamins is useful to support innate immunity in unhealthy older people, even if their diseases, symptoms, and prescribed medicines are different.

著者

Soo-Heon Park Chul-Soo Cho Oh-Young Lee Jae-Bum Jun San-Ren Lin Li-Ya Zhou Yao-Zong Yuan Zhao-Shen Li Xiao-Hua Hou Hong-Chuan Zhao Udom Kachintorn Chomsri Kositchaiwat Comson Lertkupinit

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

vol.40, no.2, pp.148-155, 2007 (Released:2007-03-14)

参考文献数

15

被引用文献数

57 65

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Nonsteroidal anti-inflammatory drugs (NSAIDs) have gastrointestinal side effects such as dyspepsia, peptic ulcer, hemorrhage, and perforation. Misoprostol and PPIs have been used to prevent NSAID-induced gastroduodenal injury. Rebamipide increases gastric mucus and stimulates the production of endogenous prostaglandins. The prophylactic effect of rebamipide on NSAID-induced gastrointestinal complications is unknown. The aim of this study was to compare NSAID-induced gastrointestinal complications in rebamipide- and misoprostol-treated groups. Patients were randomized to two groups and took a conventional NSAID plus rebamipide or misoprostol for 12 weeks. Gastric mucosal damage was evaluated by endoscopy at screening and the end of the study. The prevalences of active gastric ulcer were 7/176 (3.9%) in the rebamipide group and 3/156 (1.9%) in the misoprostol group. The prevalences of peptic ulcer were 8/176 (4.5%) in the rebamipide group and 7/156 (4.4%) in the misoprostol group. The cumulative incidences of peptic ulcer in the high-risk subgroup were 6/151 (4.0%) for rebamipide and 6/154 (3.9%) for misoprostol. In conclusion, rebamipide prevented NSAID-induced peptic ulcer as effectively as misoprostol in patients on long-term NSAID therapy. Rebamipide may be a useful therapeutic option for the prevention of NSAID-induced gastrointestinal ulcer because of its therapeutic effect and safety.