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Protective effects of oral glutathione on fasting-induced intestinal atrophy through oxidative stress

World Journal of Gastroenterology 2017年第36期23卷 6650-6664页

作者： Hiroyuki Uchida yukari nakajima Kazuo Ohtake Junta Ito Masahiko Morita Ayako Kamimura Jun Kobayashi Division of Pathophysiology Department of Clinical Dietetics and Human NutritionFaculty of Pharmaceutical ScienceJosai University Kyowa Hakko Bio Co. Ltd.Healthcare Products Development Center

AIM To determine whether oral glutathione(GSH)administration can alleviate the effects of fasting-induced intestinal atrophy in the small intestinal mucosa. METHODS Rats were divided into eight groups.One group was fed ad libitum,another was fed ad libitum and received oral GSH,and six groups were administrated saline(SA)or GSH orally during fasting.Mucosal height,apoptosis,and cell proliferation in the jejunum were histologically evaluated.i NOS protein expression(by immunohistochemistry),nitrite levels(by high performance liquid chromatography,as a measure of NO production),8-hydroxydeoxyguanosine formation(by ELISA,indicating ROS levels),glutathione/oxidized glutathione(GSH/GSSG)ratio(by enzymatic colorimetric detection),andγ-glutamyl transpeptidase(Ggt1)mR NA levels in the jejunum(by semi-quantitative RT-PCR)were also estimated. RESULTS O r a l G S H a d m i n i s t r a t i o n w a s d e m o n s t r a t e d t o drastically reduce fasting-induced intestinal atrophy in the jejunum.In particular,jejunal mucosal height was enhanced in GSH-treated animals compared to SA-treated animals[527.2±6.9 for 50 mg/kg GSH,567.6±5.4 for 500 mg/kg GSH vs 483.1±4.9(μm),P<0.01at 72 h].This effect was consistent with decreasing changes in GSH-treated animals compared to SA-treated animals for iN OS protein staining[0.337±0.016for 50 mg/kg GSH,0.317±0.017 for 500 mg/kg GSH vs 0.430±0.023(area of staining part/area of tissue),P<0.01 at 72 h]and NO[2.99±0.29 for 50 mg/kg GSH,2.88±0.19 for 500 mg/kg GSH vs 5.34±0.35(nmol/g tissue),P<0.01 at 72 h]and ROS[3.92±0.46for 50 mg/kg GSH,4.58±0.29 for 500 mg/kg GSH vs6.42±0.52(8-OHdG pg/μg DNA),P<0.01,P<0.05at 72 h,respectively]levels as apoptosis mediators in the jejunum.Furthermore,oral GSH administration attenuated cell proliferation decreases in the fasting jejunum[182.5±1.9 for 500 mg/kg GSH vs 155.8±3.4(5-Brd U positive cells/10 crypts),P<0.01 at 72h].Notably,both GSH concentration and Ggt1 m RNA expression in the jejunum were also attenuated in rats following oral administration of GS

关键词： Intestinal atrophy Glutathione Apoptosis Cell proliferation Inducible nitric oxide synthase

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Does Obesity without Hyperglycemia Delay Wound Healing in an Obese Mouse Model Induced by a High-Fat Diet?

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Health 2017年第12期9卷 1660-1679页

作者： Tamae Urai yukari nakajima Kanae Mukai Kimi Asano Mayumi Okuwa Junko Sugama Toshio Nakatani Advanced Health Care Science Research Unit Innovative Integrated Bio-Research Core Institute for Frontier Science Initiative Kanazawa University Ishikawa Japan Department of Clinical Nursing Graduate Course of Nursing Science Division of Health Sciences Graduate School of Medical Sciences Kanazawa University Ishikawa Japan Faculty of Health Sciences Institute of Medical Pharmaceutical and Health Sciences Kanazawa University Ishikawa Japan

It was unclear that wound healing was delayed in obesity without hyperglycemia. The purpose of this study was to compare the wound healing process between obese and non-obese mice without hyperglycemia by attaching a splint. Three-week-old male mice (C57BL/6N) were fed high-fat diets (60% of calories from fat) in the obesity group, and commercial diets in the control group for 15 weeks. Two circular (4 mm in diameter) full-thickness wounds were made on the dorsal skin. Body weights and serum leptin levels were significantly higher in the obesity group than in the control group until day 15 after wounding. Fasting blood glucose levels before wounding were lower in the obesity group than in a hyperglycemic rodent model. The macrophage infiltration into subcutaneous fat before wounding in the obesity group was negligible. The ratios of the wound area were not significantly different between the two groups. No significant differences were observed in the number of neutrophils or macrophages or new blood vessels and ratio of myofibroblasts or collagen fibers between the two groups. Our results demonstrated that cutaneous wound healing was not delayed in the obesity group without hyperglycemia and macrophage infiltration into the subcutaneous fat and with high serum leptin levels.

关键词： Obesity Mouse Cutaneous Wound Healing Splint Inflammation

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The Relationship between Cutaneous Wounds Made on Obese Mice or Those with Decreased Body Weight and Serum Leptin Level

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Health 2016年第11期8卷 1015-1028页

作者： Tamae Urai Haryanto Kanae Mukai Tatsuhiko Matsushita Kimi Asano yukari nakajima Mayumi Okuwa Junko Sugama Toshio Nakatani Department of Clinical Nursing Graduate Course of Nursing Science Division of Health Sciences Graduate School of Medical Sciences Kanazawa University Kanazawa Japan Faculty of Health Sciences Institute of Medical Pharmaceutical and Health Sciences Kanazawa University Kan-azawa Japan Division of Clinical Radiology Service Kyoto University Hospital Kyoto Japan Wellness Promotion Science Center Institute of Medical Pharmaceutical and Health Sciences Kanazawa Uni-versity Kanazawa Japan

Purpose: Not all obese people have hyperglycemia. We wondered about the healing progress in obese people without hyperglycemia. The purpose of this study is to observe the cutaneous wound healing process. Methods: Three-week-old male mice were fed high-fat diets (containing 60% fat) in the diet group, and commercial diets in the control group, ad libitum for 15 weeks. Circle-full-thickness cutaneous wounds were made on the dorsal skin of mice. From day 0 to day 15 after wounding, we analyzed wound healing process. We measured the blood concentration of leptin, and observed the distribution of leptin-positive cells in each wound. Results: Mean body weight, the areas of subcutaneous fat and visceral fat, and the weight of epididymal fat in the diet group were significantly greater than those in the control group at 15 weeks after feeding. The diet group did not feed on the diet after wounding;their body weight decreased remarkably to the level of the control group. The ratio of wound area, re-epithelialization, and collagen fibers did not differ between the diet and control groups on each day. The blood concentration of leptin in the diet group was significantly greater than that in the control group before wounding and until day 6 after wounding (day 0, 10 hour and day 1: p < 0.01, day 6: p < 0.05). Conclusion: The results show that the wound healing process is similar between obese and non-obese mice, and that the decrease in the leptin level in the obese mouse to that in the non-obese mouse may depend on the decrease of body weight of obese mouse.

关键词： Obesity High-Fat Diet Wound Healing Leptin Tension

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Qualitative Comparison between Rats and Humans in Quadrupedal and Bipedal Locomotion

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Journal of Behavioral and Brain Science 2013年第1期3卷 137-149页

作者： Taisei Hosoido Futoshi Mori Keita Kiyoto Takashi Takagi yukari Sano Megumi Goto Katsumi nakajima Naomi Wada Department of Physiology Kinki University School of Medicine Osaka-Sayama Japan Laboratory of Veterinary System Science Yamaguchi University Yamaguchi Japan Osaka Veterinary Referral Center Osaka Japan

Bipedal (Bp) locomotion is one of the most characteristic motor behaviors in human beings. Innate quadrupedal (Qp) four-legged animals also often walk bipedally. The walking posture, however, is significantly different between the two. This suggests that although both have a potential to walk bipedally, however, the human has a body scheme suitable for Bp locomotion, probably its skeletal system. The skeletal system includes the lumbar lordosis, sacral kyphosis, a round pelvis, a large femur neck angle, short feet, and so on. To verify this hypothesis, we compared kinematic and EMG activities between rats and humans during Qp and Bp locomotion on a treadmill belt. The rat is a representative Qp animal, but it is able to acquire Bp walking capability with motor learning. Although the mobile ranges of the hindlimb joint are different during each locomotor pattern between rats and humans, both showed replicable flexion and extension excursion patterns for each joint depending on the locomotor phase. There are many phase-locked EMG bursts between rats and humans during the same walking task and these are observed in the proximal rather than the distal muscles. This suggests that both rats and humans utilize similar neuronal systems for the elaboration of Qp and Bp locomotion. It was interesting that both subjects showed more muscle activities during non-natural locomotor patterns;Qp < Bp for rats and Bp < Qp for humans. This indicates that rat Bp and human Qp walking need more effort and we may be able to find its reason in their skeletal system.

关键词： Human Rat Evolution Posture Locomotion Bipedal Quadrupedal

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