ORALS

SESSION: OxidativeThuAM-R5	Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings
Thu Oct, 24 2019 / Room: Zeus (55/Mezz. F)
Session Chairs: Christian Amatore; HARUHIKO INUFUSA; Session Monitor: TBA

11:20: [OxidativeThuAM01]
The Effect of Ginseng on Human Antioxidant Capacity
Hiroshi Ichikawa¹ ; Yuta Noguchi² ; Maryam Shafei² ; Chiharu Myo² ; Keiko Kobayashi³ ; Yukiko Minamiyama⁴ ; Haruhiko .inufusa⁵ ; Toshikazu Yoshikawa⁶ ; ¹Doshisha University, Kyotanabe City, Japan; ²Major of Medical Life Systems, Graduate School of Life and Medical Sciences, Doshisha University, Kyotanabe City, Japan; ³Kyoto Prefectural University, Kyoto, Japan; ⁴Kyoto Prefectural University, KYoto, Japan; ⁵CEO, TIMA/Gifu University, Osaka, Japan; ⁶Louis Pasteur Center for Med. Res., Tohoku, Japan;
Paper Id: 219 [Abstract]

Ginseng has been reported about for its immunostimulation and its effects on various diseases such as obesity, diabetes and cancer. In this study, from the viewpoint of antioxidant and oxidative stress, the influence of ginseng on humans was examined. By using the MULTIple free-radical Scavenging (MULTIS method), we measured the scavenging activity of the reactive oxygen species: hydroxyl radical (・OH), superoxide radical (O₂^・-), alkyloxy radical (RO・), alkyl peroxy radical (ROO・), methyl radical (・CH₃), and singlet oxygen (¹O₂). We also evaluated the antioxidant capacity multifaceted. On the first day, subjects’ samples (plasma and saliva) were taken before ingesting ginseng tablets (n=5). After that, the samples were taken again, 4 hours after the administration of 18 tablets. They continued taking 18 tablets per day from the second day to the sixth day. On the seventh day, the samples were collected. The antioxidant capacity of the samples was examined using the MULTIS method. By ingestion of ginseng tablets, the ・OH scavenging activity of samples increased after 1 week. Also, plasma ・CH₃, and saliva O₂^・- scavenging activity increased. It was suggested that ginseng improved the antioxidant capacity of human.

References:
1. Chasing great paths of Helmut Sies "Oxidative Stress".
Majima HJ, Indo HP, Nakanishi I, Suenaga S, Matsumoto K, Matsui H, Minamiyama Y, Ichikawa H, Yen HC, Hawkins CL, Davies MJ, Ozawa T, St Clair DK
Archives of biochemistry and biophysics 595 54-60 2016
2. A mitochondrial superoxide theory for oxidative stress diseases and aging
Indo Hiroko P., Yen Hsiu-Chuan, Nakanishi Ikuo, Matsumoto Ken-ichiro, Tamura Masato, Nagano Yumiko, Matsui Hirofumi, Gusev Oleg, Cornette Richard, Okuda Takashi, Minamiyama Yukiko, Ichikawa Hiroshi, Suenaga Shigeaki, Oki Misato, Sato Tsuyoshi, Ozawa Toshihiko, St Clair Daret K., Majima Hideyuki J.
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION 56(1) 1-7 2015

SESSION: OxidativeThuAM-R5	Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings
Thu Oct, 24 2019 / Room: Zeus (55/Mezz. F)
Session Chairs: Christian Amatore; HARUHIKO INUFUSA; Session Monitor: TBA

11:45: [OxidativeThuAM02]
Exposome-Induced Oxidative Stress and Protective Effects of Antioxidants in Rats
Yukiko Minamiyama¹ ; Keiko Kobayashi² ; Ririko Kawatani³ ; Hiroshi Ichikawa⁴ ; Shigekazu Takemura⁵ ; Fuhua (fukka) Yang (you)⁶ ; Haruhiko Inufusa⁷ ; Toshikazu Yoshikawa⁸ ; ¹Kyoto Prefectural University, KYoto, Japan; ²Kyoto Prefectural University, Kyoto, Japan; ³Graduate School of Life and Medical Sciences Doshisha University, Kyotanabe, Japan; ⁴Doshisha University, Kyotanabe City, Japan; ⁵Graduate School of Medicine, Osaka City University, Osaka, Japan; ⁶Gifu University Division of Anaerobe Research, Gifu, Japan; ⁷TIMA Japan Corporation, Gifu, Japan; ⁸Louis Pasteur Center for Med. Res., Tohoku, Japan;
Paper Id: 196 [Abstract]

The exposome can be defined as the totality of exposures (diet, lifestyle, occupational, and environmental factors) received by an individual throughout the entire lifetime. It is unclear how these exposures are related to health. There is an increasing trend to intake food additives due to food mileage extension and maintenance of a healthy lifestyle. Therefore, we investigated the effect of aspartame (APM), an artificial sweetener, and ortho-phenyl phenol (OPP), a broad-spectrum fungicide and antibacterial agent, on oxidative stress in rats. APM (250 mg/kg/day; 1/16 NOAEL) or OPP (1 &#u181;g/kg/day; 1/10⁵ NOAEL) were administered to rats for &#~8776;eight weeks, through their mixed diet and drinking water, respectively. Administration of both exposomes for two weeks led to a significant reduction in reactive oxygen specie (ROS)-scavenging ability for hydroxyl radicals in plasma. In epididymis and hippocampus, both exposome treatments increased the 4-hydroxy-2-nonenal (HNE) levels, an index of lipid peroxidation. APM treatment for two weeks increased ROS generation in sperms without motility changes. Moreover, APM treatment for eight weeks slightly decreased sperm motility. Furthermore, amyloid beta (Abeta) levels were significantly increased in both epididymis and hippocampus after two weeks of OPP administration, that may be related to male infertility and dementia. Pretreatment with the antioxidant Twendee X (20 mg/kg/day; TIMA Japan) inhibited the Abeta level increase in both tissues. In conclusion, our data indicate that some exposomes systemically induce oxidative stress and increase Abeta levels in both epididymis and hippocampus. These results suggested that effective antioxidants such as Twendee X can inhibit exposome-induced oxidative stress in male infertility and neurodegenerative diseases.

References:
1. Takemura S, Ichikawa H, Naito Y, Takagi T, Yoshikawa T, Minamiyama Y. S-allyl cysteine ameliorates the quality of sperm and provides protection from age-related sperm dysfunction and oxidative stress in rats.\nJ Clin Biochem Nutr. 2014 Nov;55(3):155-61.\n2. Minamiyama Y, Ichikawa H, Takemura S, Kusunoki H, Naito Y, Yoshikawa T. Generation of reactive oxygen species in sperms of rats as an earlier marker for evaluating the toxicity of endocrine-disrupting chemicals.\nFree Radic Res. 2010 Dec;44(12):1398-406.

SESSION: OxidativeThuPM1-R5	Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings
Thu Oct, 24 2019 / Room: Zeus (55/Mezz. F)
Session Chairs: Toshikazu Yoshikawa; Shigeru Hirano; Session Monitor: TBA

14:00: [OxidativeThuPM105]
Oxidative Stress Disease (Free Radical Disease) and its Prevention - Appearance of the Effective Antioxidant Material
Toshikazu Yoshikawa¹ ; ¹Louis Pasteur Center for Med. Res., Tohoku, Japan;
Paper Id: 478 [Abstract]

It is widely known that oxidative stress causes many diseases. Free radical species triggering these results from transition metals, ischemia/reperfusion, drugs, inflammation, and environmental factors such as iron, and it causes the pathologies. Materials and mechanisms that are essential to the survival of many organisms including cells, protein and DNA is ruined by a free radical, causing many diseases, and these diseases were proposed that we called these oxidation stress diseases (free radical diseases) as a general term. A lot of specialized international journals about these are proud of the impact factor which is high in each. Although the disorder developmental mechanics and protective efficacy are studied in vitro and in animal experiments in detail, there is yet few antioxidative prevention or drugs to treat for those diseases in clinical studies using human. Drug RADICUT (cut a free radical according to the name. Generic name “Edaravone”) used for brain stroke treatment widely or vitamin E effective in non-alcoholic lipid hepatitis (NASH) are the representative examples. These and other antioxidants cannot be an effective means for treatment and prevention of many other oxidative stress diseases probably because of the characteristics of the drugs. Appearance of a versatile antioxidant material which expresses an effect of prevention and treatment for many oxidation stress diseases without showing any side effects has been waited for. A supplement named Twendee X which was the vitamins and amino acids complex showing strong antioxidant effect finally came up recently. Ingredients and composition ratio of Twendee X was developed to maximize its antioxidant effects. The randomized, double-blind placebo control study of dementia prevention using Twendee X for human with mild cognitive impairment (MCI) was conducted by Professor Koji Abe of the Okayama University, Department of Neurology. Surprisingly, the result showed its preventive effect of MCI progression with a significant difference [1], and, as for this antioxidant material, it has been suggested to be effective in the prevention and treatment of many oxidative stress diseases, and more results are expected in the future. Here, based on these results, I will discuss about possibility of prevention and treatment by antioxidant materials.

References:
[1] J Alzheimers Dis. 2019 Aug 24. doi: 10.3233/JAD-190644

SESSION: OxidativeThuPM1-R5	Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings
Thu Oct, 24 2019 / Room: Zeus (55/Mezz. F)
Session Chairs: Toshikazu Yoshikawa; Shigeru Hirano; Session Monitor: TBA

14:25: [OxidativeThuPM106]
Role of Anti-oxidant Twendee X for Maintenance of Voice and Swallow
Shigeru Hirano¹ ; Haruhiko Inufusa² ; Toshikazu Yoshikawa³ ; ¹Kyoto Prefectural University of Medicine, Kyoto, Japan; ²TIMA Japan Corporation, Gifu, Japan; ³Louis Pasteur Center for Med. Res., Tohoku, Japan;
Paper Id: 266 [Abstract]

The larynx and pharynx have important roles in maintaining voice and swallowing functions. Age-related deterioration of vocal and swallowing functions has become a significant problem for the elderly which can lead to aspiration pneumonia in the worst cases. Age-related histological and functional deficit of the pharyngolaryngeal system is the main issue. The vocal fold, the producer of the voice, becomes atrophied and weak which causes glottic insufficiency with reduced mucosal vibration. The voice becomes harsh and weak. Glottic insufficiency also causes mis-swallowing. Laryngeal elevation and pharyngeal constriction are weakened with age which can lead to aspiration. We have confirmed that oxidative stress increases with age in the vocal fold mucosa and muscle, as well as the pharyngeal muscles. Reactive oxygen species (ROS) damage the tissue and hamper function. In the case of singers or other professional voice users, overuse of the vocal fold also causes damage to the function of the vocal fold via ROS. Anti-oxidants are the promising material that can maintain or improve the voice and the swallowing ability. We have revealed that anti-oxidants can maintain the vocal fold during excessive vocal loading tasks, avoiding inflammation or exhaustion of the vocal fold. Twendee X (TWX) has proven the strongest anti-oxidant, and our preliminary study demonstrated that an opera singer's voice was well maintained with the 1-month use of TWX. Another aspect of TWX is its capability to reduce allergic inflammation in the upper airway which is also important for protection of the pharyngolarynx. Anti-oxidants should be effective, useful, and promising for maintaining the pharyngolarynx which secures voicing and swallowing functions.

References:
[1]Inufusa H. Characterization of cell protection effects of Twendee X by oxidative stress. J World Mitochondria Soc 2016;2:42.
[2]Kaneko M, Kishimoto Y, Suzuki R, et al. Protective Effect of Astaxanthin on Vocal Fold Injury and Inflammation Due to Vocal Loading: A Clinical Trial. J Voice. 2017;31(3):352-358.

SESSION: OxidativeThuPM1-R5	Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings
Thu Oct, 24 2019 / Room: Zeus (55/Mezz. F)
Session Chairs: Toshikazu Yoshikawa; Shigeru Hirano; Session Monitor: TBA

15:15: [OxidativeThuPM108]
Brain Disease and Oxidative Stress: Ischemia and Dementia
Haruhiko Inufusa¹ ; Koji Abe² ; Isao Tadokoro² ; Fuhua (fukka) Yang (you)³ ; Toshikazu Yoshikawa⁴ ; ¹TIMA Japan Corporation, Gifu, Japan; ²Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; ³Gifu University Division of Anaerobe Research, Gifu, Japan; ⁴Louis Pasteur Center for Med. Res., Tohoku, Japan;
Paper Id: 229 [Abstract]

Reactive Oxygen Species (ROS) are closely related to various diseases of the brain. Twendee X (TWX) is an antioxidant composition consisting of Vitamin C, L-Glutamine, L-Cystine or L-Cysteine, Riboflavin, Succinic acid, Fumaric acid, Coenzyme Q10, and Niacin. TWX was invented from the basic experiments of alcohol, glucose, and fat metabolisms (1-4). TWX strongly reduces ROS (Patent: WIPO WO2013/072441 A1, COMPOSITION FOR PROTECTION AGAINST CELL-DAMAGING EFFECTS). Lysozyme radiation experiments showed that the antioxidant effects of TWX are 6-7 times higher than Vitamin C (Data from Dr. Helmut Durschschlarg, Regensburg Univ. Germany). Oxidative stress and mitochondrial expert ICDD (France) experiments using hepatic cancer cell line HepG2 showed TWX decrease of 63% of mitochondrial ROS and an increase of 147% mitochondrial SOD. ICDD confirmed that TWX is safe and has most strong anti-ROS and protection effects from ROS. TWX increase Neogenesis nerves cell numbers of the hippocampal dentate gyrus of the 56 weeks mouse. The same occurs within 6 weeks by TWX administration. The mitochondrial metabolism of the mouse’s hippocampal dentate gyrus was activated by TWX administration by the metabolome analysis. The model of the brain of the mouse for ischemia and Alzheimer's disease were used to evaluate the effects of TWX. The double blind clinical trial of the Japanese Association for Prevention of Dementia from autumn 2017 to March 2019 for mild cognitive impairment was performed to analyze TWX prevention effects on Alzheimer's disease. TWX decreased volume of brain ischemia to 2/3, and inflammation and oxidative stress in the brain was also reduced in the mouse ischemia model. TWX inhibited deposition of amyloid beta. Inflammation and oxidative stress in the brain was also reduced in the mouse model of Alzheimer. Double blind clinical research resulted in the TWX group significantly increasing the score of the Mini Mental State Examination compared to the placebo group at 6 months after the start of TWX administration. Thus, TWX is effective to prevent Alzheimer's disease and vascular dementia.

References:
1. Novel compositions and uses thereof WO 2008071790 A3\n2. Antioxidant composition and its use in diabetes EP 1932542 A1\n3. Pretreatment Twendee X reduced acute ischemic brain damage. Kusaki M, Inufusa H, Abe K, JSCVD 2017; 26: 1191-1196\n4. Clinical and Pathological Benefit of Twendee X in Alzheimer's Disease Transgenic Mice with Chronic Cerebral Hypoperfusion. XiaLiu, Abe K https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.03.029