Clinical Pharmacy Research
Clinical Pharmacy Research
JapaneseResearch Content
RESEARCH
The Laboratory of Clinical Pharmacy Research aims to elucidate the onset mechanism of various diseases and the role of reactive oxygen species (ROS) in the manifestation of toxicity of toxic substances, and to develop the results of basic research into the development of new drug treatment methods.
【Research theme】
?Analysis of involvement of oxidized lipid-dependent cell death in the development of various diseases and development of therapeutic methods and biomarkers
?Identification and functional analysis of novel oxidases involved in lipid oxidation
For us, oxygen is an essential substance for producing ATP, which is the most important biological energy for survival. However, in the process, some become highly reactive intermediate metabolites. Since these intermediate metabolites are extremely reactive, they are collectively referred to as "activated oxygen." It is called Reactive Oxygen Species (ROS). ROS refers to superoxide radicals, hydrogen peroxide, hydroxyl radicals and singlet oxygen in a narrow sense, and includes nitric oxide, peroxy radicals, hypochlorous acid, etc. in a broad sense. These ROS In addition to being generated by the decomposition reaction of oxygen molecules by ultraviolet rays, it is also enzymatically produced by oxidases such as lipoxygenase and NADPH oxidase. It is known that the generated ROS oxidatively modifies proteins, lipids, and nucleic acids, which are biological components, and inactivates their functions. So like ROS and oxidases Substances with oxidative activity can be collectively considered as oxidizing power in the living body.
On the other hand, we are increasing antioxidant power by having various antioxidants to counter this oxidative power. Typical examples are antioxidant enzymes that can eliminate ROS, such as catalase and glutathione peroxidase. In addition, proteins and peptides such as selenoprotein P and glutathione that directly react with ROS to eliminate them. Molecules that suppress the production of ROS by the Fenton reaction by binding to metals, such as transferrin, are also antioxidant proteins. In addition, vitamins with antioxidant activity such as vitamin C and vitamin E ingested from the diet, and components such as carotenoids and polyphenols are also important antioxidants in the living body.
Normally, the body has a good balance of oxidative power and antioxidant power, but if this balance is broken for some reason and it leans to either side, an abnormality will occur in the body. In particular, the situation where the oxidative power exceeds the antioxidant power is called "oxidative stress". Persistently intense oxidative stress, oxidatively modified abnormal proteins and lipids, Nucleic acid cannot be removed, and impaired cell function causes cell death. Induction of even larger cell death causes damage to the tissues that make up it, eventually leading to disease. Oxidative stress includes neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, cardiovascular diseases such as arteriosclerosis, cerebral infarction, and myocardial infarction, renal diseases, and diabetes. Although it has become clear that it is a factor in many diseases, the details of its action on the onset are still unclear, and it is expected that the mechanism of action of oxidative stress in each disease will be elucidated.