1998 Fiscal Year Final Research Report Summary
Induction of Connective Tissues Damage Accompanied by Uremia
| Project/Area Number |
08672470
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Physical pharmacy
|
|---|
| Research Institution | CHIBA UNIVERSITY |
|---|
Principal Investigator |
KOSHIISHI Ichiro Chiba University, Pharmaceutical Sciences, Research associate, 薬学部, 助手 (20170235)
|
|---|
| Project Period (FY) |
1996 – 1998
|
| Keywords | Uremia / Cyanate / Dehydroascorbate / Ascorbate / Connective tissues / Extracellular matrix / Oxidative stress / Collagen |
|---|
| Research Abstract |
In the patients with uremia, a high amount of cyanate is produced from urea through the simultaneous degradation. We found a novel reaction between cyanate and dehydroascorbate under physiologic conditions, producing carbamylated dehydroascorbate derivative (CDA), Through the investigations on the structure of CDA, it appeared to be a novel biological substance. We established a method for the determination of CDA in biological samples. When we applied the present method to biological fluids including plasma and urine, it appeared that CDA exists in the urine samples collected from the normal humans. Furthermore, we established a method for the simultaneous determination of ascorbate and dehydroascorbate in biological samples. By using this method, we investigated the effect of cyanate on the ascorbate- dehydroascorbate redox cycle in vivo. Consequently, we found a fact that cyanate causes depletion of ascorbate in organisms under the oxidative stress. In general, the patients with uremia suffer from the anemia caused by the deficiency of erythropoietin, which is synthesized by interstitial cells in kidney. Erythrocytes play a significant role in the detoxication of oxidative substances, so that the decrease of erythrocytes is responsible for the oxidative stress. These facts suggest that cyanate produced from urea decreased the ascorbate level in vivo through the mechanism described above.
Ascorbate is an essential element for the collagen synthesis by connective tissue cells. The ascorbate deficiency is a possible factor for the construction of the fragile connective tissues in patients with uremia.
|
