2003 Fiscal Year Final Research Report Summary
The effects of selective cyclooxygenase-2 inhibitor on fetal ductus arteriosus and kidney
| Project/Area Number |
12557086
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 展開研究 |
|---|
| Research Field |
Embryonic/Neonatal medicine
|
|---|
| Research Institution | Akita University |
|---|
Principal Investigator |
HARADA Kenji Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (20221509)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAMURA Masamichi Akita University, School of Medicine, Research Associate, 医学部, 助手 (10270844)
|
|---|
| Project Period (FY) |
2000 – 2003
|
| Keywords | Ductus arteriosus / kidney / Fetus / COX-2 inhibitor |
|---|
| Research Abstract |
Background : Recent studies demonstrated that selective COX-2 inhibitors constrict the fetal ducus arteriosus (DA) as non-specific COX inhibitors, like indomethacin (IND). We previously reported renal tissue damage in fetal rats induced by maternally administered IND. To evaluate whether a maternally administered selective COX-2 inhibitor, celecoxib, causes morphological renal damages in fetal rats and to evaluate the relation to the fetal DA constriction. Methods : JND (10mg/kg), celecoxibs (10-60mg/kg) and vehicles were administered orally to the pregnant rats on the 20^<th> day of gestation. The fetuses were removed 24 hours after and were divided into two study groups. In the DA constriction study, rapid whole body freezing method was used to obtain the inner diameter ratio of the DA to the main pulmonary artery (DA/PA). In morphological study, the kidneys were removed and examined histopathologically. The data was statistically compared by non-parametric analysis. Result : Celecoxibs constricted the fetal DA dose-dependently (10 mg: 0.92 ± 0.02、20 mg: 0.65 ± 0.12、30 mg: 0.35 ± 0.08、40 mg: 0.31 ± 0.11、50mg: 0.17 ± 0.10、 60 mg: 0.11 ± 0.04). Celecoxibs produced a variety of corticomedullary necrosis and of collapse in distal and proximal tubules in the fetal kidney. IND produced the similar but more severe morphological damages. Conclusion : These data suggested that a selective COX-2 inhibitor, celecoxib, causes morphological tissue damages in fetal rats, like indomethacin, and that these damages are indepen of the fetal DA constriction.
|
