Differential regulation of prostacyclin and thromboxane by dexamethasone and celecoxib during oxidative stress in newborn rabbits.
To compare the effects of dexamethasone (Dex) and celecoxib (Cel) on F-isoprostane, prostacyclin (PGI2), and thromboxane A2 (TxA2) following hyperoxia, and hyperoxia followed by recovery in room air (RA), newborn rabbits were exposed to hyperoxia (80-100% oxygen) for 4 days, during which they were treated with saline (Sal, i.m.), Dex (i.m.), vehicle (Veh, PO), or Cel (PO, n = 12 per group). Six animals in each group were sacrificed immediately following hyperoxia, and the remainder allowed to recover in RA for 5 days. The control litters were treated simultaneously in RA with all conditions other than atmospheric oxygen being identical. Blood samples were assayed for 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), 6-keto prostaglandin F1alpha (6-ketoPGF1alpha), and TxB2. Dex and Cel decreased 8-epi-PGF2alpha during hyperoxia and the recovery period. Dex increased 6-ketoPGF2alpha following hyperoxia, while similar increments were noted during recovery with Cel. Although TxB2 was decreased only during the recovery period, TxB2/6-ketoPGF1alpha ratio was lower during hyperoxia and recovery in both treated groups. The effect of Cel on 8-epi-PGF2. and TxA2/PGI2 ratio confirm the formation of a COX-derived F2-isoprostane that is possibly linked to TxA2 receptors. Further studies are required to examine whether Cel can be used as a therapeutic alternative to Dex for oxygen-induced injury in the newborn.
Ozaki
Naomi
N
Department of Pediatrics, University of California, Irvine Medical Center, Orange, USA .
Beharry
Kay
K
Nishihara
Kenji C
KC
Akmal
Yasir
Y
Ang
Jorge G
JG
Modanlou
Houchang D
HD
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000068579:Celecoxib; D003907:Dexamethasone / Q000009:adverse effects / Q000494:pharmacology*; D015237:Dinoprost / Q000031:analogs & derivatives*; D011464:Epoprostenol / Q000378:metabolism*; D028441:F2-Isoprostanes / Q000097:blood; D018496:Hyperoxia / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011720:Pyrazoles; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D028441:F2-Isoprostanes; D011720:Pyrazoles; D013449:Sulfonamides; C075750:8-epi-prostaglandin F2alpha; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003907:Dexamethasone; D015237:Dinoprost; D011464:Epoprostenol; D000068579:Celecoxib