Effect of selective COX-2 inhibitor, celecoxib on adjuvant-induced arthritis model in irradiated rats.
OBJECTIVE
The potential value of celecoxib was compared to a standard non-steroidal anti-inflammatory drug (NSAID), diclofenac in the adjuvant-induced arthritis (AIA) model in rats as a model of chronic inflammation under the influence of ionising radiation.


METHODS
Various inflammatory mediators and biochemical parameters were measured in the arthritic rats under the influence of ionising radiation.


RESULTS
Exposure of the animals to a radiation dose of 2 Gy before inoculation of the adjuvant led to a marked increase in the paw volume reaching ca. 70% more than that in non-irradiated ones as well as a significant increase in the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), prostaglandin E₂ (PGE₂) as an index of cyclooxygenase-2 (COX-2) activity, thromboxane B₂ (TXB₂) as an index of cyclooxygenase-1 (COX-1) activity and plasma level of malondialdehyde (MDA). The blood glutathione (GSH) level was not affected by the dose of irradiation used while superoxidedismutase (SOD) activity was reduced. Treatment with celecoxib in a dose of 5 mg/kg was effective in decreasing the elevated levels of IL-6, IL-1β, TNF-α, PGE₂ whereas it lacked any effect on TXB₂ level since it had hardly any effect on COX-1 enzyme. Both drugs at the selected dose levels showed no effect on level of MDA, GSH and SOD activity.


CONCLUSIONS
Irradiation of animals caused a marked change in the inflammatory response in AIA model of inflammation. Both celecoxib and diclofenac were nearly equipotent in suppressing the inflammatory response in both normal and irradiated rats. Accordingly, since the inhibition of COX-1 by traditional NSAID is thought to have undesirable side-effects on proliferating tissues, it would seem preferable to use selective COX-2 inhibitors to limit such deleterious effect.
El-Ghazaly
Mona A
MA
Drug Radiation Research Department, National Centre for Radiation Research & Technology, Atomic Energy Authority, Nasr City, Cairo, Egypt. monaghazaly@hotmail.com
Nada
Ahmed S
AS
El-Hazek
Rania M
RM
Khayyal
Mohamed T
MT
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004008:Diclofenac / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014916:Whole-Body Irradiation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D011720:Pyrazoles; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D004008:Diclofenac; D000068579:Celecoxib