The effects of celecoxib, a COX-2 selective inhibitor, on acute inflammation induced in irradiated rats |
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Authors: | M T Khayyal Mona A El-Ghazaly R M El-Hazek A S Nada |
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Institution: | (1) Drug Radiation Research Department, National Centre for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt;(2) Pharmacology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; |
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Abstract: | The potential value of selective and non-selective COX-2 inhibitors in preventing some of the biochemical changes induced
by ionizing radiation was studied in rats exposed to carrageenan-induced paw edema and 6-day-old air pouch models. The animals
were exposed to different exposure levels of γ-radiation, namely either to single doses of 2 and 7.5 Gy or a fractionated
dose level of 7.5 Gy delivered as 0.5 Gy twice weekly for 7.5 weeks. The inflammatory response produced by carrageenan in
irradiated rats was markedly higher than that induced in non-irradiated animals, and depended on the extent of irradiation.
Celecoxib, a selective COX-2 inhibitor, in doses of 3, 5, 10, and 15 mg/kg was effective in reducing paw edema in irradiated
and non-irradiated rats in a dose-dependent manner as well as diclofenac (3 mg/kg), a non-selective COX inhibitor. Irradiation
of animals before the induction of the air pouch by an acute dose of 2 Gy led to a significant increase in leukocytic count,
as well as in the level of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), LTB4, PGE2 (as an index of COX-2 activity), TXB2 (as an index of COX-1 activity), and the plasma level of MDA. This increase in level of these parameters was more marked
than that observed in the non-irradiated animals subjected to the inflammagen. The blood GSH level was not affected by the
dose of irradiation used, whereas superoxide dismutase (SOD) activity was suppressed. In many respects, celecoxib (5 mg/kg)
was as potent as diclofenac in decreasing the elevated levels of IL-6, IL-1β, TNF-α, LTB4, PGE2, but lacked any significant effect on TXB2 level. Since it is mostly selective for COX-2 with a rare effect on COX-1 enzyme, both drugs at the selected dose levels
showed no effect on level of MDA, GSH, and SOD activity. |
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