The effects of celecoxib, a COX-2 selective inhibitor, on acute inflammation induced in irradiated rats

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 gamma-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-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), LTB(4), PGE(2) (as an index of COX-2 activity), TXB(2) (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-1beta, TNF-alpha, LTB(4), PGE(2), but lacked any significant effect on TXB(2) 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.

Phytochemical study, cytotoxic, analgesic, antipyretic and anti-inflammatory activities of Strychnos nux-vomica

“…So, it is important to examine the cytotoxic activities of the extract beside its anti-inflammatory activity. Many previous researchers have also revealed that carrageenan injection resulted in lipid peroxidation and oxidative stress in the inflamed paw, which could be inhibited by many tested anti-inflammatory compounds (Liao et al 2013;Khayyal et al 2009). …”

The Association of IFI27 Expression and Fatigue Intensification during Localized Radiation Therapy: Implication of a Para-Inflammatory Bystander Response

“…RNA extraction, purification, cDNA and cRNA synthesis, amplication, hybridization, scanning, and data analyses were conducted following standard protocols as previously described [42]. Summary of Affymetrix microarray chips (HG U133 Plus 2.0, Santa Clara, CA, USA), normalization of raw signal intensity values, transformation of quantile normalization value, detection of outliers, and statistical methods used followed the same procedures that were previously described [14]. The most up-regulated gene was selected for confirmation by quantitative real time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA).…”

“…In radiation therapy, release of reactive oxygen species and reactive nitrogen species during irradiation induces detrimental cellular damage, not only to irradiated cells but also to non-targeted cells that receive signals from irradiated cells, causing short and long term bystander effects through cytokine stimulation to respond to tissue damage [12]. There is a growing area of research asserting that cancer- and cancer-treatment related fatigue is driven by pro-inflammatory cytokines (e.g., IL-6, IL-1β, TNF-α) and inflammatory pathways (e.g., CRP, IL-1RA) as observed using animal [13,14] and clinical models [6,15]. A recent review characterized the inflammatory response from bystander cells as a para-inflammatory response to low dose radiation [16].…”

The influence of irradiation on the potential chondroprotective effect of aqueous extract of propolis in rats

“…Exposure to ionising radiation has been shown to exaggerate inflammatory responses and to enhance the release of inflammatory mediators in rats (El-Ghazaly et al 1985, Khayyal et al 2009. It was also shown that ionising radiation affects growing rather than mature cartilage (Schmitt andZamboglou 1990, Cornelissen et al 1996).…”