Nephrotoxic effects of celecoxib on adult male albino rats

ABSTRACT

Nonsteroidal anti-inflammatory drugs are widely used for a variety of indications, including acute pain, arthritic pain, and headache. The long-term use of these agents is often limited by unwanted adverse effects, such as gastritis and renal dysfunction. In an effort to decrease the adverse effects while retaining pain-relieving properties, the selective cyclo-oxygenase [COX]-2 inhibitors were developed. The aim of the present study was to evaluate the nephrotoxic hazards of celecoxib and also to evaluate the extent of recovery that occur after discontinuation of this drug during a follow up period .The study was conducted on 50 adult male albino rats weighing approximately [150-200 gm] and divided into 3 groups; group I [negative control group] consisted of 15 rats, each rat was given no medications to evaluate the basic parameters; group II [positive control group [Gum acacia group]] consisted of 15 rats, each rat was gavaged with 2 mL of Gum acacia suspension once daily for 6 weeks and group III [celecoxib group] consisted of 20 rats, each rat was gavaged with 14,4 mg celecoxib/rat once daily for 6 weeks. Twenty four hours after the last dose of celecoxib, 15 rats from each control group and 10 rats from the celecoxib group were used. The kidneys of the rats of these groups were investigated histopathologically by light microscope and biochemically by measuring blood urea nitrogen and serum creatinine, sodium and potassium levels. The remaining rats of celecoxib group were left for another 6 weeks without drug, administration for follow up. At the end of this period the. rats were examined as mentioned above. The main findings of the present study were as follow group 1 [negative control group], and group II [positive control group], showed no abnormal findings without a statistically significant difference between them so we used the results of the negative control group to compare it with those of celecoxib group. As regard biochemical changes, there was an increase in blood urea nitrogen and serum creatinine, sodium and potassium levels in the rats of celecoxib group with a statistically significant difference when compared with the negative control group [P<0.001]. Six weeks after discontinuation of celecoxib administration, the above mentioned biochemical changes improved and showed a statistically significant difference when compared with the results obtained 24 hours after the last dose of celecoxib, but the level of improvement didn't reach to the control level and gave a significant difference when compared with the negative control group. This means that, these parameters improved but didn't return to the level' of the control, which was supported by the histopathological results. As regard histopathological study of celecoxib group, microscopical examination of the kidneys showed severe affection of the kidneys in the form of renal papillary necrosis and acute and chronic tubulo-interstitial nephritis with interstitial oedema and inflammatory cell infiltrate. After 6 weeks of follow-up, histopathological examination of the kidney in the celecoxib group showed incomplete recovery. It could, be concluded that celecoxib is nephrotoxic and its toxic effects were partially reversible after its discontinuation