الفهرس 
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Abstract
Although NSAIDs are clinically very useful drugs, their prolonged use are known to produce serious tissue damage including gastrointestinal toxicity, nephrotoxicity, hepatotoxicity and cardiovascular toxicity. The present study was performed to evaluate and compare the effects of chronic exposure of normal therapeutic and double therapeutic dose equivalents of ibuprofen and etoricoxib on hematological, biochemical and immunological parameters in rats, correlated by the histopathological examination of liver, kidney, intestine and stomach. One hundred rats were purchased and divided into five equal groups of 20 rats each. The first group served as control, the second group (IBU-20) treated with ibuprofen 20 mg/kg BW, the third group (IBU-40) treated with ibuprofen 40 mg/kg BW, the forth group (ETO-30) treated with etoricoxib 30 mg/kg BW and the fifth group (ETO-60) treated with etoricoxib 60 mg/kg BW. Rats were treated orally once daily for 3 and 6 weeks. Whole blood and serum samples were collected to evaluate some hematological, biochemical and immunological parameters, and liver homogenate for estimation of oxidative stress and antioxidant markers and tissue specimen for histopathological examination. The obtained results revealed that ibuprofen treatment for 3 and 6 weeks caused no significant hematological changes, while etoricoxib treatment only at the end of the 6th week with both doses caused significant increase in RBCs count, Hb and PCV. However, there were no significant changes in erythrocyte indices (MCV, MCH and MCHC), neutrophil count, lymphocyte count, monocyte count, N/L ratio, A/G ratio, GST and GSH by treatment with both drugs. Platelet count showed significant increase in ETO-30 and ETO-60 groups while showed significant decrease in IBU-20 and IBU-40 groups. The leukocyte count, ALT, AST, LDH, creatinine, urea, MDA, INF-γ, IL-1β and TNF-α significantly increased in all treated groups along the experiment, in reverse, uric acid level showed a significant decline in all treated groups compared with the control group. Total protein showed no significant change in etoricoxib treated groups while showed a significant decrease in ibuprofen-treated groups in addition to albumin and globulin, compared with the control group. Catalase enzyme showed a significant decrease in all treated groups compared with the control group. Also, IgM decrease in its levels while IgG showed no significant change, compared with the control group. The presented results that reveal alteration in the renal and hepatic functions beside oxidative damage to the liver are due to the inhibitory actions of NSAIDs on cyclo-oxygenase-1 and/or cyclo-oxygenase-2 enzymes and subsequently the inhibition of prostaglandins. It has been proposed that the therapeutic effects of NSAIDs have been derived from COX-2 (inducible enzyme) inhibition while the undesirable side effects are due to COX-1 (constitutive enzyme) blockade.