RENAL EFFECTS OF SELECTIVE CYCLOOXYGENASE-2 INHIBITORS IN RAT: A LIGHT AND ELECTRON MICROSCOPIC STUDY

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed classes of medication used extensively in the treatment of pain, fever and inflammation. The therapeutic efficacy of NSAIDs is probably mediated through their inhibition of cycle-oxygenase enzyme. Two isoforrns of cycle-oxygenase (COX) had been identified named COX-l and COX-2 (Kujubu et at, 1991; Rossat et at, 1999). A major drawback with nonselective NSAIDs has been the gastrointestinal (GI) erosions, bleeding, salt retention and occasionally acute renal failure. Such drawbacks were now attributed to the inhibition of COX-l (Cryer, 1998; Brater, 1999). Therefore, specific inhibitors of COX-2 were introduce into widespread clinical use in 1999 (Hawkey, 1999). Two selective COX-2 inhibitors celecoxiband rofecoxib
had become the most commonly prescribed medications worldwide. Structurally they both differs, celecoxib incorporates a sulphonamide moiety and have a CF3 group whereas rofecoxib docs not (Wiholm, 2001). Clinical trials using these
medications for treatment of arthritis and pain have uniformly demonstrated efficacy similar to that of nonselective NSAIDs together with marked reduction of GI toxicity and renal side effects (Bombardier et aI., 2000; Silverstein et al., 2000). Previous studies reported that COX-2 enzyme is constitutively expressed in renal tissues. and its expression in that organ can be upregulated in salt depleted animals (Komhoff et al., 1997) and in experimental heart failure (Tomasoni et at, 1998). These observations raised the possibility that selective COX-2 inhibitors rofecoxib and celecoxib may carry the same risk for renal adverse effect as do  nonselective NSAJDs. This was supported by the findings that selective COX-2 inhibitors in salt-depleted subjects induced qualitative changes in renal function similar to those seen with nonselective NSAlDs (Brater et at, 2001). Furthermore, studies comparing rofecoxib and celccoxib with respect to their cardiorenal side effects in hypertensive osteoarthritis patients reported higher frequency of edema and increased systolic blood pressure in patients treated with rofecoxib as compared with celecoxib (Catella-Lawson et al., 2001; Geba et aI., 2001; Hennan et al., 2001; Whelton et al., 2001). The nephropathological changes caused by rofecoxib and celecoxib were describedin two isolated case reports (Rocha and Fernandez-Alonso, 2001; Henao et aI., 2002). However. the patient in the first report was hypertensive and in the second was diabetic and they both received other medication beside the COX-2 inhibitors. Therefore, the purpose of this study was to describe and compare the effects of selective COX-2 inhibitors, cclecoxib and rofecoxih, on the structure of kidney in normal healthy rats using both light and transmission electron microscopy.