Cardiovascular Side Effect Remotely Related to NSAIDs: A Comparative Experimental Study on Albino Rats

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit enzyme cyclo-oxygenase (COX)-1&2, required for antiinflammatory effect, which comes along with side effect of gastric ulceration related to inhibition of COX-1. Whereas recent NSAIDs act selectively on COX-2 isoform. Thus referred as selective NSAIDs. Therefore selective NSAIDs are more beneficial than earlier non-selective NSAIDs in regard of incidence of gastric ulceration. Metabolism of these drugs is associated with liver and kidney. Therefore, we observed the comparative adverse effects of diclofenac sodium (diclo) a non-selective NSAIDs and valdecoxib (valde), a selective NSAIDs on renal function. The experiment was carried on 50 albino rats of duckrey (DR) strain, in equal sex ratio. Animals were divided into five groups (n=10). Group A, B1, B2, C1 & C2. Group A served as control, B1 & B2 were given diclo 5 & 10 mg/kg/day per orally, C1 & C2 were given valde 1 & 2 mg/kg/day per orally respectively, for 30 days. Renal histological examination and biochemical parameters were estimated. We estimated serum creatine, blood urea nitrogen (BUN), uric acid (UA), Na+ & K+ for renal function. Kidney sections of all the groups showed thickening of glomerular basement membrane, increase in glomerular cellularity, and degeneration of proximal and distal convoluted tubule. Tubule in medulla showed degeneration with intraluminal protein exudates. Histopathological changes were more significant with valdecoxib. In biochemical estimation lower dose of diclo showed increase in serum K+ only, on other hand lower dose of valde showed more significant change and there was increase in serum creatine, BUN & K+. Whereas higher doses of diclo and valde showed highly significant increase in serum creatine, BUN & K+. Increased UA was observed only with higher dose of valde. Thus these result show renal insufficiency, fluid overload and accumulation of urea & K+. These can lead to congestive heart failure, pericarditis, hypertension, arrhythmias. Thus, chronic renal failure patient suffers from accelerated atherosclerosis and high incidence of cardiovascular disease can be explained. Valdecoxib though banned due to cardiovascular effects and atherosclerosis which can also linked indirectly from renal insufficiency.