الفهرس 
Introduction and aim of the work
Materials and methodsOnly 14 pages are availabe for public view
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Abstract
Diabetic nephropathy is a major microvascular complication of diabetes and eventually leads to end-stage renal disease. Detailed understanding of the diabetic renal injury focused the light on new renoprotective strategies. Thus the present study designed to evaluate the renal effects of celecoxib and enalapril on the progression of renal injury in experimental model of diabetic nephropathy on three levels of interventions (prophylactic; immediately, early therapeutic; 2 weeks, and late therapeutic; 8 weeks after induction of diabetes). Drug treatment was completed to 16 weeks after induction of diabetes at 3 levels. The study was carried out on control and STZ-induced diabetic rats fed on high protein diet (50%) for 16 weeks. Diabetic rats were classified into three groups; prophylactic groups, Early treated groups, and Late treated groups. Each group was further classified into four equal subgroups; Diabetic control group, celecoxib, enalapril, and combination groups. Kidney functions tests, microalbuminuria, renal MDA, GSH content, SOD activity, and renal histopathology examination (LM) using Hx&E, PAS, and silver stains for: GSI, TIS, and vascular lesion score were used to assess the effect of tested drugs. STZ-induced diabetes led to development of diabetic nephropathy associated with increased oxidative stress. Both selective COX-2 inhibitor, celecoxib, and ACE inhibitor, enalapril, both prophylactic and early in the disease process produced comparable level of renoprotection manifested by significant decrease of serum creatinine and microalbuminuria, which was accompanied by significant decrease of renal MDA content, significant increase of renal GSH content and SOD activity. Glomerulosclerosis seen in untreated-diabetic group were prevented by both celecoxib and enalapril. Combination therapy was superior in renoprotective effect at the prophylactic or early therapeutic levels by biochemical and histopathological evaluation. The favorable renal effect observed with celecoxib or enalapril could be partially explained by antioxidant activity; however, this does not exclude the contribution of anti-inflammatory and/or hemodynamic effects for either celecoxib or enalapril respectively. Administration of celecoxib or enalapril as late therapeutic intervention (after the development of diabetic structural renal lesions) did not reverse or retard the progression of glomerulosclerosis. The effects of delayed combination therapy were more hazardous (higher serum creatinine) than either agent alone at this level of intervention. Finally, in the light of the results of this study, the ACE inhibitor plus COX-2 inhibitor combination may be beneficial in treatment of diabetic renal disease and their effect depends on the phase of the disease at which treatment is started.