Effect of Cyclooxygenase-2 Blockade on Renal Hypertrophy Development during Early Diabetes Mellitus

Abstract

Diabetes mellitus is the leading cause of diabetic nephropathy; the early phase of diabetes is associated with kidney growth and hyperfiltration; several factors modulate these changes, among them, prostaglandins and angiotensin II. Previous studies have shown that cyclooxygenase-2 is implicated in experimental models of diabetes. The aim of this work was to study the effect of celecoxib treatment on renal hypertrophy development in early diabetes mellitus. In our rats with early streptozotocin-induced diabetes there was renal hypertrophy, and increased renal expression of cyclooxygenase-2, AT 1 receptor, and transforming growth factor-β 1 . Treatment with the selective cyclooxygenase-2 inhibitor celecoxib reduced the urinary excretion of prostaglandins such as prostaglandin E 2 , 6-keto prostaglandin F 1α , and thromboxane B 2 . Kidney hypertrophy was reversed by the treatment, and the renal expression of cyclooxygenase-2, AT 1 receptor, and transforming growth factor-β 1 decreased. The renoprotective effects of celecoxib were independent of the changes in plasma glucose levels. These results confirm that cyclooxygenase-2 inhibition in rats with streptozotocin-induced diabetes decrease renal hypertrophy; this effect in turn, may be mediated by reduction of the expression of AT 1 receptors and transforming growth factor- 1 in the kidney.

Morphology and cyclooxygenase-2 and renin expression in the kidney of young spontaneously hypertensive rats

“…Others showed that COX-2 overexpression is involved in progressive renal injury in a model of nephropathy induced by renal ablation in rats, since the chronic inhibition of COX-2 attenuates the damage, reducing glomerular hypertension, and renal inflammation. 14 Similarly, treatment with celecoxib, a selective COX-2 inhibitor, prevented the increase in the cellular area in proximal tubules and renal protein/DNA ratio in diabetic rats, 59 indicating that COX-2 is involved in the development of renal hypertrophy in diabetes. Additionally, it was reported that COX-2 promotes mesangial cell proliferation in culture under stress conditions.…”