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, AT1 receptor, and transforming growth factor-β1. Treatment with the selective cyclooxygenase-2 inhibitor celecoxib reduced the urinary excretion of prostaglandins such as prostaglandin E2, 6-keto prostaglandin F1α, and thromboxane B2. Kidney hypertrophy was reversed by the treatment, and the renal expression of cyclooxygenase-2, AT1 receptor, and transforming growth factor-β1 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 AT1 receptors and transforming growth factor-b1 in the kidney.
Highlights
Diabetes mellitus (DM) is a chronic disease caused by an absolute or relative deficiency in insulin production by the pancreas and with or without resistance to insulin [1, 2]
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
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 AT1 receptors and transforming growth factor- 1 in the kidney
Summary
Diabetes mellitus (DM) is a chronic disease caused by an absolute or relative deficiency in insulin production by the pancreas and with or without resistance to insulin [1, 2]. Vascular and parenchymal damage of the kidneys lead to diabetic nephropathy, which is the first cause of end-stage renal disease requiring dialysis. Metabolic and hemodynamic changes have been involved in the development of this pathologic condition, and among them, increased kidney size and elevated glomerular filtration rate (GFR) seem to be some of the most relevant [4]. These alterations start before any measurable clinical changes, and are characterized by tubular and glomerular hypertrophy, thickening of glomerular basement membrane and progressive glomerular accumulation of extracellular matrix components. The increase in GFR results in glomerular hyperfiltration and is the central tenant for eventual glomerular damage and later down stream complications [4,5]
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