TITLE:
Effect of Cyclooxygenase-2 Blockade on Renal Hypertrophy Development during Early Diabetes Mellitus
AUTHORS:
Beatriz Vázquez-Cruz, Josseline Rangel-Veladiz, David Segura-Cobos, Pedro López-Sánchez, Maximiliano Ibarra-Barajas, Dante Amato
KEYWORDS:
COX-2; Prostaglandins; TGF-β; Diabetic Nephropathy; Renal Hypertrophy; Angiotensin II
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.4 No.3,
May
31,
2013
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.