期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 300, 期 6, 页码 H2316-H2322出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01259.2010
关键词
cyclooxygenase-2 inhibition; kidney
资金
- National Heart, Lung, and Blood Institute [HL-25394]
Quilley J, Santos M, Pedraza P. Renal protective effect of chronic inhibition of COX-2 with SC-58236 in streptozotocin-diabetic rats. Am J Physiol Heart Circ Physiol 300: H2316-H2322, 2011. First published March 25, 2011; doi: 10.1152/ajpheart.01259.2010.-The induction of renal cyclooxygenase-2 (COX-2) in diabetes has been implicated in the renal functional and structural changes in models where hypertension or uninephrectomy was superimposed. We examined the protective effects of 3 mo treatment of streptozotocin-diabetic rats with a highly selective COX-2 inhibitor (SC-58236) in terms of albuminuria, renal hypertrophy, and the excretion of TNF-alpha and TGF-beta, which have also been implicated in the detrimental renal effects of diabetes. SC-58236 treatment (3 mg . kg(-1) . day(-1)) of diabetic rats resulted in reduced urinary excretion of PGE2, 6-ketoPGF(1 alpha), and thromboxane B-2, all of which were increased in the diabetic rat compared with age-matched nondiabetic rats. However, serum thromboxane B2 levels were unchanged, confirming the selectivity of SC-58236 for COX-2. The renal protective effects of treatment of diabetic rats with the COX-2 inhibitor were reflected by a marked reduction in albuminuria, a reduction in kidney weight-to-body weight ratio, and TGF-beta excretion and a marked decrease in the urinary excretion of TNF-alpha. The protective effects of SC-58236 were independent of changes in plasma glucose levels or serum advanced glycation end-product levels, which were not different from those of untreated diabetic rats. In an additional study, the inhibition of COX-2 with SC-58236 for 4 wk in diabetic rats resulted in creatinine clearance rates not different from those of control rats. These results confirm that the inhibition of COX-2 in the streptozotocin-diabetic rat confers renal protection and suggest that the induction of COX-2 precedes the increases in cytokines, TNF-alpha, and TGF-beta.
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