New findings suggest altered kidney regulation of COX-2 occurs at very early stage in obesity-related diabetic nephropathy
In human diabetic patients, an excessive vasoconstrictive and pro-aggregatory thromboxane (TXA2) renal synthesis, along with a decrease in vasodilatory and anti-aggregatory prostaglandin (PGE2) synthesis, has been found to influence kidney function. Prostaglandins and thromboxane are formed by the enzymatic oxidation of arachidonic acid catalyzed by the cyclooxygenases, COX 1 and COX-2. Recently developed non-steroidal anti-inflammatory drugs (NSAIDS) are targeted to inhibit COX-2 and treat inflammation and arthritic pain. It is not known if the use of NSAIDS may be beneficial for the treatment of kidney disease; however, the upregulation of pro-inflammatory COX-2 and increased production of COX-2 derived metabolites have been implicated in diabetic nephropathy. COX-2 regulation and its association with renal damage are not known in the Obese Zucker rat. A new study tests the hypothesis that altered kidney regulation of COX-2 occurs at a very early stage in the progression of kidney disease.
A New Study
Obesity is a major risk factor that, along with hyperglycemia and hypertension, contributes to the progression of kidney disease. Previous studies in models of Type I diabetes have suggested that COX-2 may contribute to diabetic nephropathy. In this study researchers found increases in renal COX-2 levels and changes in TXA2 and PGE2 levels in the Obese Zucker rat. The changes in TXA2 and PGE2 are similar to those found in the diabetic patient population.
Interestingly, these changes occurred in the Obese Zucker rat at pre-hyperglycemic and pre-hypertensive stages. Renal damage was minimal at 10-12 weeks of age and progressed rapidly towards kidney failure by 20-21 weeks of age. Therefore, during the development of obesity-related diabetes, alternations in COX-2 derived metabolites could contribute to the renal damage associated with this disease. Taken as a whole, these findings suggest that COX-2 inhibitors may be beneficial for the prevention of renal damage in obesity-related type II diabetes.
The American Physiological Society (APS) is one of the worlds most prestigious organizations for physiological scientists. These researchers specialize in understanding the processes and functions by which animals live, and thus ultimately underlie human health and disease. Founded in 1887 the Bethesda, MD-based Society has more than 11,000 members and publishes 3,800 articles in its 14 peer-reviewed journals each year.
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Meeting Dates: October 1-4, 2003
Radisson Riverfront Hotel and Convention Center, Augusta, GA
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