The Role of TNF-alpha in the Progression of Diabetic Nephropathy

Overview

Diabetic nephropathy (DN) is one of the major causes of end stage renal disease. Recent studies suggest that renal inflammation is critical for the development of DN. TNF-alpha is inflammatory cytokine that has been used as a marker and predictor of chronic renal disease. In preliminary studies, we observed that the renal expression of TNF-alpha was elevated in Dahl salt-sensitive (SS) rats with streptozotocin (STZ, type-1 diabetic model). Therefore, the current study examined whether chronic blockade of TNF-alpha with Etanercept (ETN) would prevent the progression of renal injury in STZ-treated SS rats. This study was performed on 9 week-old SS rats which were placed in metabolic cages for a 24hr-urine collection to determine baseline protein excretion. Blood samples were also taken from the tail for the measurement of glucose levels. Then, the rats were injected with STZ (50 mg/kg, i.p.) and protein excretion was measured every 3 weeks until 9 weeks of diabetes was completed. After 3 weeks of diabetes (3 weeks post STZ injection), rats were divided into two treatment groups: (1) vehicle and (2) ETN (0.8 mg/kg twice a week, s.c.) and treated for 6 weeks. After 3 weeks of diabetes, protein excretion increased from 78±5 to 234±46 mg/day. Treatment with ETN reduced protein excretion by 20%. Administration of ETN had no effect on glucose levels and the values were similar to those obtained from vehicle-treated diabetic SS rats. These data indicate that ETN may be a beneficial therapy for the progression of DN.

Competition history

• ISEF 2014 Mathematics · Entry ME053

Resources

• ISEF abstract page ↗

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