Minocycline with Aspirin: An Approach to Attenuate Diabetic Nephropathy in Rats

Abstract

Degradation of extracellular matrix (ECM) by enhanced production of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in diabetes leads to nephropathy. Cyclooxygenases (COX) further increase levels of these MMPs. The objective of present study was to inhibit MMP-2 and MMP-9 by combination of minocycline and aspirin to treat diabetic nephropathy. Diabetes was induced in male Wistar rats by streptozotocin (STZ, 55 mg/kg i.p.). Four weeks after diabetes induction, the rats were treated with minocycline (50 mg/kg, p.o.), aspirin (50 mg/kg, p.o.), or minocycline (50 mg/kg, p.o.) plus aspirin (50 mg/kg, p.o.) for a period of 4 weeks. At the end of eighth week fluid input, urine output, and renal function tests were carried out for diagnosis of diabetic nephropathy. Renal hypertrophy was measured and histopathology was done to evaluate renal damage. Diabetes produced significant loss of body weight, polyuria, polydipsia, hyperglycemia, and increase in blood pressure. Serum creatinine, urea, and blood urea nitrogen levels were found to be increased significantly in the STZ group diabetic rats. Treatment with combination of minocycline and aspirin significantly prevented the rise in creatinine, urea, and blood urea nitrogen levels and increased creatinine clearance. Image analysis of kidneys revealed that collagen level was significantly decreased in combined treated group when compared with control. Results of present study suggest that MMP-2 and MMP-9 inhibition in presence of COX inhibitor prevents the development of experimental diabetic nephropathy in rats and can be a potential approach for the treatment.

• extracellular matrix
• diabetic nephropathy
• matrix metalloproteinase-2
• matrix metalloproteinase-9