Effects of Lipoxygenase Inhibitor on Diabetic Nephropathy in Rats: Decreasing Proteinuria and Preserving Renal Function / 대한신장학회지

ABSTRACT

PURPOSE: Oxidative stress leads to an increased production of lipoxygenase derivatives in diabetic nephropathy. Thus, we hypothesized that lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), ha the effects of decreasing proteinuria and preserving renal function in streptozotocin (STZ)-induced diabetic rats. METHODS: 45 Sprague-Dawley rats were divided into three groups; (A) treatment with lipoxygenase inhibitor, NDGA in diabetic nephropathy rats, (B) treatment with dimethyl sulfoxide (DMSO) as a vehicle in STZ-induced diabetic rats, (C) normal control group with subcutaneous injection of normal saline. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats of group A and B. After the 4th week of STZ injection, NDGA (10 mg/kg) and DMSO were given subcutaneously for another 4 weeks in group A and B respectively. RESULTS: The NDGA-treated diabetic rats exhibited significantly decreased urinary albumin excretion. Serum creatinine and blood urea nitrogen concentrations were increased in both group A and B, and tend to be higher in group B than group A. Twenty-four-hour urine creatinine clearances were increased in both group A and B after injection of STZ. Pathologic alterations of kidney were observed after injection of STZ, and then attenuated after administration of NDGA. CONCLUSION: These results suggest the potential of lipoxygenase inhibitor as a complementary therapy for the prevention and treatment of diabetic nephropathy.