The role of monoamine oxidases in diabetic nephropathy rat model Diabetic nephropathy model

Abstract

Aim: Diabetic nephropathy (DN) is a serious complication that can lead to renal failure in many diabetic patients. Although there are multiple mechanisms related to the pathogenesis of the disease, reactive oxygen species (ROS) play an important role in its etiology. It has been suggested that monoamine oxidases (MAOs) as an intracellularly important ROS source may cause nephropathy by contributing to redox state imbalance in the kidney of diabetics. We investigated the role of monoaminoxidase-A (MAO-A) and monoaminoxidase-B (MAO-B) in the pathogenesis of diabetic nephropathy (DN) induced by streptozotocin (STZ) in rats. We also tried to demonstrate the importance of MAO-A or MAO-B inhibition to prevent the development and progression of DN. Material and Method: Twenty-eight male Wistar albino rats were divided into four groups as normal control and three diabetic groups. A single dose of STZ was given to the peritoneal cavity of rats to induce diabetes. One of the diabetic groups was treated with MAO-A inhibitor(moclobemide, 5 mg/kg/day), another group MAO-B inhibitor, (rasagiline, 10 mg/kg/day), while those included in the DN group were not treated. After the eight-week treatment period, urine samples were collected with a metabolic cage to measure N -acethyl-b-glucosaminidase (NAG), g-glutamyltranspeptidase (GGT), creatinine, glucosuria and proteinuria, and then the animals were anesthetized and sacrificed by cardiac puncture and the kidneys were taken. Blood glucose, BUN, serum creatinine, renal MAO-A, MAO-B, superoxide dismutase (SOD) and catalase (CAT) activity and lipid peroxidation (MDA) were determined by spectrophotometric or ELISA method. Results: The untreated diabetic rats showed nephropathy symptoms such as high serum creatinine, proteinuria, glucosuria and high urinary NAG and GGT. However, renal MAO-A, MAO-B, SOD and CAT activity and MDA levels increased in DN rats. Although moclobemide or rasagiline treatment significantly reduced nephropathic findings and high renal MAO-A and MAO-B activity in diabetic rats, MAO-A inhibition showed more effect than MAO-B. Discussion: The results indicate that the renal MAO-A and MAO-B activity playsan important pathophysiological role, which is responsible for the development and progression of DN, and that MAO-A inhibition is more effective than MAO-B to prevent the formation of DN in diabetic rats.