OBJECTIVETo investigate the renal protective effects of sulodexide and its anti-oxidative stress mechanism in diabetic rats.

METHODThirty male SD rats were randomized into 3 equal groups, namely the control group, diabetic group, and sulodexide treatment group. Twelve weeks after establishment of rat diabetic models and administration of sulodexide, the rats were sacrificed for measurement of the urine volume, body mass, kidney mass/body weight ratio, plasma glucose, and glycosylated hemoglobin (HbA1c). Malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) activities in the renal tissue or serum were tested. Electron microscopy was performed to observe the pathological changes in the kidneys.

RESULTSThe urine volume, renal mass/body mass ratio, serum glucose, HbA1C, and serum and renal MDA levels all significantly increased in the diabetic rats in comparison with the normal controls (P<0.05). But the body weight and activities of SOD, CAT, and GSH-PX in the renal tissue in the normal control group were significantly higher than those in the diabetic and sulodexide group. After 12 weeks of sulodexide treatment, SOD, CAT, and GSH-PX activities in the renal tissue of rats were significantly increased in comparison with those in the diabetic rats (P<0.05). Electron microscopy showed obvious irregular thickening of the glomerular capillary basement membrane in the diabetic group with vacuolization in the mitochondria in the epithelial cells, and such pathological changes were significantly alleviated in the sulodexide treatment group.

CONCLUSIONSSulodexide can effectively lower the urinary albumin excretion rate, improve the ultrastructural renal pathologies and prevent glomerular basement membrane thickening in diabetic rats, probably in association with the reduction of the MDA levels and enhancement of SOD, CAT, and GSH-PX activities.