[Extract of Ginkgo biloba and alpha-lipoic acid attenuate advanced glycation end products accumulation and RAGE expression in diabetic nephropathy rats].

OBJECTIVE

To investigate the accumulation of advanced glycation end products (AGEs) and expression of receptor for AGEs (RAGE) in streptozocin (STZ)-induced diabetic nephropathy in rats, and the role of antioxidants on the AGEs-RAGE signaling.

METHODS

Diabetic rats were induced by once intraperitoneal injection of STZ at the dose of 60 mg/kg, and randomly divided into the DN group (n=12, treated with normal saline by intraperitoneal injection, once daily), the extract of Ginkgo biloba (EGb) group (n=14, treated with EGb 300 mg/kg by oral administration, once every other day), and the alpha-lipoic acid (ALA) group (n=12, treated with ALA at the dose of 35 mg/kg by intraperitoneal injection, once every other day). Rats of the normal control group (n=10) were given vehicle citrate buffer at the dose of 60 mg/kg. Rats were sacrificed at the 12th week and the 20th week of this study. The four groups were compared in terms of body weight, blood glucose, renal function, 24-h urine protein. Renal pathological changes were observed by PAS staining. Oxidative stress indices were detected using spectrophotometry. The concentrations of AGEs were measured using fluoro spectrophotometry, and the expressions of RAGE were detected by Real-time PCR and Western blot.

RESULTS

Compared with the normal control group, the 24-h urine protein quantitation was higher and the glomerular filtration rate increased in rats at the 12th week and the 20th week. The pathological tissue staining showed dilated glomerular mesangium, proliferated glomerular matrix, vacuolar degeneration of the renal tubular epithelium. Malonaldehyde (MDA) levels and 8-hydroxide radical guanine deoxyriboside (8-OHdG) levels increased, and catalase (CAT) and reduced glutathione hormone (GSH) levels decreased. The AGEs contents in serum and renal tissue homogenate increased. The expressions of RAGE mRNA and protein increased in the DN group at the 12th and the 20th week. The 24-h urine protein quantitation was reduced in the EGb group and the ALA group, with alleviated pathological changes, lowered MDA and 8-OHdG levels, increased CAT and GSH levels, decreased AGEs contents, and down-regulated RAGE expressions.

CONCLUSIONS

AGEs contents increased and RAGE expression up-regulated in the circulation and local renal tissues in DN rats. EGb and ALA could inhibit AGEs production and down-regulate RAGE expressions by reducing oxidative stress, thus further improving the renal tissue structure and renal functions of DN rats. It had better application prospect in treatment and prevention of DN.