Effect of Glycosaminoglycan on Proteinuria and Urinary N-acetyl- -D-Glucosaminidase Excretion in Otsuka Long-Evans Tokushima Fatty (OLETF) Rats

Choi, Kyung Mook; Cha, Dae Ryong; Han, Sang Youb; Kim, Dong Rim; Kim, Nan Hee; Baik, Sei Hyun; Choi, Dong Seop

Abstract

BACKGROUND: Increased loss of proteoglycan (PG) characterized by an increased loss of anionic charges in the basement membrane has been considered as one of main factors causing urinary loss of albumin. The glycosaminoglycans (GAGs) are linear polymers of repeated disaccharides and the GAG chains are covalently bound to core proteins, forming proteoglycans. It is known that urinary N-acetyl- -D-glucosaminidase (NAG) excretion is a sensitive marker of renal damage and is increased before other renal functional parameters. The aim of this study was to investigate whether GAG treatment is capable of influencing urinary protein and NAG excretion in Otsuka Long-Evans Tokushima Fatty (OLETF) rats which are known as type 2 diabetic animal model.
METHODS
Fifteen male OLETF rats and twenty male Long-Evans Tokushima Otsuka (LETO) rats were used for this study. LETO rats are non-diabetic control rats. All OLETF rats were randomly assigned to 2 groups: control group (n=10) given only tap water and GAG group (n=5) feeding with GAG 10 mg/kg from 7 weeks to 55 weeks of age. Measurement of body weight, blood glucose, serum BUN and creatinine was performed periodically. 24-hour urine collection for measurement of urinary protein and NAG excretion was done at 17, 25, 37, 46, 55 weeks of age.
RESULTS
1) OLETF rats showed higher body weight, blood glucose, 24-hour urinary protein and NAG excretion compared with LETO rats. But serum concentration of BUN and creatinine were not different between OLETF and LETO rats. 2) GAG-treated OLETF rats exhibited lower urinary protein/creatinine excretion (17.48+/-0.50 vs 22.49+/-0.11 mg/mg Cr, p< 0.05) and NAG (17.40+/-5.94 vs 43.73+/- 7.44 nmol/h/mg Cr, p< 0.05) excretion compared with non-treated OLETF rats. But body weights, blood glucose, serum concentration of BUN and creatinine were not different between GAG-treated OLETF rats and non-treated OLETF rats.
CONCLUSION
1) The urinary excretion of NAG may be a possible early marker of diabetic nephropathy in OLETF rats. 2) Urinary protein and NAG excretion were decreased in the GAG-treated OLETF rats. GAG seems to have a protective effect against development of diabetic nephropathy.