Alteration of urinary sorbitol excretion in WBN-kob diabetic rats - treatment with an aldose reductase inhibitor

Abstract

An accerelated polyol pathway in diabetes contributes to the development of diabetic complications. To elucidate diabetic nephropathy involving also renal tubular damage, we measured urinary sorbitol concentration concomitantly with urinary N-acetyl--glucosaminidase (NAG) excretion in WBN-kob diabetic rats.Twenty-four-hour urinary sorbitol concentrations increased in the diabetic rats in parallel with whole blood sorbitol concentrations. An increase in 24-h urinary NAG excretion coincided with the elevated urinary sorbitol levels in the diabetic rats.The administration of epalrestat, an aldose reductase inhibitor, reduced the increased whole blood and urinary sorbitol concentrations and urinary NAG excretion concomitantly with renal aldose reductase inhibition in the diabetic rats.These results indicate that diabetic nephropathy involves distorted cell function of renal tubules, and that treatment with epalrestat may prevent at least the progress of the nephropathy.

Protective Effects of Bendazac Lysine on Diabetic Peripheral Neuropathy in Streptozotocin‐induced Diabetic Rats

“…Bendazac lysine (BDL) was provided by Supereyes Pharmaceutical (Pinghu, China) and suspended in 1% carboxymethyl cellulose (CMC) at different concentrations (1.0, 2.0 and 4.0%). Epalrestat (EPS) was kindly donated by Yangtze River Pharmaceutical Group (Taizhou, China) and served as a positive control drug suspended in 1% CMC 14,15 . Streptozotocin was purchased from Biomol Research Laboratory (Plymouth Meeting, PA, USA).…”

The aldose reductase inhibitor epalrestat exerts nephritic protection on diabetic nephropathy in db/db mice through metabolic modulation

“…As AR is the ratecontrolling enzyme in the polyol pathway, epalrestat can significantly inhibit AR and downregulate polyol metabolites (such as sorbitol and fructose) to alleviate osmotic stress [1]. Except for diabetes neuropathy, recent accumulative evidence has suggested the potential application of ARIs for renal protection in DN [12,13]. Li et al [14] observed significant depletion of myoinositol in the renal cortex of diabetic kidneys in db/db mice, which is observed in other animal models [15,16].…”

Health effects of kiwi wine on rats: an untargeted metabolic fingerprint study based on GC-MS/TOF

“…The level of metabolites excreted reects both the adequacy of the diet and the degree of body health, especially for 2-oxoglutarate, 61 although there is no direct evidence to link the declined excretion of these metabolites with health. According to previous studies, the increased excretion of 2-oxoglutarate, sorbitol and glucose are related to metabolism-associated diseases like diabetes, 61,62 interstitial cystitis/painful bladder syndrome, 63 gastric cancer, 64 and polycystic kidney disease. 65 Moreover, Ekblond et al 66 have proposed that the declined levels of urinary glucose excretion might serve as an evaluation factor for health protection.…”