Effects of an aldose reductase inhibitor on gastroenteropathy in streptozotocin-diabetic rats.
We investigated the effects of epalrestat, an aldose reductase inhibitor (ARI), on gastric emptying, fecal water content, and electrolyte transport in distal colon in streptozotocin (STZ)-induced diabetic rats. We measured gastric emptying time by acetaminophen method and short-circuit-current (Isc) in colonic mucosa using an Ussing chamber. The Isc in response to electric-field-stimulation (EFS) was decreased in untreated rats due to suppression by Cl- secretion. ARI treatment alleviated this suppression (2.7 +/- 0.6 vs. 7.4 +/- 1.1 microA/0.38 cm2 at 8 weeks after treatment, 1.1 +/- 0.2 vs. 7.0 +/- 1.0 at 12 weeks after treatment, P<0.05). In addition, the percentage of fecal water content in untreated rats was significantly lower than in ARI-treated rats (58.0 +/- 2.0 vs. 67.6 +/- 0.8% at 8 weeks, 56.9 +/- 2.1 vs. 63.4 +/- 1.4 at 12 weeks, P<0.05). From STZ injection to 8 weeks, the serum levels of acetaminophen in the diabetic rats were significantly lower than in controls, indicating delayed gastric emptying. At 12 weeks in the diabetic rats treated with ARI, the serum levels of acetaminophen were significantly higher than in the untreated diabetic rats (6.6 +/- 0.4 vs. 3.5 +/- 0.5 microg/ml, P<0.05). ARI-treatment ameliorated delayed gastric emptying without improving glycemic control. These findings show that ARI partially prevented progression of impaired gastric emptying, ion transport, and water transport, and suggest that epalrestat might be useful in the treatment of diabetic gastroenteropathy.
Oya
M
M
Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, 54, Shogoin, Kawara-machi, Sakyo-ku, Kyoto 606-8507, Japan.
Hosokawa
M
M
Tsukada
H
H
Fukuda
K
K
Nakamura
H
H
Tsukiyama
K
K
Nagashima
K
K
Fujimoto
S
S
Yamada
Y
Y
Seino
Y
Y
D000082:Acetaminophen / Q000493:pharmacokinetics; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001834:Body Water / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology*; D004573:Electrolytes / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005243:Feces; D005746:Gastric Emptying / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D053778:Thiazolidines; D013997:Time Factors
D001786:Blood Glucose; D004573:Electrolytes; D004791:Enzyme Inhibitors; D053778:Thiazolidines; D000082:Acetaminophen; C038131:epalrestat; D013779:Tetrodotoxin; D012236:Rhodanine; D000449:Aldehyde Reductase