Gastric mucosal damage in experimental diabetes in rats: role of endogenous glutathione.
OBJECTIVE
Spontaneous gastric damage occurs in diabetic rats, but the mechanism is unknown. The aim of this study was to assess the role of glutathione metabolism and gastric mucosal blood flow (GMBF) in the development of such spontaneous gastric damage.


METHODS
Mucosal damage, GMBF, glutathione metabolism, and lipid peroxidation were measured in the stomach of diabetic and control rats.


RESULTS
Spontaneous gastric damage occurred in fasted diabetic rats 4 weeks after streptozotocin administration or pancreatectomy. This was accompanied by a 50% decrement in mucosal content of glutathione; 48 hours after streptozotocin, the decrement of glutathione was only of 25% and no gastric damage was observed. Fed diabetic rats (4 weeks after streptozotocin) had normal glutathione levels and no damage; however, a 30% glutathione depletion achieved by buthionine-sulfoximine administration promoted significant damage. Gastric glutathione synthetic rate, levels of adenosine triphosphate, oxidized glutathione, and malonyldialdehyde were similar in all groups, whereas cysteine concentration was reduced in fasted diabetic animals. Exogenous cysteine attenuated the gastric damage. GMBF was not influenced by diabetes.


CONCLUSIONS
Spontaneous gastric damage in fasted diabetic rats seems to be related to glutathione depletion as a result of limited availability of cysteine and not to increased glutathione oxidation. GMBF changes are not involved.
Goldin
E
E
Gastroenterology Department, Hospital Clinic, University of Barcelona, Spain.
Ardite
E
E
Elizalde
J I
JI
Odriozola
A
A
Panés
J
J
Piqué
J M
JM
Fernández-Checa
J C
JC
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D005753:Gastric Mucosa / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D005978:Glutathione / Q000502:physiology*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D001786:Blood Glucose; D013311:Streptozocin; D005978:Glutathione