Mechanism of diethyldithiocarbamate-induced gastric ulcer formation in the rat.
Diethyldithiocarbamate (DDC) was injected subcutaneously in the rat and the mechanism of gastric ulcer formation was investigated. DDC induced gastric ulcers in a dose-dependent manner. DDC significantly suppressed gastric mucosal copper-zinc superoxide dismutase (Cu, Zn-SOD) activity at 2 hr. However, manganese-superoxide dismutase (Mn-SOD) activity was not changed. Gastric mucosal blood flow (GMBF) decreased to 52% of the control level at 2 hr after administration of DDC and gradually increased to reach the control level by 7 hr. A Shay rat preparation (4 hr) was used to study gastric secretion. DDC (200, 400 and 800 mg/kg) inhibited acid secretion to about 80% of the control level. Histopathological examination of the gastric mucosa after administration of DDC revealed mucosal congestive findings from 1 hr to 3 hr. These data suggested that the mechanism of DDC-induced gastric ulcer formation may be attributable to a decreased level of GMBF and O2- production owing to decreased SOD activity.
Ogino
K
K
Department of Public Health, Yamaguchi University School of Medicine, Ube, Japan.
Hobara
T
T
Kawamoto
T
T
Kobayashi
H
H
Iwamoto
S
S
Oka
S
S
Okazaki
Y
Y
D000818:Animals; D004050:Ditiocarb / Q000633:toxicity*; D005744:Gastric Acid / Q000378:metabolism; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism
D004050:Ditiocarb; D013482:Superoxide Dismutase