TY - JOUR
T1 - Involvement of the xanthine-xanthine oxidase system and neutrophils in the development of acute gastric mucosal lesions in rats with water immersion restraint stress
AU - Nishida, Keiji
AU - Ohta, Yoshiji
AU - Kobayashi, Takashi
AU - Ishiguro, Isao
PY - 1997/1/1
Y1 - 1997/1/1
N2 - In rats subjected to water immersion restraint (WIR) stress for 1, 3, and 6 h, gastric mucosal lesions developed time-dependently with an increase in lipid peroxide (LPO) levels and a decrease in nonprotein sulfhydryl levels in the gastric mucosa. The gastric mucosal xanthine oxidase (XO) activity significantly increased with the conversion of xanthine dehydrogenase (XD) to XO at 6 h of WIR (3.2-fold that of the control group without WIR). A significant increase in myeloperoxidase (MPO) activity, an index of neutrophil infiltration, occurred in the gastric mucosa at 3 and 6 h of the WIR (2.2- and 3.3-fold that of the control group without WIR, respectively). In contrast, superoxide dismutase, catalase, and glutathione peroxidase activities in the gastric mucosa did not change during the WIR period. Pretreatment with either allopurinol (AP), an inhibitor of XO, or soybean trypsin inhibitor (STI), a serine protease inhibitor, attenuated the lesion development at 6 h of WIR, but not at 3 h. In the gastric mucosa of rats pretreated with AP, enhancements of LPO formation, sulfhydryl oxidation, and XO activity found at 6 h of WIR were prevented with inhibition of XD plus XO activity, while in the gastric mucosa of rats pretreated with STI, these enhancements were prevented with inhibition of the conversion of XD to XO. In the gastric mucosa of rats pretreated with anti-polymorphonuclear leukocyte antiserum, the lesion development and enhanced LPO formation and sulfhydryl oxidation found at 3 and 6 h of WIR were prevented with a decrease in increased MPO activity. These results indicate that in the gastric mucosa of rats with WIR stress, the progression of lesions is mainly related to enhanced LPO formation and sulfhydryl oxidation which depend on an increased generation of oxygen free radicals via the xanthine-XO system and neutrophils rather than the change in the oxygen free radical-scavenging activity of antioxidant enzymes. The present results also suggest that increased gastric mucosal LPO formation and sulfhydryl oxidation found at 3 h of WIR could be mainly due to neutrophil-derived oxygen free radicals, while enhanced gastric mucosal LPO formation and sulfhydryl oxidation found at 6 h of WIR could be due to both neutrophil- and XO-derived oxygen free radicals.
AB - In rats subjected to water immersion restraint (WIR) stress for 1, 3, and 6 h, gastric mucosal lesions developed time-dependently with an increase in lipid peroxide (LPO) levels and a decrease in nonprotein sulfhydryl levels in the gastric mucosa. The gastric mucosal xanthine oxidase (XO) activity significantly increased with the conversion of xanthine dehydrogenase (XD) to XO at 6 h of WIR (3.2-fold that of the control group without WIR). A significant increase in myeloperoxidase (MPO) activity, an index of neutrophil infiltration, occurred in the gastric mucosa at 3 and 6 h of the WIR (2.2- and 3.3-fold that of the control group without WIR, respectively). In contrast, superoxide dismutase, catalase, and glutathione peroxidase activities in the gastric mucosa did not change during the WIR period. Pretreatment with either allopurinol (AP), an inhibitor of XO, or soybean trypsin inhibitor (STI), a serine protease inhibitor, attenuated the lesion development at 6 h of WIR, but not at 3 h. In the gastric mucosa of rats pretreated with AP, enhancements of LPO formation, sulfhydryl oxidation, and XO activity found at 6 h of WIR were prevented with inhibition of XD plus XO activity, while in the gastric mucosa of rats pretreated with STI, these enhancements were prevented with inhibition of the conversion of XD to XO. In the gastric mucosa of rats pretreated with anti-polymorphonuclear leukocyte antiserum, the lesion development and enhanced LPO formation and sulfhydryl oxidation found at 3 and 6 h of WIR were prevented with a decrease in increased MPO activity. These results indicate that in the gastric mucosa of rats with WIR stress, the progression of lesions is mainly related to enhanced LPO formation and sulfhydryl oxidation which depend on an increased generation of oxygen free radicals via the xanthine-XO system and neutrophils rather than the change in the oxygen free radical-scavenging activity of antioxidant enzymes. The present results also suggest that increased gastric mucosal LPO formation and sulfhydryl oxidation found at 3 h of WIR could be mainly due to neutrophil-derived oxygen free radicals, while enhanced gastric mucosal LPO formation and sulfhydryl oxidation found at 6 h of WIR could be due to both neutrophil- and XO-derived oxygen free radicals.
KW - Gastric mucosal lesion
KW - Lipid peroxidation
KW - Myeloperoxidase
KW - Neutrophil
KW - Oxygen radicals
KW - Water immersion restraint stress
KW - Xanthine oxidase
UR - http://www.scopus.com/inward/record.url?scp=0030768072&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030768072&partnerID=8YFLogxK
U2 - 10.1159/000201464
DO - 10.1159/000201464
M3 - Article
C2 - 9324161
AN - SCOPUS:0030768072
SN - 0012-2823
VL - 58
SP - 340
EP - 351
JO - Digestion
JF - Digestion
IS - 4
ER -