TY - JOUR
T1 - The correlation of the weakening effect on gastric mucosal integrity by 5-HT with neutrophil activation
AU - Ko, Joshua K.S.
AU - Ma, Jun-Jiang
AU - Chow, Jimmy Y. C.
AU - Ma, Li
AU - Cho, Chi-Hin
N1 - Funding Information:
This study was supported in part by the CRCG and RGC grants from the University of Hong Kong and the Hong Kong Research Grant Council, respectively.
PY - 1998/4
Y1 - 1998/4
N2 - The effects of 5-hydroxytryptamine (5-HT) on ethanol-induced gastric mucosal damage and on epithelial and vascular integrity were investigated. Male Sprague-Dawley rats were administered with 5-HT (5 or 10 mg/kg, IP) 30 min prior to the challenge with ethanol (40% v/v, 10 ml/kg, PO). 5-HT dose dependently aggravated ethanol-induced injury in the gastric mucosa. Both xanthine oxidase (XO) and myeloperoxidase (MPO) activities in the mucosa were significantly increased with the high dose of 5-HT, which also potentiated the elevation of these enzyme activities by ethanol. However, the mucosal superoxide dismutase activity was left unaltered. In neutropenic (antineutrophil serum-treated) animals, the ethanol-induced gastric mucosal injury was significantly ameliorated, with or without the pretreatment of 5- HT (10 mg/kg). In addition, the effect of 5-HT on the activity of MPO, but not of XO, was also attenuated in these animals. In the ex vivo gastric chamber study on pentobarbital-anesthetized animals, volume of gastric secretion was significantly decreased in the 5-HT-treated groups, with further reduction after ethanol incubation. Transmucosal potential difference (PD) was significantly reduced in 5-HT-treated rats, which also potentiated the ethanol-induced drop in PD. Nevertheless, 5-HT dose dependently increased mucosal vascular permeability and further enhanced during ethanol incubation. These findings suggest that 5-HT adversely affects the defense mechanisms of the gastric mucosa by reducing the secretory function of the mucosal cells and to weaken the epithelial and vascular integrity. Neutrophil activation appears to be responsible for the detrimental effects of 5-HT partly through the elevation in MPO activity. The increase in mucosal XO activity by 5-HT may induce free radical production and possibly modulate the ulcerogenic processes.
AB - The effects of 5-hydroxytryptamine (5-HT) on ethanol-induced gastric mucosal damage and on epithelial and vascular integrity were investigated. Male Sprague-Dawley rats were administered with 5-HT (5 or 10 mg/kg, IP) 30 min prior to the challenge with ethanol (40% v/v, 10 ml/kg, PO). 5-HT dose dependently aggravated ethanol-induced injury in the gastric mucosa. Both xanthine oxidase (XO) and myeloperoxidase (MPO) activities in the mucosa were significantly increased with the high dose of 5-HT, which also potentiated the elevation of these enzyme activities by ethanol. However, the mucosal superoxide dismutase activity was left unaltered. In neutropenic (antineutrophil serum-treated) animals, the ethanol-induced gastric mucosal injury was significantly ameliorated, with or without the pretreatment of 5- HT (10 mg/kg). In addition, the effect of 5-HT on the activity of MPO, but not of XO, was also attenuated in these animals. In the ex vivo gastric chamber study on pentobarbital-anesthetized animals, volume of gastric secretion was significantly decreased in the 5-HT-treated groups, with further reduction after ethanol incubation. Transmucosal potential difference (PD) was significantly reduced in 5-HT-treated rats, which also potentiated the ethanol-induced drop in PD. Nevertheless, 5-HT dose dependently increased mucosal vascular permeability and further enhanced during ethanol incubation. These findings suggest that 5-HT adversely affects the defense mechanisms of the gastric mucosa by reducing the secretory function of the mucosal cells and to weaken the epithelial and vascular integrity. Neutrophil activation appears to be responsible for the detrimental effects of 5-HT partly through the elevation in MPO activity. The increase in mucosal XO activity by 5-HT may induce free radical production and possibly modulate the ulcerogenic processes.
KW - 5-HT
KW - Ethanol
KW - Free radicals
KW - Neutrophil
KW - Gastric mucosal integrity
UR - http://www.scopus.com/inward/record.url?scp=0032054804&partnerID=8YFLogxK
U2 - 10.1016/S0891-5849(97)00428-0
DO - 10.1016/S0891-5849(97)00428-0
M3 - Journal article
C2 - 9607612
AN - SCOPUS:0032054804
SN - 0891-5849
VL - 24
SP - 1007
EP - 1014
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 6
ER -