Gastric mucosal damage induced by arecoline seizure in rats.
In an attempt to know the relation of seizure and gastric mucosal damage, we challenged arecoline (ACL) centrally to induce seizure and investigated gastric hemorrhagic injury in acid-irrigated stomachs of rats. The protective effects of several drugs also were evaluated. After deprivation of food for 24 h, rats were received laparotomy under diethylether-anesthesia. Both pylorus sphincters and carotid esophagus were ligated. The forestomach was equipped with a cannula for gastric irrigation. After recovery from anesthesia (approximately 1 h), the stomach was irrigated for 2 h with an acid solution containing 100 mM HCl and 54 mM NaCl or the same volume of normal saline. Intracerebroventricular (i.c.v.) ACL (0, 1, 3 or 10 mg/kg dissolved in 10 microl of CSF) was challenged to rats immediately after gastric irrigation. The seizure in rats was produced by ACL in a dose-related manner. The ulcerogenic parameters such as decrease of gastric mucosal glutathione levels and increase of histamine concentrations and lipid peroxide generations as well as the raise of luminal hemoglobin contents and exacerbated mucosal lesions were obtained depending on the doses of ACL challenged. These ulcerogenic parameters produced in ACL (10 mg/kg, i.c.v.) seizure rats were markedly ameliorated by gastric vagotomy or central anticholinergics. Intraperitoneal ketotifen, zinc sulfate, diphenhydramine or cimetidine also produced significant (p<0.05) inhibitions of these ulcerogenic parameters in ACL seizure rats. In conclusion, central ACL seizure may produce gastric oxidative stress and hemorrhagic lesions via vagal nervous activation and histamine release in acid-irrigated stomachs of rats.
Hung
C R
CR
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. crhung@mail.ncku.edu.tw
Cheng
J T
JT
Shih
C S
CS
D000818:Animals; D001115:Arecoline / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005751:Gastric Lavage; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005766:Gastrointestinal Contents / Q000737:chemistry; D005978:Glutathione / Q000378:metabolism; D006454:Hemoglobins / Q000032:analysis; D006632:Histamine / Q000378:metabolism; D007276:Injections, Intraventricular; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced*; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D006454:Hemoglobins; D008054:Lipid Peroxides; D001115:Arecoline; D006632:Histamine; D005978:Glutathione