Role of acid back-diffusion, glutathione, oxyradical, and histamine in antral hemorrhagic ulcer in rats: the protective effect of lysozyme chloride and antioxidants.
The pathogenesis of gastric antral hemorrhage and ulceration is unclear. This paper first proposes that antral hemorrhagic ulcers produced in rats are associated with attenuation of defensive parameters (such as mucosal glutathione levels and histamine release, as well as aggravation of aggressive factors) including gastric acid back-diffusion and oxyradical generation. The protective effects of lysozyme chloride and antioxidants on this ulcer model were also evaluated. After being deprived of food for 24 hours followed by refeeding for 1 hour, rats were injected with 1.0 mol HCl/L intragastrically under potent analgesia of diethylether-anesthesia to induce antral ulcer. Control rats received a normal saline solution only. Rats were then given free access to water and food for 4 days. Before the experiment began, rats were again deprived of food for 24 hours. Following anesthetization, their stomachs were irrigated for 3 hours with either normal saline or a physiological acid solution containing 100 mmol HCl/L and 54 mmol NaCl/L. Aggravation of various aggressive and defensive parameters in antral mucosa was observed in refed rats that had received 1.0 mol HCl/L. A high relationship of mucosal glutathione level (r = -0.8754, P <.05) or lipid peroxides generation (r = 0.8198) to antral ulceration was obtained in those ulcerated rats. Intragastric lysozyme chloride (50-200 mg/kg) injected three times daily produced a dose-dependent attenuation of various gastric parameters in the acid-irrigated stomachs of antral ulcer rats. Intraperitoneal injections of various antioxidants, including exogenous glutathione, allopurinol, or dimethylsulfoxide also attenuated antral ulcer. In conclusion, the imbalance of aggressive factors, such as acid back-diffusion and oxyradicals-as well as defensive factors including glutathione and histamine-is important in modulating antral hemorrhagic ulcers that can be ameliorated by lysozyme chloride or antioxidants in rats.
Hung
Chen-Road
CR
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan. crchung@mail.ncku.edu.tw
Wang
Paulus S
PS
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D004058:Diffusion; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000473:pathology; D005978:Glutathione / Q000378:metabolism* / Q000627:therapeutic use; D006632:Histamine / Q000378:metabolism; D006851:Hydrochloric Acid / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009113:Muramidase / Q000627:therapeutic use*; D011706:Pyloric Antrum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D000975:Antioxidants; D008054:Lipid Peroxides; D006632:Histamine; D009113:Muramidase; D005978:Glutathione; D006851:Hydrochloric Acid