Protein and non-protein sulfhydryls and disulfides in gastric mucosa and liver after gastrotoxic chemicals and sucralfate: possible new targets of pharmacologic agents.
OBJECTIVE
To investigate the role of major non-protein and protein sulfhydryls and disulfides in chemically induced gastric hemorrhagic mucosal lesions (HML) and the mechanism of gastroprotective effect of sucralfate.


METHODS
Rats were given 1 mL of 75% ethanol, 25% NaCl, 0.6 mol/L HCl, 0.2 mol/L NaOH or 1% ammonia solutions intragastrically (i.g.) and sacrificed 1, 3, 6 or 12 min later. Total (reduced and oxidized) glutathione (GSH + GSSG), glutathione disulfide (GSSG), protein free sulfhydryls (PSH), protein-glutathione mixed disulfides (PSSG) and protein cystine disulfides (PSSP) were measured in gastric mucosa and liver.


RESULTS
Reduced glutathione (GSH) was depleted in the gastric mucosa after ethanol, HCl or NaCl exposure, while oxidized glutathione (GSSG) concentrations increased, except by HCl and NaOH exposure. Decreased levels of PSH after exposure to ethanol were observed, NaCl or NaOH while the total protein disulfides were increased. Ratios of reduced to oxidized glutathione or sulfhydrils to disulfides were decreased by all chemicals. No changes in thiol homeostasis were detected in the liver after i.g. abbreviation should be spelled out the first time here administration of ethanol. Sucralfate increased the concentrations of GSH and PSH and prevented the ethanol-induced changes in gastric mucosal thiol concentrations.


CONCLUSIONS
Our modified methods are now suitable for direct measurements of major protein and non-protein thiols/disulfides in the gastric mucosa or liver. A common element in the pathogenesis of chemically induced HML and in the mechanism of gastroprotective drugs seems to be the decreased ratios of reduced and oxidized glutathione as well as protein sulfhydryls and disulfides.
Nagy
Lajos
L
Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nagata
Miki
M
Szabo
Sandor
S
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use; D004220:Disulfides / Q000378:metabolism*; D000431:Ethanol; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006471:Gastrointestinal Hemorrhage; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006851:Hydrochloric Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D012972:Sodium Hydroxide; D013272:Stomach Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D013392:Sucralfate / Q000494:pharmacology / Q000627:therapeutic use*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D000897:Anti-Ulcer Agents; D004220:Disulfides; D013438:Sulfhydryl Compounds; D000431:Ethanol; D012965:Sodium Chloride; D013392:Sucralfate; D012972:Sodium Hydroxide; D005978:Glutathione; D006851:Hydrochloric Acid; D019803:Glutathione Disulfide