lithium-chloride and Gastritis

While the incidence of duodenal ulcer disease has been documented to be greater in men than in women, this observation has not been previously noted in animal studies of the upper gastrointestinal tract. In this study, we questioned whether the cytoprotective properties of 16, 16-dimethyl PGE2 were sex-related by comparing the degree of ethanol-induced hemorrhagic gastritis in male and female rats pretreated with 16,16-dimethyl PGE2 or lithium chloride. Animals receiving 16,16-dimethyl PGE2 or lithium chloride had significantly less ethanol-induced hemorrhagic gastritis (1.17 +/- 0.15 and 1.24 +/- 0.13, respectively, p less than 0.001) when compared with controls (2.69 +/- 0.10). Female rats treated with 16,16-dimethyl PGE2 had 59% less hemorrhagic gastritis than male rats treated similarly (0.76 +/- 0.14 vs 1.86 +/- 0.19 respectively, p less than 0.001). This sex-related difference in hemorrhagic gastritis was not noted in male and female rats receiving lithium chloride (1.24 +/- 0.15 vs 1.23 +/- 0.27, respectively). However, female rats treated with 16, 16-dimethyl PGE2 had significantly less hemorrhagic gastritis when compared with female rats receiving lithium chloride (0.76 +/- 0.14 vs 1.24 +/- 0.15 respectively, p less than 0.05).

Topics: 16,16-Dimethylprostaglandin E2; Animals; Chlorides; Ethanol; Female; Gastric Mucosa; Gastritis; Gastrointestinal Hemorrhage; Lithium; Lithium Chloride; Male; Peptic Ulcer; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Sex Factors

Lithium chloride was evaluated as a potential protective agent against ethanol-induced hemorrhagic gastritis in rats. Rats received lithium chloride intragastrically (30, 60, or 90 mg/kg i.g.) or subcutaneously (3, 5, 10, 15, 20, 30, 60, or 90 mg/kg s.c.), or a placebo (H2O i.g. or 0.9% NaCl s.c.). Ninety minutes later 1 cm3 of 95% ethanol was administered intragastrically. After 30 min, the rats were killed and their stomachs were removed and visually scored for gross hemorrhagic gastritis. Lithium chloride at all doses less than 3 mg/kg significantly improved hemorrhagic gastritis when compared with the placebo. Moreover, rats treated with lithium chloride intragastrically had significantly less hemorrhagic gastritis than those treated subcutaneously even though serum lithium levels were similar. To determine if lithium's protective properties related to acid inhibition, pylorus-ligated and gastric fistula rats were studied. The median effective dose for lithium chloride was 20-30 mg/kg and the nonantisecretory dose was 3 mg/kg. No difference in hemorrhagic gastritis was noted between controls and animals receiving the nonantisecretory dose. However, at higher doses (LiCl 30, 60, and 90 mg/kg), lithium's protective properties persisted in spite of adding 150 mM HCl to the intragastrically administered ethanol (p less than 0.001). To determine further if lithium chloride stimulated endogenous prostaglandins, indomethacin, a prostaglandin inhibitor, was administered. Indomethacin did not alter lithium chloride's protective properties. In fact, when compared with exogenously administered 16,16-dimethyl prostaglandin E2 (5 and 500 micrograms/kg), high-dose LiCl (30, 60, or 90 mg/kg) resulted in significantly more protection against ethanol-induced injury (p less than 0.001). In contrast, when both nonantisecretory doses were compared, 16,16-dimethyl prostaglandin E2 (5 micrograms/kg) gave significantly better protection than LiCl (3 mg/kg). These data indicate that LiCl is a potent gastric antisecretory and protective agent. The protective properties of LiCl appear to be related to acid inhibition and be independent of endogenous prostaglandins, although other protective mechanisms may be present at higher LiCl doses. Additionally, this study indicates that LiCl may have clinical application in protecting the gastric mucosa against hemorrhagic gastritis.

Topics: Animals; Chlorides; Dinoprostone; Disease Models, Animal; Drug Evaluation; Ethanol; Gastric Acid; Gastric Mucosa; Gastritis; Gastrointestinal Hemorrhage; Indomethacin; Lithium; Lithium Chloride; Prostaglandins E; Rats; Rats, Inbred Strains