Role of nitric oxide in the gastro-protective effect of lithium.
OBJECTIVE
Lithium is widely used for the management of neuropsychiatric symptoms in bipolar disorders. A few studies have shown that lithium has a protective effect against gastric damage with an unknown mechanism. Some of the actions of lithium are mediated through nitric oxide (NO), which has an important role in the regulation of gastric wall blood flow as well as gastric mucosal integrity. The aim of this study was to test the hypothesis if the gastro-protective effect of lithium is mediated through NO.


METHODS
Male Wistar rats were pre-treated with either a non-selective NO synthase inhibitor (N(G)-nitro-l-arginine, 10mg/kg), a selective inducible NO synthase inhibitor (aminoguanidine, 100mg/kg) or saline. Lithium carbonate (10, 20, 50 and 100mg/kg) was then administered intraperitoneally 1h before the induction of gastric mucosal damage. Gastric damage was induced by either water immersion stress or ethanol gavage in rats.


RESULTS
Lithium had a significant protective effect in both stress and ethanol-induced gastric damage, but it needed in ethanol-induced gastric damage a higher dose than in the stress induced lesion. Lithium carbonate doses 20 and 50mg/kg produced plasma concentrations that were in the range of human therapeutic Li levels (0.6-1.0muM). Pre-treatment of animals with N(G)-nitro-l-arginine (20 and 40mg/kg) reduced the protective effect of lithium against ethanol-induced gastric damage, but not in stress-induced damage. Aminoguanidine administration showed no effect on the damage reduction either in control or lithium treated rats.


CONCLUSIONS
The results indicate that NO might play a role in the gastro-protective effect of lithium against ethanol-induced gastric damage in rats.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Firouzeh
F
Nejadkey
Arezo
A
Nahavandi
Ahmad R
AR
Dehpour
Ali R
AR
Mani