Lipopolysaccharide treatment induces adaptive cytoprotection in the portal hypertensive gastric mucosa of rats
Malba E. A. Tavares, Jose Luiz A. Barros, Thiago E. V. Lemos,Gerson J. N. Ferraz, Jose Murilo R. Zeitune, Jose Geraldo P. Ferraz, Paula R. S. Camara.
Objective: Upper gastrointestinal bleeding in patients with cirrhosis and portal hypertension is a frequent complication that potentially modifies the survival of these patients. This phenomenon may occur due to excessive endotoxin translocation, leading to system debugging liver overload, and systemic endotoxemia, with excessive production of mediators by immune cells. The presence of these inflammatory mediators may increase the susceptibility of gastric mucosa to lesions induced by various damaging agents. As such, this study aimed to determine the resistance of portal hypertensive gastric mucosa to endotoxin and ethanol stimulation.
Methods: Portal hypertension was induced in rats by bile duct ligation or portal vein stenosis (PVS) while controls underwent a sham operation. The effect of endotoxin on the gastric mucosa was evaluated by acute or chronic LPS treatment. Ethanol-induced damage was assessed using ex vivo gastric chamber experiments. Gastric blood flow was measured by laser Doppler flowmetry.
Results: Acute LPS treatment intensified the ethanol-induced gastric damage in the healthy (control) group in a dose-dependent manner (0.3-3 mg/kg). In contrast, the gastric mucosa of the PVS group presented tolerance after a single dose of LPS (3 mg/kg). Chronic LPS treatment (1 mg/kg) significantly reduced the gastric mucosal lesion area in both the PVS and control groups. Additionally, the cirrhotic animals were found not to survive the minimum dose of LPS.
Conclusion: Our results suggest that chronic LPS treatment induces adaptative cytoprotection to ethanol-induced injury in the gastric mucosa of PVS and healthy rats; however, acute LPS treatment increases mortality in cirrhotic rats.
Key words: Adaptive cytoprotection; Gastric mucosa; Lipopolysaccharide; Portal hypertension