Effect of long-term acid gastric inhibition on bacterial translocation in cirrhotic rats

Eur J Gastroenterol Hepatol. 2015 May;27(5):570-6. doi: 10.1097/MEG.0000000000000319.

Abstract

Background: Bacterial translocation (BT) related to intestinal bacterial overgrowth (IBO) plays an important role in the pathogenesis of bacterial infections in cirrhosis. Inhibition of acid gastric secretion promotes IBO and might favor BT. We evaluated the effect of long-term inhibition of acid gastric secretion on BT in cirrhotic rats.

Methods: Cirrhotic rats with and without ascites induced by oral CCl4 and controls were randomized to treatment with a daily subcutaneous injection of placebo, ranitidine (50 mg/kg), or pantoprazole (8 mg/kg) during 2 weeks. Continuous pH-metry was performed for 2 h before and at the end of treatment; thereafter, a laparotomy to obtain samples of blood, mesenteric lymph nodes, ascites, spleen, liver, and cecal stools was performed.

Results: Ranitidine and pantoprazole increased gastric pH as compared with placebo (P<0.001). However, antisecretory drugs increased the incidence of BT only in ascitic rats treated with ranitidine (P<0.05) or pantoprazole (P=0.07) when compared with placebo-treated ascitic rats or cirrhotic rats without ascites treated with the same drug. Cirrhotic ascitic rats treated with pantoprazole showed a trend toward an increased incidence of IBO (P=0.08), a higher ileal malondialdehyde level (P<0.01), and an increased production of tumor necrosis factor-α (P<0.05).

Conclusion: Although inhibition of acid gastric secretion increased gastric pH in all animals, the incidence of BT increased only in ascitic rats, and it was associated with a trend toward an increase in IBO incidence, a higher ileal malondialdehyde level, and an increased production of serum tumor necrosis factor-α. Therefore, antisecretory drugs should be carefully administered to cirrhotic ascitic patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / pharmacology
  • Animals
  • Anti-Ulcer Agents / pharmacology*
  • Ascites / etiology
  • Bacterial Translocation / drug effects*
  • Blind Loop Syndrome / chemically induced
  • Blind Loop Syndrome / microbiology*
  • Gastric Acid / chemistry
  • Gastric Acid / metabolism*
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / metabolism
  • Gastrointestinal Microbiome / drug effects
  • Hydrogen-Ion Concentration / drug effects
  • Ileum / chemistry
  • Intestinal Mucosa / chemistry
  • Intestinal Mucosa / drug effects
  • Liver Cirrhosis, Experimental / blood
  • Liver Cirrhosis, Experimental / complications*
  • Male
  • Malondialdehyde / analysis
  • Pantoprazole
  • Ranitidine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tumor Necrosis Factor-alpha / blood

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Ranitidine
  • Pantoprazole