Preventive effect of rebamipide on N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats

Exp Toxicol Pathol. 2015 Mar;67(3):271-7. doi: 10.1016/j.etp.2015.01.003. Epub 2015 Jan 20.

Abstract

Chemoprevention strategies against gastric cancer (GC) need to be explored in light of the fact that stomach cancer still occurs in the absence of Helicobacter pylori (HP) infection and following HP eradication. We evaluated the effect of rebamipide on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced carcinogenesis in SD rats. Thirty-nine male rats were divided into four groups based on whether or not they were treated with rebamipide and/or MNNG: Control, Rebamipide, Control-M, and Rebamipide-M groups. From 8 weeks of age, rats in the Control-M and Rebamipide-M groups received MNNG in drinking water for 30 weeks. The Rebamipide and Rebamipide-M groups were administered 5mg/kg/day of rebamipide. At 50 weeks, cancerous lesions were not observed in either the Control or Rebamipide groups. Nine rats in the Control-M group had developed GC, while four rats in the Rebamipide-M group had developed GC. The incidence of cancer in the Rebamipide-M group was significantly less than in the Control-M group (p<0.05), with a trend toward a lower incidence of invasive carcinoma in the Rebamipide-M group. Carcinomatous invasion into the muscularis propria was not observed in the Rebamipide-M group. In conclusion, the present study demonstrates that rebamipide suppresses. MNNG-induced carcinogenesis and may also inhibit progression of cancer in rats.

Keywords: Chemoprevention; Gastric cancer; N-methyl-N′-nitro-N-nitrosoguanidine; Rat; Rebamipide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology*
  • Adenocarcinoma / prevention & control
  • Alanine / analogs & derivatives*
  • Alanine / pharmacology
  • Animals
  • Antioxidants / pharmacology*
  • Carcinogenesis / drug effects*
  • Carcinogens / toxicity
  • Disease Models, Animal
  • Immunohistochemistry
  • Male
  • Methylnitronitrosoguanidine / toxicity
  • Quinolones / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / prevention & control

Substances

  • Antioxidants
  • Carcinogens
  • Quinolones
  • Methylnitronitrosoguanidine
  • rebamipide
  • Alanine