Orally administered L-arginine and glycine are highly effective against acid reflux esophagitis in rats.
BACKGROUND
Reflux esophagitis is caused mainly by excessive exposure of the mucosa to gastric contents. In the present study, we examined the effect of several amino acids on acid reflux esophagitis in rats.


METHODS
After 18 h of fasting, acid reflux esophagitis was induced by ligating both the pylorus and the transitional region between the forestomach and the corpus under ether anesthesia, and the animals were killed 4 h later. The severity of esophagitis was reduced by the oral administration of omeprazole, a proton pump inhibitor, or pepstatin, a specific pepsin inhibitor.


RESULTS
The development of esophageal lesions was dose-dependently prevented by L-arginine and glycine, given intragastrically (i.g.) after the ligation, with complete inhibition obtained at 250 mg/kg and 750 mg/kg, respectively, and these effects were not influenced by the prior s.c. administration of indomethacin or L-NAME. By contrast, both L-alanine and L-glutamine given i.g. after the ligation aggravated these lesions in a dose-dependent manner. These amino acids had no effect on acid secretion but increased the pH of the gastric contents to 1.8~2.3 due to their buffering action.


CONCLUSIONS
The results confirmed an essential role for acid and pepsin in the pathogenesis of acid reflux esophagitis in the rat model and further suggested that various amino acids affect the severity of esophagitis in different ways, due to yet unidentified mechanisms; L-alanine and L-glutamine exert a deleterious effect on the esophagitis, while L-arginine and glycine are highly protective, independent of endogenous prostaglandins and nitric oxide.
Department of Pharmacology and Experimental Therapeutics, Division of Pathological Sciences, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan.
Kenji
K
Nagahama
Hikaru
H
Nishio
Masanori
M
Yamato
Koji
K
Takeuchi
D000284:Administration, Oral; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004942:Esophagitis, Peptic / Q000517:prevention & control*; D005766:Gastrointestinal Contents / Q000737:chemistry; D005998:Glycine / Q000008:administration & dosage / Q000627:therapeutic use*; D006863:Hydrogen-Ion Concentration; D051381:Rats
D001120:Arginine; D005998:Glycine