Protective action of oral N-acetylcysteine against gastric injury: role of hypertonic sodium.
N-acetylcysteine (NAC), when administered orally as a 20% solution, is a potent protective agent against gastric injury in the rat stomach induced by absolute ethanol. The present study was undertaken to define the means by which this protection is mediated. The notion that NAC acts as a glutathione precursor was excluded when N-acetylserine (NAS) was noted to be equally protective against alcohol injury. The NAS molecule contains a hydroxyl moiety at the site where NAC contains a sulfhydryl. To orally administer 20% NAC at a neutral pH, NaOH is added to the free acid form to keep NAC in solution. We determined by titration that a sodium concentration of 1.2 M results. Thus it became apparent that the protective effect of NAC might be mediated through the sodium employed to titrate NAC. Accordingly, we examined various sodium salts and assessed their relative protective effects against alcohol injury. Both sodium acetate and sodium chloride in 1 M solutions were found to be equally effective in preventing alcohol injury with the same efficiency as 1 M sodium solutions of NAC and NAS, excluding the acetate portion of NAC and NAS as being of primary importance for protection to occur. Further study, using different concentrations of sodium chloride (i.e., 150-1,000 mM) revealed that the 1 M solution was most optimal in preventing alcohol injury. One molar sodium by itself and when administered as part of the NAC solution also prevented gastric injury by concentrated acid and base.(ABSTRACT TRUNCATED AT 250 WORDS)
Barreto
J C
JC
Department of Surgery, University of Texas Medical School, Houston 77030.
Smith
G S
GS
Tornwall
M S
MS
Miller
T A
TA
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D006982:Hypertonic Solutions; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D012964:Sodium / Q000502:physiology*; D013272:Stomach Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013276:Stomach Ulcer / Q000517:prevention & control
D006982:Hypertonic Solutions; D012694:Serine; D012964:Sodium; C012162:N-acetylserine; D000111:Acetylcysteine