We tested the hypothesis that the gastrotoxicity of
ethanol and other damaging agents is influenced through the modulation of
alcohol dehydrogenase (ADH) by using either the ADH-inhibitor
pyrazole or the noninhibitor derivatives of
pyrazole. In time course experiments, the protection by both compounds was evident up to 48 hr before
ethanol administration. Both drugs were also protected, from about 24 hr, from gastric mucosal damage induced by
aspirin and
hydrochloric acid. In order to examine the role of endogenous
prostaglandins and sulfhydryls in this protection,
indomethacin and
N-ethylmaleimide were used, of which only the sulfhydryl
alkylator antagonized (by about 50%) the protection by
pyrazole and
3-methylpyrazole. Studies with
monastral blue B revealed the protective role of both
pyrazole and
3-methylpyrazole against early
vascular injury in the gastric mucosa. We conclude that because both the ADH-inhibitor
pyrazole and the noninhibitor derivatives of
pyrazole exert gastro-protection, and because both compounds protect against
aspirin and HCI, ADH inhibition is not involved in this protection. We also suggest that although
prostaglandins appear to have minimal involvement in the mechanism of protection, endogenous sulfhydryls may be important mediators. Furthermore, the functional and structural mechanism of this protection seems to be the prevention of acute
vascular injury.