Zinc has been reported to exert a gastroprotective action against various experimental gastric lesions suggesting that this
trace element is involved in the integrity of the gastric mucosa. Compounds containing
zinc, such as
polaprezinc, were developed in Japan and used as an antiulcer drugs in the treatment of human
peptic ulcer disease. However, the precise mechanism of Zn(2+) containing compounds and their effects on mucosal integrity, gastroprotection and
ulcer healing remain unclear. We have determined the efficacy of
zinc hydroaspartate, a compound containing Zn(2+), in the mechanism of gastric secretion and
ulcer healing in rats with chronic
gastric ulcers induced by
acetic acid (initial
ulcer area = 28 mm(2)). Rats with
gastric ulcers were randomized into two groups: A) with gastric
fistulas (GF) and B) without gastric
fistulas and received a daily treatment with
zinc hydroaspartate (32-130 mg/kg-d i.g.) for 3, 7 and 14 days. At the termination of each treatment, the area of
gastric ulcers were examined by planimetry, the gastric blood flow (GBF) at
ulcer margin was assessed by
laser Doppler flowmetry and H(2)-gas clearance methods. The venous blood was withdrawn for a measurement of plasma
gastrin levels by radioimmunoassay (RIA). The concentration of Zn(2+) in the gastric juice and mucosa at the
ulcer margin were determined by differential pulse anodic stripping voltammetry (DPASV) and flame atomic absorption spectrometry (FAAS) methods and the gastric biopsy samples were taken for histopathological assessment of the quality of
ulcer healing. The
ulcers healed gradually, with the
ulcer area in the vehicle control rats being diminished by 15%, 48% and 78% upon
ulcer induction at 3, 7 and 14 days, respectively.
Zinc hydroaspartate dose-dependently inhibited the area of
gastric ulcer, the dose reducing this area by 50% (ID(50)) being about 60 mg/kg-d. The mucosal concentration of Zn(2+) significantly was unchanged from the baseline immediately after
ulcer induction (day 0) and at day 3 but then it rose significantly at day 7 after
ulcer induction. Treatment with
zinc hydroaspartate (65 mg/kg-d i.g.), which significantly raised the gastric
luminal and mucosal levels of Zn(2+), significantly accelerated
ulcer healing at day 7 upon
ulcer induction. The GBF, which reached a significantly higher value at the
ulcer margin than the
ulcer bed, was significantly increased in rats treated with
zinc hydroaspartate compared with vehicle-controls. The gastric acid output was significantly inhibited in GF rats with
gastric ulcer at day 3 then restored at day 14 followed by a significant rise in the plasma
gastrin levels. Treatment with
zinc hydroaspartate significantly inhibited gastric secretion and also significantly raised the plasma
gastrin level when compared to vehicle-control rats. We concluded that 1) trace
micronutrients such as Zn(2+) could be successfully measured in the gastric juice and gastric mucosa during
ulcer healing; 2) compounds chelating of Zn(2+) can exert a beneficial influence on the
ulcer healing via Zn(2+) mediated increase in gastric microcirculation, antisecretory activity and
gastrin release, which may enhance the cell proliferation and differentiation during
ulcer healing, ultimately exerting a trophic action on the ulcerated gastric mucosa.