EFFECT OF ALKALINE IONIZED WATER ON GASTRIC MUCOSAL INJURY INDUCED BY ASPIRIN IN RATS
by Yuji Naito Toshikazu Yoshikawa, Tomohisa Takagi, Tsuyoshi
Ishikawa, Osamu Handa, Naoyuki Matsumoto, Kiichi Matsuyama, Nobuaki Yagi,
Norimasa Yoshida, Motoharu Kondo (Kyoto Prefectural University of Medicine,
First Dept. of Internal Medicine)
Summary
One of the objectives of this study is to determine effects of alkaline
ionized water (AIW) on acute gastric mucosal injury induced by aspirin in
rats. Oral doses of acidified aspirin (200 mg/kg) resulted in linear hemorrhagic
erosion and increase in myeloperoxidase (MPO) activity, an index of neutrophil
infiltration, in gastric mucosa. These instances of increase in total erosion
and MPO activity were inhibited by administration of AIW (pH 10.5, ORP 450mV)
for two weeks. Aspirin administration resulted in early increase in values
of tumor necrosis factor (TNF a /cinc2 ~ ) plasma and tissue levels. The
increase in TNF a /cinc2 ~ was also inhibited by administration of ArW.
These results indicate that chronic administration of AIW is effective against
aspirin induced gastric mucosal injury, and that its cyto protective action
is associated with inhibition of neutrophil accumulation on gastric mucosa
or with decline of inflammatory cytokine production.
Purpose of tests
Hopeful examples of cliffical application of alkaline ionized water to gastrointestinal
disorders are as follows;
1) Non ulcer dyspepsia (NUD) (at epigastria)
2) Irritable bowel syndrome (IBS)
3) Constipation caused by constitutional disorders (ex. diabetes, hypothyroid
syndrome).
4) Peptic ulcer disease
5) Habitual users of non steroid anti inflammatory drug (NSIAD).
As to 1) and 20 above, clinical tests have already been conducted. We have
been studying mechanism of gastric mucosal injury in detail, and reported
the meaning of inflammatory reactions and the role of active oxygen and
lipid hyperoxidation in its process. Also for this symposium, we have examined
effects of alkaline ionized water by testing experimental models of gastric
mucosal injury using rats as well as cultured gastric mucosal tissues. As
a result, we have found the following;
1) Alkaline ionized water does not act directly to offset active oxygen.
2) Cyto protective action on gastric mucosa is not recognized in the tests
with short term dose of A1W
3) According to the tests on rats that were given A1W for 2 weeks, experimental
gastric mucosal injury was found to be significantly inhibited.
Gastric mucosal injury models we studied include those induced by ischemia
reperfusion, aspirin and stress. Nonsteroid antiinflammatory drug (NSAID)
is one of the most commonly used drugs in clinical treatment these days
due to its wide range of pharmacological functions. However, its side effect,
gastric mucosal injury is becoming a problem. It is believed that the main
mechanism of this injury is caused by the inhibitory action of cyclooxygenase
1 (COX 1). Recently, another inhibitor COX 2 with less inhibitory action
than COX 1 has been tested clinically. In fact, it is reported that application
of COX 2 inhibitor reduces the frequency of gastric mucosal injury. However,
since aspirin is used not only as anti inflammatory drug, but also for inhibition
of platelet aggregation, improvement of microcirculation and growth repression
of large intestine tumor, its clinical use is expected to remain popular.
Therefore, prevention of gastric mucosal injury caused by aspirin is extremely
important. The purpose of our study for the symposium is to examine effects
of alkaline ionized water against gastric mucosal injury in rats caused
by aspirin.
Test methods
Male Sprague Dawley rats (weighing 160 180g) were used. During 2 weeks of
testing, one of the groups was freely given alkaline ionized water (pH 10.5,
ORP 450rriV) produced by National TK780 electrolyzer. The other group, control
group was freely given tap water. Acute gastric mucosal injury was induced
by administering aspirin (200mg/kg) and hydrochloric acid (0.15N) in the
stomach of rats on a 18 day fast. Hemorrhagic erosions found on gastric
glands after periodic doses of aspirin underwent microscopic inspections,
and the sum of longer diameter of erosions was measured as the total erosion
(mm). Then, homogenate was created from scraped gastric mucosa treated with
phosphoric acid buffer to measure the level of inflammatory cytokine production
(TNF ~ a /cinc2 ~ ) as well as myeloperoxidase (MPO) activity as an index
of neutrophil infiltration based on given data. Each of these values was
adjusted by protein concentration.
Test results
1) No significant difference between the 2 groups was found as to weight,
physiological blood properties and antioxidant enzyme after raising them
for 2 weeks. The number of leukocyte in peripheral vessels has slightly
gone up.
2) Three hours after administering aspirin, erosive mucosal injury emerged
on the rats' stomach glands which was significantly inhibited for the alkaline
ionized water group.
3) MPO activity has significantly climbed after aspirin administration and
was inhibited in alkaline ionized water group.
4) Concentration of inflammatory creaking (TNF a /cinc2 in gastric mucosa
has significantly risen after aspinin administration, and was inhibited
by administration of alkaline ionized water.
Conclusion
Effect of alkaline ionized water against gastric mucosal injury caused by
aspirin, the representative NSAID, was confirmed. As part of its mechanism,
a possibility is indicated that inhibitory function of active neutrophil
and inflammatory cytokine production of alkaline ionized water is involved.
Recently, it was reported that TNF a plays a major role in triggering gastric
mucosal injury caused by aspirin and resulting in apoptosis of gastric mucosa.
We would like to further examine DNA fragmentation in vivo after aspirin
administration to study other effects of alkaline ionized water.
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