0 1991 Raven Press, Ltd., New York
J Clin Gastroenterol 1991; 13 (Suppl. I ) : S 3 2 4 3 6 , 1991
Gastric Cytoprotection by Ornoprostil, a PGE, Analogue, in Human Subjects Kenzo Kobayashi, M.D., Ph.D., Tetsuo Arakawa, M.D., Kazuhude Higuchi, M.D., and Hajime Nakamura, M.D.
Prostaglandins (PGs) protect the gastric mucosa from damage caused by noxious agents such as absolute ethanol, strong acid, and boiling water in rats (1). This property of PGs, which is not related to inhibition of acid secretion, is referred to as “cytoprotection.” Histological and hemodynamic assessments have shown that PGs prevent deep necrosis, caused by ethanol and preserve microvascular circulation (2-5). These effects of PGs may contribute to the prevention of ethanol-induced visible mucosal lesions. There are only two reports pertaining to “cytoprotection” in humans (6,7). This study was done to test the effect of ornoprostil (a methyl derivative of PGE,) in a nonantisecretory dose on gastric mucosal damage caused by ethanol in human volunteers.
Ornoprostil, a methyl derivative of PGE, developed in Japan, was tested for its effect on gastric mucosal damage caused by ethanol in human subjects. Sixteen healthy volunteers were given either ornoprostil or a placebo, followed by 20 ml of 70% ethanol instilled into the gastric antral mucosa. Fifteen minutes later, visible mucosal lesions were evaluated endoscopically . The biopsy specimens were obtained from mucosa that had been exposed to ethanol but looked normal. The specimens were assessed by light microscopy and scanning electron microscopy. The gross mucosal damage demonstrated endoscopically was significantly less (p < 0.05) in the subjects receiving ornoprostil than those receiving placebo. Hyperemia and hemorrhage in the mucosa were also significantly less 0, < 0.05) in the subjects given ornoprostil pretreatment. Ornoprostil, however, failed to prevent the disruption of surface epithelial cells as assessed by scanning electron microscopy. These data suggest that ornoprostil protects gastric mucosa against damage caused by concentrated ethanol. Key Words: Cytoprotection-Prostaglandin-Ornoprostil-Gastric mucosa-Ethanol-Scanning electron microscopy-Endoscopy .
SUBJECTS AND METHODS Subjects Sixteen healthy male volunteers (characteristics shown in Table 1) were divided into two groups of 7 and 9 subjects to be treated with ornoprostil or a placebo, respectively. There was no difference in age, smoking, or drinking habits between the two groups (Table 1). The subjects had abstained from cigarettes, alcoholic beverages, and any medication for 2 weeks before the test. They gave written informed consent to participate in the study after a full explanation of the purpose of the study and the experimental design.
Experimental Design Seven subjects were given 5 pg of ornoprostil orally for 24 h ; the other nine subjects were given a placebo. One hour after the last dose, gastrofiberscopy was done by a physician unaware of treatment. Twenty milliliters of 70% ethanol were instilled via a polyethylene tube (through the channel of the fiberscope) to the posterior wall of the gastric antrum within a few seconds and was kept there for 15 min by positioning the subject supine with slight elevation of the left half of the body. The
From the Third Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan. Address correspondence and reprint requests to Dr. K. Kobayashi at Third Department of Internal Medicine, Osaka City University Medical School, 1-5-7 Asahimachi, Abeno, Osaka 545, Japan.
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J Clin Gastroenterol 1991; 13 (Suppl. I ) : S 3 2 4 3 6 , 1991
Gastric Cytoprotection by Ornoprostil, a PGE, Analogue, in Human Subjects Kenzo Kobayashi, M.D., Ph.D., Tetsuo Arakawa, M.D., Kazuhude Higuchi, M.D., and Hajime Nakamura, M.D.
Prostaglandins (PGs) protect the gastric mucosa from damage caused by noxious agents such as absolute ethanol, strong acid, and boiling water in rats (1). This property of PGs, which is not related to inhibition of acid secretion, is referred to as “cytoprotection.” Histological and hemodynamic assessments have shown that PGs prevent deep necrosis, caused by ethanol and preserve microvascular circulation (2-5). These effects of PGs may contribute to the prevention of ethanol-induced visible mucosal lesions. There are only two reports pertaining to “cytoprotection” in humans (6,7). This study was done to test the effect of ornoprostil (a methyl derivative of PGE,) in a nonantisecretory dose on gastric mucosal damage caused by ethanol in human volunteers.
Ornoprostil, a methyl derivative of PGE, developed in Japan, was tested for its effect on gastric mucosal damage caused by ethanol in human subjects. Sixteen healthy volunteers were given either ornoprostil or a placebo, followed by 20 ml of 70% ethanol instilled into the gastric antral mucosa. Fifteen minutes later, visible mucosal lesions were evaluated endoscopically . The biopsy specimens were obtained from mucosa that had been exposed to ethanol but looked normal. The specimens were assessed by light microscopy and scanning electron microscopy. The gross mucosal damage demonstrated endoscopically was significantly less (p < 0.05) in the subjects receiving ornoprostil than those receiving placebo. Hyperemia and hemorrhage in the mucosa were also significantly less 0, < 0.05) in the subjects given ornoprostil pretreatment. Ornoprostil, however, failed to prevent the disruption of surface epithelial cells as assessed by scanning electron microscopy. These data suggest that ornoprostil protects gastric mucosa against damage caused by concentrated ethanol. Key Words: Cytoprotection-Prostaglandin-Ornoprostil-Gastric mucosa-Ethanol-Scanning electron microscopy-Endoscopy .
SUBJECTS AND METHODS Subjects Sixteen healthy male volunteers (characteristics shown in Table 1) were divided into two groups of 7 and 9 subjects to be treated with ornoprostil or a placebo, respectively. There was no difference in age, smoking, or drinking habits between the two groups (Table 1). The subjects had abstained from cigarettes, alcoholic beverages, and any medication for 2 weeks before the test. They gave written informed consent to participate in the study after a full explanation of the purpose of the study and the experimental design.
Experimental Design Seven subjects were given 5 pg of ornoprostil orally for 24 h ; the other nine subjects were given a placebo. One hour after the last dose, gastrofiberscopy was done by a physician unaware of treatment. Twenty milliliters of 70% ethanol were instilled via a polyethylene tube (through the channel of the fiberscope) to the posterior wall of the gastric antrum within a few seconds and was kept there for 15 min by positioning the subject supine with slight elevation of the left half of the body. The
From the Third Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan. Address correspondence and reprint requests to Dr. K. Kobayashi at Third Department of Internal Medicine, Osaka City University Medical School, 1-5-7 Asahimachi, Abeno, Osaka 545, Japan.
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