Prostaglandin protection of the human gastric mucosa against alcohol-induced injury. Endoscopic, histologic, and functional assessment.

UNLABELLED: We studied whether pretreatment with prostaglandin (16,16-dimethyl (dm) prostaglandin E2) may protect the human gastric mucosa against alcohol-induced injury. Healthy volunteers received (via an endoscope) intragastric pretreatment with either: A) placebo or B) 16,16 dm prostaglandin E2, 1 microgram/kg, and 15 min later 40 ml 60% alcohol was sprayed directly on gastric mucosa. STUDIES: endoscopic appearance of the gastric mucosa was evaluated and scored (scale 0-5) by two investigators, gastric mucosal potential difference (PD) was continuously recorded, and mucosal biopsies were obtained at 30 min after alcohol for histologic examination. Alcohol instillation in subjects pretreated with placebo (group A) produced within 30 min prominent endoscopic hemorrhagic lesions (grade 4.8 +/- 0.2). Histologic examination showed exfoliation of the surface epithelium, extensive edema of lamina propria, and deep hemorrhagic necrotic lesions in 86% +/- 10 of specimens. These morphologic changes coincided with a sudden drop in gastric PD of 42 mV. Prostaglandin pretreatment (group B) significantly reduced alcohol-induced endoscopically visible lesions (grade 3.1 +/- 0.2, P less than 0.01 vs group A). Histologically, prostaglandins reduced deep hemorrhagic erosions (4.5-fold reduction) and subepithelial hemorrhages, but did not prevent exfoliation of the surface epithelium and gastric PD drop. Thus, prostaglandin administration to human volunteers effectively reduced alcohol injury to the gastric mucosa.

Alcohol injury to the normal human gastric mucosa: endoscopic, histologic and functional assessment.

In 15 healthy volunteers, we studied the effect of intragastric administration of 100 ml 40% alcohol (in 10 experimental subjects) or isotonic saline (in 5 control subjects) on endoscopic appearance of the gastric mucosa, mucosal histology, luminal pH, and gastric mucosal potential difference. We found that a single dose of 40% alcohol produces rapid endoscopic changes (congestion and focal hemorrhagic lesions) and prominent histologic changes (exfoliation of the surface epithelium, edema of the lamina propria and hemorrhagic lesions associated with mucosal microvascular damage). The histologic changes were seen as early as 5 minutes after alcohol administration and occurred coincidentally with functional changes, which consisted of a sudden increase in luminal pH and a drop in the mucosal potential difference. The present study correlates the time sequence of the endoscopic, histological, and functional changes of the gastric mucosa following acute alcohol injury in normal human volunteers. This study confirms that many of the previous observations in animal models are also seen in normal human volunteers.

Ethanol induced duodenal lesions in man. Protective effect of prostaglandin.

This study aimed: 1. to investigate quantitatively mucosal changes in the human duodenum after ethanol instillation, 2. to determine the effect of 16,16 dimethyl prostaglandin E2 (dmPGE2) pretreatment on these changes. In 11 healthy subjects were instilled into the postbulbar duodenum solutions of normal saline or dmPGE2 and 15 minutes later 20 ml 40% ethanol. Mucosal changes were evaluated endoscopically and histologically. Thirty minutes after ethanol and saline, hemorrhagic changes involved the entire mucosa (endoscopic lesion index: 4.8 +/- 0.2) and all histological specimens showed erosions. Pretreatment with dmPGE2 significantly prevented ethanol-induced mucosal changes (endoscopic lesion index: 2.17 +/- 0.17 p less than 0.01) and mucosal biopsies did not show erosions outside endoscopically abnormal areas. In conclusion, direct instillation of ethanol induced consistent damage to duodenal mucosa in man. This damage was significantly reduced by dmPGE2 pretreatment.

Cytoprotective effect of 16, 16' dimethyl prostaglandin E2 and some drugs on an acute galactosamine induced liver damage in rat.

Present experiment was aimed to study whether 16, 16' dimethylprostaglandin E2 (dmPGE2), Hepatofalk (HF), or Orotofalk (OF) may prevent an acute liver damage induced in rats with D-galactosamine (GalN). Fifty male rats were divided into 5 groups: 1. controls, 2. rats receiving GalN 750 mg/kg b. w. intraperitoneally, 3. animals pretreated with 5 microgram/kg dmPGE2 given subcutaneously 24 hours prior to, 30 min prior to and 6 hours after GalN. Rats of group 4 received HF 0,8 ml/kg intramuscularly and group 5 OF 0,3 caps/kg intragastrically 24 hours prior to, 30 min prior to and 6 hours after GalN. Animals were sacrificed 24 hours after GalN injection. Histological, histochemical and ultrastructural studies of the liver were performed. In rats receiving GalN alone (group 2) typical severe liver damage consisting of acidophilic necrosis of hepatocytes, periportal and intralobular inflammatory infiltration, hypertrophy and hyperplasia of Browicz-Kupffer cells has been observed. Histochemical investigations showed in this group fatty degeneration and a decrease in glycogen content in hepatocytes, irregular distribution of lysosomes, numerous cytolysosomes and uneven decrease in lysosomal enzymes activity (acid phosphatase and beta-glucuronidase). Ultrastructural studies revealed depletion in glycogen, fat droplets, hypertrophy of smooth endoplasmic reticulum and numerous autophagic vacuoles. Some of these vacuoles or residual bodies were dropping out into intercellular space. Focal accumulation of lamellar cytomembranes as well as condensation of heterochromatin in nuclei were also observed. Pretreatment of animals with dmPGE2 (group 3), HF (group 4) or OF (group 5) prior to GalN prevented liver cell necrosis. Histological, histochemical and ultrastructural picture of the liver was in these groups close to normal. Only very slight hypertrophy and hyperplasia of Browicz-Kupffer cells, was seen as well as depletion of glycogen and hypertrophy of smooth endoplasmic reticulum in hepatocytes. We conclude dmPGE2, HF and OF offered impressive cytoprotection against GalN induced liver damage in rat.

Prostaglandin protection of carbon tetrachloride-induced liver cell necrosis in the rat.

We studied whether 16,16--dimethyl prostaglandin E2 (dmPGE2) may prevent acute liver damage induced by carbon tetrachloride (CCl4) in the rat. One hundred thirty male rats were divided into the following groups: (1) controls, (2) rats given CCl4 6670 mg/kg body wt subcutaneously, (3) rats pretreated with 5 micrograms/kg dmPGE2 given subcutaneously 30 min before, and 8 and 24 h after CCl4 administration, and (4) animals given dmPGE2 only as in group 3. Liver damage was assessed by biochemical studies (SGPT, serum alkaline phosphatase, and bilirubin) and by histology. In rats receiving CCl4 alone, SGPT activities were significantly elevated to 1024 +/- 82 U/L, 1270 +/- 120 U/L, 386 +/- 48 U/L and 208 +/- 20 U/L at 24, 48, 96, and 120 h after CCl4 respectively. In animals pretreated with dmPGE2 before CCl4, SGPT activities were 201 +/- 24 U/L, 55 +/- 4.6 U/L, 28 +/- 4 U/L, and 24 +/- 4 U/L at 24, 48, 96, and 120 h after CCl4, respectively (p less than 0.01, versus animals receiving CCl4 only). Histologically, livers of rats treated with CCl4 alone showed severe centrilobular necrosis at 24 and 48 h. Livers of animals pretreated with dmPGE2 before CCl4 did not show necrosis. It is concluded that dmPGE2 protects the liver against cell necrosis induced by CCl4 in the rat.