Healing of chronic gastroduodenal ulcerations by antacids. Role of prostaglandins and epidermal growth factor.
Antacids show gastroprotective action against various irritants in experimental animals and enhance the healing of chronic gastroduodenal ulcers in humans but the mechanisms of these effects are unknown. The present study was designed to determine whether prostaglandin (PG) and epidermal growth factor (EGF), which also have protective and antiulcer properties, contribute to the action of antacids on rat's stomach. It was found that Maalox 70 and its active component, Al(OH)3, enhance significantly the healing of chronic gastric and duodenal ulcers observed during 7 and 14 days after their induction. Pretreatment with indomethacin caused a significant prolongation of ulcer healing, and this was accompanied by a significant reduction in PG and EGF formation, suggesting that both factors may be involved in ulcer healing. Maalox and Al(OH)3 failed to prevent the suppression of PG by indomethacin but were equally effective in ulcer healing in rats without and with indomethacin administration, suggesting that endogenous PG may not play any important role in the healing process by these drugs. Removal of salivary glands, the major source of EGF, also prolonged ulcer healing but, again, Maalox was as effective in ulcer healing as in rats with intact salivary glands. Our findings that Maalox at pH above 3.0 binds significant amounts of EGF, enhances the binding of EGF to the ulcer area, and stimulates mucosal growth, suggest that EGF may be involved in ulcer healing; however, because antacids are also effective after sialoadenectomy, EGF does not seem to be the major factor in ulcer healing by these drugs.
Konturek
S J
SJ
Institute of Physiology, Academy of Medicine, Krakow, Poland.
Brzozowski
T
T
Drozdowicz
D
D
Dembinski
A
A
Nauert
C
C
D000536:Aluminum Hydroxide / Q000627:therapeutic use*; D000818:Animals; D000863:Antacids / Q000627:therapeutic use*; D004338:Drug Combinations / Q000627:therapeutic use; D004815:Epidermal Growth Factor / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D008274:Magnesium / Q000627:therapeutic use*; D008276:Magnesium Hydroxide / Q000627:therapeutic use*; D010437:Peptic Ulcer / Q000188:drug therapy*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology
D000863:Antacids; D004338:Drug Combinations; D011453:Prostaglandins; C013591:aluminum hydroxide, magnesium hydroxide, drug combination; D000536:Aluminum Hydroxide; D004815:Epidermal Growth Factor; D008274:Magnesium; D008276:Magnesium Hydroxide; D007213:Indomethacin