Are all "cytoprotective" drugs gastroprotective?
The effect of three--structurally different--groups of compounds was compared against gastric mucosal damages induced by ethanol or prostaglandin (PG) synthesis inhibitors, as well as against carrageenan-induced inflammation. All the compounds studied--SH-compounds (cysteamine, 2,3-dimercaptosuccinic acid, D,L-penicillamine), SH-blocking N-ethylmaleimide (NEM) and morphine-exerted dose-dependent inhibition on carrageenan edema test and against ethanol-induced gastric damage. Mucosal lesions induced by PG synthesis inhibitors (indomethacin 20 mg/kg, naproxen 75 mg/kg, piroxicam 60 mg/kg) were inhibited by drugs studied when the compounds were given before the damaging agents. However, when the drugs were injected 1 h after the inhibitors of PG synthesis opposite actions were observed; SH-compounds exerted protective, while NEM (2 mg/kg p.o.) and morphine (5 mg/kg p.o.) aggravating action. The results suggest that: 1. SH-compounds might have therapeutic importance in the treatment of gastric damage induced by prostaglandin synthesis inhibitors. 2. Reconsideration of the use of the term "cytoprotection" is necessary, since "cytoprotective" agents may aggravate mucosal damage in other ulcer model.
Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.
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K
Gyires
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002351:Carrageenan; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D000431:Ethanol; D005260:Female; D008297:Male; D009020:Morphine / Q000494:pharmacology; D011448:Prostaglandin Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D016861:Cyclooxygenase Inhibitors; D011448:Prostaglandin Antagonists; D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D000431:Ethanol; D009020:Morphine; D002351:Carrageenan