Amifostine (Wr-2721) prevents indomethacin-induced gastric damage in rats: role of non-protein sulfhydryl groups and leukocyte adherence.
This study was designed to evaluate the protective effect of amifostine on indomethacin-induced gastric damage, and the role of increased gastric non-protein sulfhydryl groups (NP-SH) and decreased leukocyte adherence in this event. Wistar rats were pretreated with amifostine (10, 30, or 90 mg/kg intraperitoneal (i.p.) or subcutaneous (s.c.)) or saline. After 30 min, the rats received indomethacin (20 mg/kg, by gavage) and were then killed 3 hr later. Macroscopic and microscopic gastric damage, concentration of gastric NP-SH, prostaglandin E2 (PGE2), and mesenteric leukocyte adherence (intravital microscopy) were assessed. Amifostine prevented significantly (P < 0.05), macroscopic or microscopic, indomethacin-induced gastric damage, and increased gastric NP-SH, in a dose-dependent manner, with a maximal effect at a dose of 90 mg/kg. Subcutaneous, but not i.p., amifostine administration decreased (P < 0.05) the indomethacin-induced increase in leukocyte adherence. Indomethacin-induced PGE2 depletion was not reversed by amifostine. Amifostine has a protective effect against indomethacin-induced gastropathy by increasing gastric NP-SH and decreasing leukocyte adherence.
Mota
José Maurício S C
JM
Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Soares
Pedro M G
PM
Menezes
Alvaro A J
AA
Lemos
Henrique P
HP
Cunha
Fernando Q
FQ
Brito
Gerly Anne C
GA
Ribeiro
Ronaldo A
RA
de Souza
Marcellus H L P
MH
D000268:Adhesiveness; D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005905:Glyburide / Q000494:pharmacology; D007150:Immunohistochemistry; D007213:Indomethacin / Q000009:adverse effects*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013272:Stomach Diseases / Q000209:etiology / Q000517:prevention & control*; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D011837:Radiation-Protective Agents; D013438:Sulfhydryl Compounds; D015232:Dinoprostone; D004999:Amifostine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin