Prostaglandin, tumor necrosis factor alpha and neutrophils: causative relationship in indomethacin-induced stomach injuries

European Journal of Pharmacology
S Z DingC H Cho

Abstract

Tumor necrosis factor alpha (TNF-alpha) has been suggested to play a critical role in indomethacin-induced gastric mucosal damage, so we evaluated its mucosal level and its relationship with prostaglandin E2 and neutrophils in indomethacin-induced gastric mucosal injury in rats. Indomethacin caused a time- and dose-dependent increase in gastric mucosal erosion, which was accompanied by a reduction in prostaglandin E2 followed by an increase in TNF-alpha level and neutrophil infiltration in the gastric mucosa. Pretreatment with exogenous prostaglandin E2 totally abolished indomethacin-induced gastric mucosal injury and the TNF-alpha increase. Depletion of neutrophils by methotrexate or reduction of TNF-alpha concentration by pentoxifylline markedly reduced indomethacin-induced mucosal damage. Pentoxifylline but not methotrexate prevented the increase in mucosal TNF-alpha level induced by indomethacin. It is suggested that depletion of prostaglandin E2 followed by an increase of TNF-alpha production and neutrophil infiltration in the gastric mucosa are important sequential processes in indomethacin-induced ulceration. Prevention of one of these processes would inhibit ulcer formation.

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Citations

Jun 7, 2000·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·R E Kast
Oct 30, 1999·Alimentary Pharmacology & Therapeutics·Y Li, C H Cho
Jul 12, 2001·Journal of Gastroenterology and Hepatology·E S LiuC H Cho
Feb 24, 2001·Biological & Pharmaceutical Bulletin·J TanakaT Yamakawa
May 31, 2014·Evidence-based Complementary and Alternative Medicine : ECAM·Gehan Moustafa Badr, Jawaher Abdulaziz Al-Mulhim
Nov 6, 2007·European Journal of Pharmacology·Debashish BanerjeeSubrata Chattopadhyay
Nov 19, 2010·International Immunopharmacology·Hanumantha Rao Balaji RaghavendranSathyanath Rekha
Dec 1, 2005·Phytotherapy Research : PTR·Shoba NarayanC S Shyamala Devi
Dec 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M R GrafR E Merchant
Mar 15, 2003·The Journal of Pharmacy and Pharmacology·Yoshiro IshiwataToshikazu Yoshikawa
Apr 13, 2006·World Journal of Gastroenterology : WJG·Kallaya EamlamnamDuangporn Thong-Ngam
Oct 7, 2020·Clinical and Experimental Pharmacology & Physiology·Gisele Maziero AlvesBianca Prandi Campagnaro
Oct 22, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Lifeng QiuJianmin Si
May 23, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Elisabetta GianazzaIngrid Miller

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