Effects of Nabumetone and Dipyrone on Experimentally Induced Gastric Ulcers in Rats
- PDF / 203,330 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 64 Downloads / 205 Views
Effects of Nabumetone and Dipyrone on Experimentally Induced Gastric Ulcers in Rats Engin Yıldırım,1,3 Oya Sağıroğlu,2 Fatma S. Kılıç,1 and Kevser Erol1
Abstract—Nabumetone and dipyrone are non-acidic, nonsteroidal anti-inflammatory drugs. Both of them are known to have weak inhibitory effects of cyclooxygenases. Gastric side effects represent the most common adverse drug effects of the widely used nonsteroidal anti-inflammatory drugs. The gastric effects of these drugs may be comparable in experimental ulcer models. In the present study, the gastric ulcerogenic activity of nabumetone and dipyrone were investigated on stress- and diethyldithiocarbamate-induced experimental ulcer models by determining the ulcer index and gastric mucus secretion in rats. It was found that diethyldithiocarbamate increased both ulcer index and mucus secretion. Nabumetone inhibited dose-dependently the increase of diethyldithiocarbamate-induced mucus secretion. Dipyrone inhibited both stress- and diethyldithiocarbamate-induced ulcer index and mucus secretion. Nabumetone inhibited stress-induced ulcer index at 25-mg/kg dose but stimulated dose-dependently mucus secretion. These effects may be attributed to their nonacidic structures and weak inhibitory effects on gastric mucosal cyclooxygenases. KEY WORDS: nabumetone; dipyrone; diethyldithiocarbamate; experimental ulcer models; gastric mucus secretion; rat.
diarrhea, but gastrointestinal ulceration appears to be lower than with other NSAIDs. Its active metabolite, 6methoxy-2-naphthylacetic acid, is a potent nonselective COX inhibitor. Its non-acidic chemical properties and COX-1/COX-2 inhibitor profile were suggested to be responsible for the low incidence of gastrointestinal ulcerations [4]. Dipyrone is known to be a prodrug and to have stronger analgesic and antipyretic and weaker antiinflammatory activities than the other NSAIDs. It is metabolized rapidly to 4-methylaminoantipyrine. This metabolite was found to inhibit COX-1 and COX-2 [5]. It has been shown to preferently inhibit COX-3 and COX-1 at a 6.6-fold higher concentration in vitro [6]. It was suggested that dipyrone inhibits COX activity through an independent mechanism from binding to the COX substrate channel [5]. The lack of acidity was proposed to be responsible for dipyrone’s favorable gastrointestinal tolerability compared with acidic NSAIDs. Diethyldithiocarbamate (DDC)-induced experimental ulcer model is known to be similar to human gastric ulcer [7–9]. It was reported that the multiple gastric lesions produced by DDC are only shallow and do not
INTRODUCTION The administration of traditional nonsteroidal antiinflammatory drugs (NSAIDs) is known to cause gastrointestinal complications and ulceration. NSAIDs are classified into non-selective COX inhibitors, selective COX-1 inhibitors, selective COX-2 inhibitors, and semiselective COX-2 inhibitors [1]. The beneficial effects of NSAIDs are attributed to their inhibitory activites of cyclooxygenase-2, whereas some of their adverse effects to their inhibitory activities of cycloox
Data Loading...
