Pathogenic Importance of Cysteinyl Leukotrienes in Development of Gastric Lesions Induced by Ischemia/Reperfusion in Mice

Abstract

We examined the role of cysteinyl leukotrienes (CysLTs) in the gastric ulcerogenic response to ischemia/reperfusion (I/R) in mice. Experiments were performed in male C57BL/6J mice after 18-h fasting. Under urethane anesthesia, the celiac artery was clamped for 30 min, and then reperfusion was achieved by removing the clamp. The stomach was examined for lesions 60 min thereafter. The severity of I/R-induced gastric damage was reduced by prior administration of pranlukast [CysLT receptorOn the contrary, these lesions were markedly worsened by pretreatment with indomethacin, and this response was abrogated by the coadministration of TMK688 or pranlukast. The gene expression of CysLT 1 R but not 5-LOX was up-regulated in the stomach after I/R, but both expressions were increased under I/R in the presence of indomethacin. I/R slightly increased the mucosal CysLT content of the stomach, yet this increase was markedly enhanced when the animals were pretreated with indomethacin. The increased CysLT biosynthetic response to indomethacin during I/R was attenuated by TMK688. Indomethacin alone caused a slight increase of CysLT 1 R expression and markedly up-regulated 5-LOX expression in the stomach. We concluded that I/R up-regulated the expression of CysLT 1 R in the stomach; CysLTs play a role in the pathogenesis of I/R-induced gastric damage through the activation of CysLT 1 R; and the aggravation by indomethacin of these lesions may be brought about by the increase of CysLT production and the up-regulation of 5-LOX expression, in addition to the decreased prostaglandin production.

Alpha‐Lipoic Acid Protects against Indomethacin‐Induced Gastric Oxidative Toxicity by Modulating Antioxidant System

“…NSAIDs cause gastric damage by interfering with prostaglandin synthesis, increasing acid secretion and back diffusion of H + ions, resulting in overproduction of leukotrienes and other products of the 5‐lipoxygenase pathway (Whittle 1981). IND also inhibits phospholipase‐A2, cysteinyl leucotriens, and lipooxygenase overexpression (Kaplan and others 1978; Nakamori and others 2010). However, ROS play an important role in the pathogenesis of mucosal damage caused by IND, ethanol, and other agents over the inhibition of cyclooxygenase (COX) enzymes (Elliot and Wallace 1998; Miura and others 2002; Koc and others 2008; Karakus and others 2009).…”

Activation of Muscarinic Acetylcholine Receptor Subtype 4 Is Essential for Cholinergic Stimulation of Gastric Acid Secretion: Relation to D Cell/Somatostatin

“…A portion of the PCR mixture was electrophoresed in 1.5% agarose gel in Tris-acetic acid-EDTA buffer (40 mM Tris, 20 mM acetic acid, and 2 mM EDTA; pH 8.1), and the gel was stained with ethidium bromide and photographed (Bio Doc-It Imaging System; UVP, Upland, CA, USA). Images were analyzed with the Image J (version 1.39), and the semi-quantitative measurement of mRNA expression was presented as a ratio compared with GAPDH (Nakamori et al, 2010; Hayashi et al, 2014). …”

Ameliorative potential of montelukast on ischemia–reperfusion injury induced vasculitic neuropathic pain in rat

“…In parenthesis indicated the dose in mg/kg. radicals as well as leukocyte synthesis and accumulation were contributed to ischemia-reperfusion injury (Minamisawa et al, 1988;Nakamori et al, 2010;Okubo et al, 2010aOkubo et al, , 2010b. Ischemiareperfusion injury induced vasculitic neuropathy has shown evidence for the role of myeloperoxidase (specific inflammatory marker) due to mast cell activation (Anderson et al, 1999;Jain et al, 2009).…”