W1695 Effect of Allyl Isothiocyanate, a Pungent Ingredient of Wasabi and Mustard Oil, on Gastric Mucosal Blood Flow and Ulcerogenesis in Rats: Comparison With Capsaicin

Abstract

arginine (200 mg/kg i.g.); 2) calcitonin gene related peptide (CGRP 5 μg/kg s.c.) and low dose of capsaicin (0.5 mg/kg i.g.) capable of stimulating sensory afferents on ischemia/ reperfusion (I/R, 30 min of ischemia to celiac artery followed by 3 hrs of reperfusion) injury (series A)and the healing of chronic acetic acid ulcers (ulcer area = 28 mm2) in rats with intact and capsaicin-deactivated sensory nerves (series B). The area of gastric lesions and ulcers was determined by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance method, NOx gastric content, plasma MPO activity and the mucosal activity of antioxidazing enzymes SOD, GPx and MDA concentration as an index of oxygen radicallipid peroxidation were assessed. The gastric content of ADMA was determined by HPLC method and gastric mucosal expression of transcription factor NFκB, IL-1β and TNF-α mRNAs their plasma levels were analyzed by RT-PCR and ELISA. I/R produced gastric lesions (series A) accompanied by an increase in plasma ADMA, MDA, MPO contents, the fall in the GBF by 31% and the suppression of SOD and GPx activities. ADMA which significantly reduced the luminal NOx content, dose-dependently aggravated I/R damage and significantly delayed the healing of acetic acid ulcers (series B); both effects being worsened by capsaicin denervation. These effects were accompanied by further fall in the GBF and a significant decrease in the SOD and GPx activities and the significant increase in MDA content. The ADMA delay in ulcer healing was accompanied by the upregulation of NFκB, IL-1β and TNF-α mRNAs at ulcer margin followed by the rise in plasma IL-1β, TNF-α and ADMA levels and these effects were markedly diminished by addition of L-Arg, CGRP or capsaicin to ADMA. We conclude that: 1) ADMA plays an important role in the pathogenesis of acute gastric lesions induced by I/R and delays ulcer healing due to the inhibition of NO generation, NFκB activation, overexpression of proinflammatory cytokines IL-1β and TNF-α and enhancement in lipid peroxidation; 2) L-Arg, a donor of NO or sensory nerve vasodilatory neuropeptide CGRP counteract the ADMA-induced facilitation of mucosal lesions and the impairment of the healing of preexisting gastric ulcers.