Dual Action of Nitric Oxide in the Pathogenesis of Ischemia/Reperfusion-Induced Mucosal Injury in Mouse Stomach

Abstract

Aim: We investigated the roles of NO/NOS isoforms in the pathogenesis of ischemia/reperfusion (I/R)-induced gastric injury in mouse stomachs. Methods: Under urethane anesthesia, the celiac artery was clamped, and then reperfusion was established 30 min later by removal of the clamp. After a 60-min reperfusion, the stomach was examined for macroscopic lesions. Results: Following I/R, hemorrhagic lesions were generated in the mucosa, although ischemia alone caused no visible damage. Prior administration of L-NAME (a nonselective NOS inhibitor) significantly aggravated these lesions, in a L-arginine-inhibitable manner. By contrast, the selective iNOS inhibitor 1400W significantly prevented the occurrence of I/R-induced gastric lesions. The mucosal MPO activity was increased after I/R, and this response was enhanced and attenuated by prior administration of L-NAME and 1400W, respectively. Interestingly, the later treatment with L-NAME, given 10 min before reperfusion, significantly reduced the severity of the I/R-induced gastric damage, in a L-arginine-dependent manner. The expression of iNOS mRNA was up-regulated in the stomach following I/R, with an increase of mucosal NO content, and the NO production was significantly inhibited by both L-NAME and 1400W. Conclusion: Endogenous NO plays a dual role in the pathogenesis of IR-induced gastric damage; NO/cNOS is protective while NO/iNOS is proulcerogenic during I/R.

Protective effect of rutin against acute gastric mucosal lesions induced by ischemia-reperfusion

“…MPO activity was a marker to assay neutrophil infiltrations (Tiidus et al, 2005). In the present study, we observed a significant increase in MPO activity in the stomach after I/R, which was in agreement with previous research (Gou et al, 2011;Kobata et al, 2007), confirming the infiltration and activation of neutrophils in the gastric mucosa during I/R. However, the increased MPO activity induced by I/R was significantly inhibited by prior administration of rutin.…”

“…Gastric I/R leads to tissue injury in gastric mucosa (Gou et al, 2011;Kobata et al, 2007). This study indicated a significant increase of lipid peroxidation and MPO activity, which were accompanied by alterations of cNOS and iNOS activities in the gastric mucosa induced by I/R.…”

“…It has been demonstrated that NO, NO donors and NOS activation or transgenic over-expression exert protective effects in a number of experimental models of I/R (Andrews et al, 1994b;Lefer, 1995) and that the suppression of inducible nitric oxide synthase (iNOS) improves gastric I/R injury. However, other studies reported harmful effect on gastric mucosal lesions of NO (Kobata et al, 2007;Nishio et al, 2006). Woolfson et al (1995) also revealed a damaging effect of NO-exposure, suggesting a critical role of dose and duration of NO-exposure and indicating a narrow therapeutic safety window for NO in I/R pathophysiology.…”

“…MPO activity in the gastric mucosa was measured by the o-dianisidine method (Kobata et al, 2007). The gastric mucosa tissue samples were homogenized in 50 mM phosphate buffer (pH 6.0) containing 0.5% hexadecyltrimethylammonium bromide.…”

A preliminary study of the anti-inflammatory and anti-apoptotic effects of crocin against gastric ischemia-reperfusion injury in rats

“…It has been shown that mRNA and protein expression of iNOS is upregulated following gastric I/R injury in mice and rats (Kobata et al, 2007;Yi et al, 2012). Consistent with these findings, the present study demonstrated that iNOS protein expression drastically increased after I/R injury in the rat stomach.…”