Treatment of mice with cromolyn sodium after reperfusion, but not prior to ischemia, attenuates small intestinal ischemia-reperfusion injury

Gan,Xiaoliang; Liu,Dezhao; Ge,Mian; Luo,Chenfang; Gao,Wanling; Hei,Ziqing

doi:10.3892/mmr.2013.1591

Treatment of mice with cromolyn sodium after reperfusion, but not prior to ischemia, attenuates small intestinal ischemia-reperfusion injury

Authors:
- Xiaoliang Gan
- Dezhao Liu
- Mian Ge
- Chenfang Luo
- Wanling Gao
- Ziqing Hei
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Affiliations: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
Published online on: July 17, 2013 https://doi.org/10.3892/mmr.2013.1591
Pages: 928-934

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Abstract

Stabilizing mast cells (MCs) can either inhibit or augment inflammation; however, how improved therapeutic benefits against small intestinal ischemia-reperfusion injury (IIRI) can be achieved by stabilizing MCs remains to be elucidated. The present study was designed to evaluate different treatments with cromolyn sodium (CS, an MC stabilizer), which was administrated either prior to ischemia or after reperfusion. Kunming mice were randomized into a sham-operated group (SH), a sole IIR group (M), in which mice were subjected to 30 min superior mesenteric artery occlusion followed by 3 day or 3 h reperfusion, or IIR, treated with CS 15 min prior to ischemia or 15 min after reperfusion in the PreCr and PostCr groups. The survival rate and Chiu's scores were evaluated. The levels of ET-1, histamine, TNF-α and IL-6, and expression of MC protease 7 (MCP7), MC counts and myeloperoxidase (MPO) activity were quantified. IIR resulted in severe injury as demonstrated by significant increases in mortality and injury score. IIR also led to substantial elevations in the levels of ET-1, histamine, TNF-α and IL-6, expression of MCP7, MC counts and MPO activities (P<0.05, M vs. SH groups). All biochemical changes were markedly reduced in the PostCr group (P<0.05, PostCr vs. M groups), whereas pretreatment of IIR mice with CS prior to ischemia exhibited no changes of ET-1 levels, injury score and inflammation (P>0.05, PreCr vs. M groups). In conclusion, administration of CS after reperfusion, but not prior to ischemia, attenuates IIRI by downregulating ET-1 and suppressing sustained MC activation.

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