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Delay of Hepatic Ischemia‐Reperfusion Injury by Acetylcholine Receptor Agonist
Author(s) -
Crockett Elahe T,
Pandya Kinnari
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1072-b
Subject(s) - cholinergic , reperfusion injury , medicine , cytokine , endocrinology , agonist , nicotine , ischemia , alanine transaminase , tumor necrosis factor alpha , liver injury , pharmacology , chemistry , receptor
Recent studies have shown that cholinergic pathway stimulation exhibits anti‐inflammatory properties through inhibition of tumor necrosis factor (TNF). Cytokine production is a critical component of ischemia/reperfusion (IR) injury. This study examined the role of cholinergic pathway in cytokine production and hepatic IR‐injury. Methods Adult male mice underwent 90 min of lobar liver ischemia followed by 3, 6, and 24 hr of reperfusion. The acetylcholine receptor (AchR) agonists, DMPP, and nicotine were administered i.p. before ischemia. Plasma cytokine TNF‐α, macrophage inflammatory protein (MIP)‐2, and IL‐6 were measured. Liver injury was assessed by plasma alanine transaminase (ALT) and histopathology. Results A reperfusion time‐dependent hepatocellular injury occurred as indicated by increased plasma‐ALT and histopathology. The injury was associated with marked elevation of plasma cytokines/chemokines. Pre‐ischemic treatment of mice with DMPP or nicotine significantly decreased plasma‐ALT and cytokines after 3‐hr of reperfusion. After 6‐hr of reperfusion, the protective effect of DMPP decreased and reached a negligible level by 24‐hr of reperfusion although plasma cytokines remained significantly low. Histopathology showed markedly diminished hepatic injury in DMPP‐ or nicotine‐pretreated mice during the early‐phase of hepatic‐IR, which reached a level comparable to saline‐treated mice at late‐phase of IR. Conclusions Pharmacological modulation of the cholinergic pathway through AchR provides a means to regulate cytokine production and delay IR‐induced hepatic injury.