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Abstract
Ileus continues to be a common consequence of abdominal surgery, causing significant
patient discomfort and often leading to more serious problems. The therapy available
is limited, hence, ileus remains an important clinical problem. Activation of inducible
nitric oxide synthase (iNOS) directly modulates intestinal dysmotility after bowel
manipulation and plays an essential role in initiating intestinal inflammation. Nuclear
factor (NF)-kappaB is known to be a critical component of iNOS gene transcriptional
activation in response to inflammatory stimuli. Bromelain is a crude extract from
the pineapple stem, which is sold as a nutritional supplement to "promote digestive
health" and as an anti-inflammatory medication in some developed countries. Here,
we have found that oral administration of bromelain improves decrease in defecation
in abdominal postoperative rats. Results showed that bromelain increased the wet weight,
dry weight, water content and number of fecal pellets in laparotomized plus mechanically
manipulated rats, suggesting improvement of postoperative ileus. Furthermore, bromelain
treatment inhibited overexpressed iNOS mRNA and restored down-regulated inhibitor
kappaBalpha mRNA in the colon of the postoperative rats. From the in vitro experiments,
bromelain inhibits lipopolysaccharide (LPS)-induced nitrite overproduction in macrophage
cell lines and LPS-induced NF-kappaB luciferase reporter gene expression in RAW264.7
macrophages transfected with NF-kappaB luciferase reporter gene. Thus, our findings
suggest that bromelain improves decrease in defecation in postoperative rats, at least
in part, by inhibiting colonic iNOS overexpression via NF-kappaB pathway. Our data
indicates that bromelain may benefit patients with postoperative ileus.