Intestinal alkaline phosphatase decreases intraperitoneal adhesion formation.

ABSTRACT

BACKGROUND: Damage to the peritoneum initiates an inflammatory response leading to the formation of adhesions, which subsequently cause significant morbidity in some patients. Intestinal alkaline phosphatase (IAP) is a gut enzyme capable of detoxifying various inflammatory mediators such as lipopolysaccharide, lipoteichoic acid, CpG DNA, and adenosine triphosphate. In this study, we aimed to examine the anti-inflammatory effects of IAP on postoperative adhesions in mice. METHODS: C57BL/6 mice were subjected to a midline laparotomy and then six musculoperitoneal buttons (MPBs) were created by pinching and ligating the peritoneum and underlying muscle. The buttons were half-excised and E-cauterized, and then cecal abrasion was performed. Five hundred microliters of vehicle with IAP 5000 U or vehicle alone were applied over the peritoneal cavity. In some experiments, the mice were euthanized on the first and second postoperative day (POD), and cytokines analysis was done on the MPB, peritoneal tissue, and peritoneal fluid. In separate experiments, the mice were sacrificed on the 21st POD, and adhesion to each button was scored based on type and tenacity. RESULTS: IAP group mice had significantly lower adhesion scores compared with controls (21.5 ± 1.7 versus 13.2 ± 1.3; P = 0.0014, n = 15). MPB from IAP group mice had significantly lower interleukin-1ß and tumor necrosis factor-α protein level compared to control mice (105.66 ± 4.5 versus 69.8 ± 4.8 versus pg/mg, P = 0.0001; 45.25 ± 2.8 pg/mg versus 24.88 ± 4.1 pg/mg; P = 0.0007, n = 10). IAP treatment significantly decreased interleukin-1ß and tumor necrosis factor-α mRNA expression in MPB in the first POD (1.14 ± 0.25 versus 0.33 ± 0.07; P = 0.0068; 1.33 ± 0.31 versus 0.33 ± 0.08; P = 0.0064, n = 10). CONCLUSIONS: Application of IAP during laparotomy could represent a novel approach to prevent postoperative adhesions.