Intestinal Dysmotility and Associated Disorders in Intestinal Muscle of Methylglyoxal-Treated Mice.

Abstract

Background: Peritoneal dialysis (PD) is a renal replacement therapy approach to treat end-stage renal failure. However, complications such as gastrointestinal dysmotility occur in patients undergoing PD, and the mechanisms underlying these complications have not been elucidated. We hypothesized that inflammation and dysfunction of the interstitial cells of Cajal (ICC) contribute to the PD-induced gastrointestinal dysmotility.

Methods: Mice were intraperitoneally administered a dialysate containing methylglyoxal (40 mM) every other day for 2 weeks to mimic the gastrointestinal complications in patients undergoing long-term PD. The gastrointestinal transit capacity was evaluated using fluorescent dyes that were forcibly administered orally. To evaluate the inflammation and function of the ICC in the intestinal muscles, we performed real-time polymerase chain reaction and immunohistochemical staining and measured spontaneous contractions ex vivo.

Key results: The intestinal transit capacity was significantly reduced in the methylglyoxal-treated group compared to that in the control group. In the inflammatory evaluation, the number of neutrophils and macrophages in the intestinal muscles significantly increased in the methylglyoxal-treated group compared to the control group. Moreover, the mRNA expression levels of Tnf, Il1b, and Il6 were upregulated in the intestinal muscle from the methylglyoxal-treated group. The mRNA expression of Kit, an interstitial cell of Cajal marker, was significantly decreased in the methylglyoxal-treated group. In addition, the frequency of spontaneous contractions, an index of ICC function, was decreased in the methylglyoxal-treated group.

Conclusions and inference: Our data suggest that the PD-induced gastrointestinal dysmotility might be due to inflammation and dysfunction of the ICC in intestinal muscles.