Sodium butyrate inhibits necroptosis in intestinal epithelial cells during liver cirrhosis, highlighting its potential to protect the intestinal barrier.

Sodium butyrate modulates necroptosis in intestinal epithelial cells during liver cirrhosis, offering potential therapeutic insights for intestinal barrier protection.

Background and Aims

Necroptosis plays a crucial role in regulating intestinal epithelial cells (IECs). Butyric acid (BA), a product of intestinal microbial metabolism, helps maintain the intestinal epithelial barrier. However, it is not yet known whether necroptosis occurs in IECs during liver cirrhosis, or whether sodium butyrate (NaB) can modulate this process. This study explores whether IECs undergo necroptosis in the context of cirrhosis and whether NaB can influence necroptosis and the associated regulatory mechanisms (1^✔ ✔Trusted Source
Sodium Butyrate Inhibits Necroptosis by Regulating MLKL via E2F1 in Intestinal Epithelial Cells of Liver Cirrhosis

Go to source

).

Methods

Serum levels of RIPK3(Receptor-Interacting Protein Kinase 3), MLKL(Mixed lineage kinase domain-like), and Zonulin, as well as fecal BA levels, were measured and correlated in 48 patients with liver cirrhosis and 20 healthy controls. A rat model of liver cirrhosis was established, and NaB was administered. The expressions of MLKL, p-MLKL(Phosphorylated MLKL), and tight junction proteins were measured. We conducted an in vitro investigation of the effect of NaB on necroptosis in the HT29 cell line.

Results

Serum levels of RIPK3, MLKL, and Zonulin in the liver cirrhosis group were higher, while fecal BA levels were lower than those in the control group. Zonulin levels were positively correlated with RIPK3 and MLKL levels, while fecal BA levels were negatively correlated with serum MLKL levels, but not with RIPK3 levels. NaB reduced the mRNA and protein expression of MLKL but did not effect RIPK1 and RIPK3 in-vitro. Rescue experiments demonstrated that NaB inhibited necroptosis through E2F1-mediated regulation of MLKL.

Conclusions

NaB alleviates intestinal mucosal injury and reduces necroptosis in IECs in liver cirrhosis. It also inhibits the necroptosis of IECs and protects the intestinal barrier by reducing E2F1 expression and downregulating MLKL expression levels. These results can be employed to develop a novel strategy for treating complications arising from liver cirrhosis.

Reference:

1. Sodium Butyrate Inhibits Necroptosis by Regulating MLKL via E2F1 in Intestinal Epithelial Cells of Liver Cirrhosis – (https://www.xiahepublishing.com/2310-8819/JCTH-2024-00221)

Source-Eurekalert