Rifaximin Prevents Intestinal Barrier Dysfunction and Alleviates Liver Injury in MCT-induced HSOS Mice

Abstract

Objective

Rifaximin is an effective component of treatment strategies for liver and intestinal diseases. However, the efficacy of rifaximin in hepatic sinusoidal obstruction syndrome (HSOS) has not been explored. The present study aimed to investigate the efficacy and mechanism of rifaximin in HSOS.

Methods

An HSOS model was established in mice through the administration of monocrotaline (MCT, 800 mg/kg), and part of the HSOS mice were intragastrically administered with rifaximin. Then, the efficacy of rifaximin in HSOS was evaluated based on the liver pathological findings, liver proinflammatory cytokines, and alanine aminotransferase and aspartate aminotransferase levels. The Ussing chamber was used to evaluate the intestinal permeability, and tight junction (TJ) proteins were measured by Western blotting and real-time polymerase chain reaction to evaluate the intestinal barrier integrity. Then, the serum proinflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay. Afterwards, an in vitro experiment was performed to determine the relationship between rifaximin and TJ proteins.

Results

Rifaximin effectively alleviated the MCT-induced HSOS liver injury, suppressed the expression of liver proinflammatory cytokines, and reduced the serum levels of tumor necrosis factor-alpha and interleukin-6. Furthermore, rifaximin reduced the intestinal permeability, improved the intestinal barrier integrity, and promoted the expression of TJ proteins.

Conclusion

The results revealed that the intestinal barrier integrity was destroyed in MCT-induced HSOS. The significant alleviation of MCT-induced HSOS induced by rifaximin might be correlated to the repairment of intestinal barrier integrity via the regulation of the TJ protein expression.

Keywords

rifaximin / hepatic sinusoidal obstruction syndrome / intestinal barrier / tight junction proteins / inflammation

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