Landiolol Hydrochloride Ameliorates Liver Injury in a Rat Sepsis Model by Down Regulating Hepatic TNF-a

Yasuyo Yoshino Subrina Jesmin

doi:10.4172/2329-6925.1000194

Abstract

Aims: The effects of a beta blocker, especially an ultra-short acting selective beta blocker, such as landiolol hydrochloride on the organ protection in sepsis are unclear. The present study aimed to investigate whether acute (early hours) liver injury in a rat model of sepsis induced by lipopolysaccharide (LPS) administration: a) can be corrected by administering landiolol and b) whether landiolol’s effects on liver injury is accomplished by diminishing the elevated expression of inflammatory cytokine, such as tumor necrosis factor (TNF)-α and a vaso constrictor peptide, such as endothelin (ET)-1. Methods: Eight (8)-week-old male Wistar rats were administered for three hours with either LPS (n=12), or continuously with LPS plus landiolol (n=11). Control rats were treated with saline only in a similar manner as the treatment group during the relevant time points (n=13). Results: Following LPS administration, blood gas and hemodynamic parameters were significantly altered compared to control rats at 3 h. Also, At 3 h after LPS administration, circulatory levels of ALT, AST, TNF-α and ET-1 were significantly increased. In addition, at 3 h after LPS administration significant features of hepatic injuries at morphological levels were also evident. Co-treatment of rats with LPS and landiolol ameliorated hepatic injury at 3 h post-treatment, as well as reversed elevated circulatory levels of factors associated with liver injury back to normal levels, such as AST and ALT, and local hepatic levels of TNF-α. Conclusion: Based on the current findings, it can be stated that landiolol may exert protective effects on liver injury in septic rats by normalizing local expression levels of inflammatory cytokine, such as TNF-α.

Highlights

Sepsis, a critical medical emergency, is associated with tissue hypoperfusion and metabolic impairment, which may contribute to the subsequent development of multiple organ failure normally associated with this disorder [1]
Both ex-vivo and in-vitro studies have demonstrated that tumor necrosis factor-α (TNF-α) is released in response to lipopolysaccharide (LPS), primarily by Kupffer cells [8,9]
We investigated whether landiolol hydrochloride plays an important role in ameliorating liver injury during sepsis and whether such blockage involves attenuation of hepatic TNF-α and ET-1 expression

Summary

Introduction

A critical medical emergency, is associated with tissue hypoperfusion and metabolic impairment, which may contribute to the subsequent development of multiple organ failure normally associated with this disorder [1]. Numerous studies on infection- or sepsisinduced liver injury have been conducted [5,6], to date no effective treatment has been reported on this disorder. We know that during sepsis, liver functions are altered by the activation of inflammatory processes [6,7] to date no effective treatment has been reported on this disorder. We know that during sepsis, liver functions are altered by the activation of inflammatory processes. Both ex-vivo and in-vitro studies have demonstrated that tumor necrosis factor-α (TNF-α) is released in response to lipopolysaccharide (LPS), primarily by Kupffer cells [8,9]. LPS stimulates Kupffer cells to secrete TNF-α, which, subsequently, contributes to the pathogenesis of LPS-induced liver injury by a direct or an indirect polymorphonuclear leucocyte-dependent mechanism [9,10]

Methods

Results

Discussion

Conclusion