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Abstrakt
Landiolol Hydrochloride Ameliorates Liver Injury in a Rat Sepsis Model by Down Regulating Hepatic TNF-A
Yasuyo Yoshino, Subrina Jesmin, Majedul Islam, Nobutake Shimojo, Takeshi Yamada, Hideaki Sakuramoto, Masami Oki, Tanzila Khatun, Masato Suda, Satoru Kawano and Taro Mizutani
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.