Open Access Research Article Yoshino et al., Vasc Med Surg 2015, 3:2 DOI: 10.4172/2329-6925.1000194 Volume 3 • Issue 2 • 1000194 J Vasc Med Surg ISSN: 2329-6925 JVMS, an open access journal *Corresponding author: Taro Mizutani, Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki- 305-8575, Japan, Tel: +81-29-853- 3210, 3081; Fax: +81-29-853-5984; E-mail: mizutani@md.tsukuba.ac.jp Received January 24, 2015; Accepted March 14, 2015; Published March 16, 2015 Citation: Yoshino Y, Jesmin S, Islam M, Shimojo N, Sakuramoto H, et al. (2015) Landiolol Hydrochloride Ameliorates Liver Injury in a Rat Sepsis Model by Down Regulating Hepatic TNF-Α. J Vasc Med Surg 3: 194. doi:10.4172/2329- 6925.1000194 Copyright: © 2015 Yoshino Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Landiolol Hydrochloride Ameliorates Liver Injury in a Rat Sepsis Model by Down Regulating Hepatic TNF-Α Yasuyo Yoshino, Subrina Jesmin, Majedul Islam, Nobutake Shimojo, Hideaki Sakuramoto, Masami Oki, Tanzila Khatun, Masato Suda, Satoru Kawano and Taro Mizutani* Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan Keywords: Landiolol hydrochloride; Liver injury; TNF-α; Endothelin-1; Sepsis; Rat model Introduction 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]. Te liver is one of the organs that are normally damaged during the pathogenesis of sepsis and septic shock. Terefore, protecting the liver [2-4] is an important target in sepsis treatment and management. Although numerous studies on infection- or sepsis- induced liver injury have been conducted [5,6], to date no efective treatment has been reported on this disorder. We know that during sepsis, liver functions are altered by the activation of infammatory processes [6,7] to date no efective treatment has been reported on this disorder. We know that during sepsis, liver functions are altered by the activation of infammatory processes. For instance, 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 Kupfer cells [8,9]. Specifcally, LPS stimulates Kupfer 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]. Endothelin-1 (ET-1), a potent vasoconstrictor with vasoproliferative activity, is believed to participate in the pathogenesis of sepsis, and its plasma (ET-1) levels signifcantly increase [11] in sepsis. Te possible involvement of the ET system in human septic shock is further supported by a clear correlation between endothelin plasma levels and morbidity and mortality in septic patients [12,13]. Infusion of ET-1 in human causes cardiovascular changes, in part resembling those seen 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 infammatory 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 signifcantly 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 signifcantly increased. In addition, at 3 h after LPS administration signifcant 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 fndings, it can be stated that landiolol may exert protective effects on liver injury in septic rats by normalizing local expression levels of infammatory cytokine, such as TNF-α. during sepsis i.e. decreased cardiac output and vasoconstriction in the pulmonary, renal and splanchnic circulation [13]. In our previous study, we clearly demonstrated that ET-1 is upregulated in liver during sepsis in a time-dependent manner [14]. Landiolol, an ultra-short-acting and highly cardio-selective β-1 blocker, has become useful for various medical problems in recent days, as evidenced from both clinical and animal studies. Recent studies have demonstrated that co-treatment of LPS with landiolol protects against acute lung injury and cardiac dysfunction in a rat model of LPS-induced systemic infammation, which was also associated with a signifcant reduction in serum levels of the infammation mediator HMGB-1 and histological lung damage [15]. More recently, our group has demonstrated that landiolol treatment signifcantly normalized various components of altered cardiac ET-1 signaling system in septic rat [16]. In addition, Ogura et al. reported the reno-protective efects of landiolol hydrochloride during sepsis by normalizing the altered expression of ET-1 and HIF-l alpha levels [17]. However, no study has Journal of Vascular Medicine & Surgery J ou r n a l o f V a s c u l a r M e d i c i n e & S u r g e r y ISSN: 2329-6925