Suppression of lipopolysaccharide-induced nitric oxide synthase expression by platelet-activating factor receptor antagonists in the rat liver and cultured rat kupffer cells

Abstract

Excessive nitric oxide (NO) generated by hepatic cells in response to lipopolysaccharide (LPS) and inflammatory substances (e.g., platelet-activating factor [PAF]) is a key contributor to the pathophysiological outcomes observed in the liver during sepsis. In rats subjected to liver-focused endotoxemia, inducible nitric oxide synthase (iNOS) levels in the intact liver were elevated by 6 hours; cell-specific expression of iNOS messenger RNA (

Free radical scavenger (edaravone) prevents endotoxin-induced liver injury after partial hepatectomy in rats

“…In addition, during endotoxemia, Kupffer cells, resident macrophages of the liver, play an important role in the inflammatory immune response [7,8]. Kupffer cells activated by endotoxin release various inflammatory mediators including eicosanoids, inflammatory cytokines including tumor necrosis factor (TNF)-a, interleukin (IL)-1b, interferon (IFN)-g, cytokine-induced neutrophil chemoattractant (CINC), and free radicals [9][10][11][12]. These inflammatory mediators participate in the process of endotoxemia and liver injury, leading to MOF, individually or by forming a network [7,13,14].…”

Ischemia and hepatic reperfusion: Is it possible to reduce hepatic alterations?

“…The first is expressed in brain (nNOS) and endothelium (eNOS), while iNOS is especially present in the liver. 3,8,9 NO has some cytoprotective effect in hepatic I/R injury, 3,10,11 but also has cytotoxic effects. Peroxynitrite and superoxide are believed to be major contributors to cytotoxicity through nitration of tyrosine residues, apoptosis, and lipid peroxidation when produced by activated cells expressing iNOS.…”

Effect of a potent iNOS inhibitor (ONO-1714) on acetaminophen-induced hepatotoxicity in the rat

“…In contrast, neither hepatic necrosis nor abnormality was seen in the rat pretreated with ONO-1714 (B). (Vos et al, 1999), Kupffer cells (Mustafa et al, 1999) and endothelial cells (Laskin et al, 1994) produce NO that plays a dual role, being cytoprotective and cytotoxic (Li and Billiar, 1999;Laskin et al, 2001). The small amount of NO produced by endothelial NOS (eNOS) acts to maintain homeostasis and has a cytoprotective effect (Albrecht et al, 2003), whereas excessive NO formation by iNOS that is induced by cytokines (Nakayama et al, 1994) and LPS (Zhang et al, 2000) in hepatocytes or Kkupffer cells, exerts cytotoxic actions via lipid peroxidation (Shibuki et al, 2000), activation of poly(ADP-ribose) polymerase (Khandoga et al, 2002), apoptosis (Lin et al, 1999;Zhuang and Simon, 2000) and nitration of tyrosine residues (Haddad et al, 1994;Demiryurek et al, 2000).…”