ABSTRACT
BACKGROUND: Endotoxemia may occur after hepatectomy and become the cause of post-operative death. Fibronectins (Fns) are involved in a number of biological processes, such as cellular adhesion, motility, differentiation, apoptosis, hemostasis, wound healing, and ischemic injury. Studies were performed to determine whether Fn influences the survival rate of rats subjected to endotoxin-induced liver injury after partial hepatectomy. MATERIALS AND METHODS: Lipopolysaccharide (LPS) was administered intravenously to male Sprague-Dawley rats within 48 h of 70% hepatectomy. Before LPS administration, plasma Fn or bovine serum albumin was given intravenously. RESULTS: The survival rate of the Fn-treated group was markedly improved compared with that of the controls. Fn prevented increases in the concentrations of serum enzymes and total bilirubin related to liver injury. The levels of inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1beta, and cytokine-induced neutrophil chemoattractant, in serum and liver tissue, also were significantly lower in the Fn-treated group than in the control group. Furthermore, the degree of apoptosis and necrosis in remnant liver was significantly decreased in the Fn-treated rats compared with the controls. CONCLUSIONS: These results indicate that Fn prevents endotoxin-induced liver injury after partial hepatectomy, at least in part through the inhibition of production of inflammatory cytokines, necrosis and apoptosis in the remaining liver.
Subject(s)
Extracellular Matrix Proteins/therapeutic use , Fibronectins/therapeutic use , Hepatectomy/adverse effects , Lipopolysaccharides/adverse effects , Liver Diseases/prevention & control , Liver/pathology , Animals , Apoptosis/physiology , Cytokines/analysis , Endotoxemia/microbiology , Endotoxins/adverse effects , Extracellular Matrix Proteins/pharmacology , Fibronectins/pharmacology , Liver/blood supply , Liver/drug effects , Liver/physiopathology , Liver Diseases/microbiology , Male , Models, Animal , Necrosis , Rats , Rats, Sprague-Dawley , Survival AnalysisABSTRACT
BACKGROUND/AIMS: Massive liver resection causes a variety of complications including endotoxemia. Pirfenidone (PFD) is a new experimental drug used as antifibrotic agent. Studies were performed to investigate whether PFD influences the survival rate of animals with endotoxin-induced liver injury after partial hepatectomy, and the mechanisms involved. METHODS: Rats were treated with lipopolysaccharide (LPS) 48 h after 70% hepatectomy. PFD was administered orally before LPS injection. RESULTS: PFD improved the survival rate of LPS-treated rats after hepatectomy. PFD prevented increases in serum enzymes and total bilirubin related to liver injury. Histopathological analysis revealed that PFD inhibited the enhancement in hepatic necrosis and apoptosis. Further, PFD inhibited increases of inflammatory cytokines and cytokine-induced neutrophil chemoattractant (CINC) in serum and liver, followed by decreases of number of infiltrating neutrophils into liver. Electrophoretic mobility shift assay revealed that PFD inhibited the activation of transcription factor nuclear factor-kappa B (NF-kappa B) induced by LPS. PFD also reduced the induction of inducible nitric oxide synthase (iNOS) in the liver of LPS-treated rats. CONCLUSIONS: These results indicate that PFD inhibits the productions of inflammatory cytokines, CINC and iNOS in part through the inhibition of NF-kappa B activation, resulting in the prevention of endotoxin-induced liver injury after hepatectomy.
Subject(s)
Endotoxemia/complications , Hepatectomy/adverse effects , Hepatectomy/methods , Liver Diseases/etiology , Liver Diseases/prevention & control , Pyridones/pharmacology , Animals , Chemokines, CXC/antagonists & inhibitors , Cytokines/antagonists & inhibitors , Inflammation Mediators/antagonists & inhibitors , Intercellular Signaling Peptides and Proteins , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , NF-kappa B/antagonists & inhibitors , Necrosis , Neutrophil Infiltration/drug effects , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase Type II , Rats , Rats, Sprague-Dawley , Survival Rate , Transcription Factors/antagonists & inhibitorsABSTRACT
The biological effects of far-infrared ray (FIR) on whole organisms remain poorly understood. The aim of our study was to investigate not only the hyperthermic effect of the FIR irradiation, but also the biological effects of FIR on wound healing. To evaluate the effect of FIR on a skin wound site, the speed of full-thickness skin wound healing was compared among groups with and without FIR using a rat model. We measured the skin wound area, skin blood flow, and skin temperature before and during FIR irradiation, and we performed histological inspection. Wound healing was significantly more rapid with than without FIR. Skin blood flow and skin temperature did not change significantly before or during FIR irradiation. Histological findings revealed greater collagen regeneration and infiltration of fibroblasts that expressed transforming growth factor-beta1 (TGF-beta1) in wounds in the FIR group than in the group without FIR. Stimulation of the secretion of TGF-beta1 or the activation of fibroblasts may be considered as a possible mechanisms for the promotive effect of FIR on wound healing independent of skin blood flow and skin temperature.
