Effects of Kupffer cell inhibition on liver function and hepatocellular activity in mice.

Published on Oct 1, 2003in International Journal of Molecular Medicine3.098
· DOI :10.3892/IJMM.12.4.549
Hong Ding1
Estimated H-index: 1
(WHU: Wuhan University),
Renxiu Peng1
Estimated H-index: 1
+ 1 AuthorsQingdi Q. Li18
Estimated H-index: 18
Kupffer cells are the tissue macrophages in the liver and play an important role in the defense mechanisms of the body. However, their role in liver function and hepatocellular activity remains unclear. This study was therefore undertaken to investigate the effect of gadolinium chloride-induced Kupffer cell dysfunction on liver function and hepatocellular signaling activity in mice and to establish an animal model for studying the role of Kupffer cells in vivo. Kunming mice were intraperitoneally injected with different doses of gadolinium chloride (GdCl 3 ), a selective inhibitor of Kupffer cells, and the mice were sacrificed at different time periods following the drug administration. Hepatotoxicity and Kupffer cell function, as well as the levels of signaling molecules and inflammatory mediators in liver tissue, were measured. We demonstrated that the administration of 10-20 mg/kg GdCl 3 caused apoptosis of Kupffer cells and blocked the Kupffer cell effector function, as shown by a decrease in CD68 expression and phagocytic activity. In addition, the NO, PGE 2 and cAMP levels in the liver were also reduced significantly. Furthermore, 20 mg/kg GdCl 3 decreased the levels of cNOS, PKC and NF-KB p65 expression by 26.6, 68 and 64%, respectively. In contrast, hepatotoxicity was not observed when the same doses of GdCl 3 were used. Moreover, we found that Kupffer cell function and the NO, PGE 2 and cAMP contents, as well as PKC and NF-κB p65 levels in the liver were only partially, but not fully recovered in up to six days following 20 mg/kg GdCl 3 injection. However, the administration of higher doses of GdCl 3 (40 mg/kg) caused both hepatotoxicity and Kupffer cell necrosis, as well as an increased release of TNF, NO, and PGE 2 in the liver. These results indicate that administration of suitable doses of GdCl 3 blocked the effector function of Kupffer cells selectively, but did not cause liver parenchymal cell toxicity, and provide a frame-work for the establishment of an animal model for studying the role of Kupffer cells in signaling in the liver. Lastly, the present study also provides evidence that shows there is a positive association between the expression of cAMP, PKC, or NF-KB and the levels of NO, PGE 2 and TNF in the liver of Kupffer-cell-blocked mice, and suggests that Kupffer cells may play a part in mediating liver function and hepatocellular activity.
📖 Papers frequently viewed together
94 Citations
73 Citations
81 Citations
Cited By21
Last. Ming Hong (Guangzhou University of Chinese Medicine)
view all 7 authors...
Previous epidemiological and histopathological studies have demonstrated that long-term computation of Kweichow Moutai liquor (Moutai) could induce fatty liver disease but few of these patients with fatty liver will develop hepatic fibrosis or cirrhosis. Moutai liquor has a different brewing technique from other white wine, which may generate various microorganisms in the unique geographical conditions and may produce plenty of vitamins, amino acids, and several essential microelements. In the c...
#1Yang Tian (ZJU: Zhejiang University)H-Index: 5
#2Jingcheng Wang (ZJU: Zhejiang University)H-Index: 4
Last. Shusen Zheng (ZJU: Zhejiang University)H-Index: 64
view all 10 authors...
Background Liver transplantation is the optimal treatment option for end-stage liver disease, but organ shortages dramatically restrict its application. Donation after cardiac death (DCD) is an alternative approach that may expand the donor pool, but it faces challenges such as graft dysfunction, early graft loss, and cholangiopathy. Moreover, DCD liver grafts are no longer eligible for transplantation after their warm ischaemic time exceeds 30 min. Mesenchymal stem cells (MSCs) have been propos...
23 CitationsSource
#1Jiazheng Li (Aichi Medical University)H-Index: 3
#2Nobuhisa Kandatsu (Aichi Medical University)H-Index: 8
Last. Yoshihiro Fujiwara (Aichi Medical University)H-Index: 15
view all 8 authors...
Purpose The present study, conducted in rats, investigated whether propofol attenuates lipopolysaccharide (LPS)-triggered liver dysfunction via regulation of tumor necrosis factor (TNF)-α production in activated Kupffer cells.
5 CitationsSource
#1Kenya Murase (Osaka University)H-Index: 45
#2Purapan Assanai (Osaka University)H-Index: 2
Last. Motoko Nishiura (Osaka University)H-Index: 4
view all 6 authors...
Abstract The purpose of this study was to develop a method for analyzing the kinetic behavior of superparamagnetic iron oxide nanoparticles (SPIONs) in the murine liver under control of body temperature using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) and an empirical mathematical model (EMM). First, we investigated the influence of body temperature on the kinetic behavior of SPIONs in the liver by controlling body temperature using our temperature-control system. Secon...
3 CitationsSource
#1Xi YangH-Index: 22
#3Qiang ShiH-Index: 20
Last. William F. SalminenH-Index: 17
view all 4 authors...
The liver is the largest internal organ in the human body and it is the main site for the metabolism of endogenous molecules and xenobiotics. Drug-induced liver injury is one of the leading causes of drug attrition during drug development and post-marketing drug withdrawal. Current biomarkers can detect liver injury but there are many inadequacies that make them less than ideal. For example, the serum level of alanine aminotransferase (ALT) is the most commonly used biomarker of hepatocellular i...
22 CitationsSource
Objective Hepatic signal recovery, rather than reduction, in ferucarbotran-enhanced magnetic resonance imaging (MRI) is a potential diagnostic marker of liver damage. We investigated hepatic signal recovery in rats with gadolinium chloride (GdCl3)-induced Kupffer cell (KC) damage.
5 CitationsSource
#1Xi YangH-Index: 22
#2William F. SalminenH-Index: 17
Drug-induced liver injury (DILI) is of great concern to human health. Generally, liver function and injury is evaluated based upon clinical signs, a select group of serum clinical biomarkers, and occasionally liver biopsies. While alanine aminotransferase, the most commonly used biomarker of hepatocellular injury, is a sensitive marker of liver injury, it is not necessarily specific for liver injury. Furthermore, alanine aminotransferase levels may not always correlate with the extent of injury....
20 CitationsSource
#1T.A. KorolenkoH-Index: 1
#2O.A. LevinaH-Index: 1
Last. N.G. SavchenkoH-Index: 1
view all 4 authors...
Cholestasis, caused by the interrupted excretion of bile, resulting in an accumulation of bile products in the body fluids is characteristic of many human liver diseases (Sherlock & Dooley, 1997). Experimental animal models of cholestasis allow the understanding of pathophysiological mechanisms involved and their clinical correlates (Chang et al., 2005; Chandra & Brower, 2004). The most common experimental models of intrahepatic cholestasis are estrogen-induced, endotoxin-induced and drug-induce...
1 CitationsSource
Context: Tournefortia sarmentosa Lam. (Boraginaceae), a Chinese herbal medicine, is commonly used as a detoxicant or anti-inflammatory agent.Objective: As acetaminophen (APAP) is a well-known hepatotoxin, we investigated the effect of the aqueous extract of the T. sarmentosa on APAP-induced hepatotoxicity in vivo and in vitro.Materials and methods: Levels of liver function markers serum glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), and alkaline phosphatase (...
9 CitationsSource
#1Szabolcs Ábrahám (University of Szeged)H-Index: 8
#2Edit Hermesz (University of Szeged)H-Index: 18
Last. György Lázár (University of Szeged)H-Index: 19
view all 8 authors...
Abstract Aims Heme oxygenase (HO) and metallothionein (MT) genes are rapidly upregulated in the liver by pro-inflammatory cytokines and/or endotoxin as protection against cellular stress and inflammation. Gadolinium chloride (GdCl3)-induced Kupffer cell blockade has beneficial consequences in endotoxemia following bile duct ligation. Herein we further characterized the effects of Kupffer cell inhibition on the activation of the antioxidant defense system (HO and MT gene expressions, and antioxid...
5 CitationsSource