GdCl3 abates hepatic ischemia-reperfusion injury by inhibiting apoptosis in rats. 2009

Jian-Yi Li, and Xi Gu, and Wen-Hai Zhang, and Shi Jia, and Yong Zhou
Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, China.

BACKGROUND Gadolinium chloride (GdCl(3)) is a specific inhibitor of Kupffer cells (KCs), which are important promoters of various liver injuries. It is therefore of interest to explore the role of KCs in liver ischemia-reperfusion injury and their relations with apoptosis caused by ischemia-reperfusion injury. METHODS One hundred male Wistar rats (190-210 g, 6-7 weeks old) were divided into two groups at random, GdCl(3) group and control group. Samples were collected at 0.5, 1, 6, 12, and 24 hours from each group after reperfusion. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by an automatic biochemical analyzer. TNF-alpha in serum was measured by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA) in the liver mitochondria was measured by a colorimetric method. Pathological changes in the liver and immunohistochemical staining for caspase-3 were observed under an optical microscope. The ratio of apoptotic cells was measured by TdT-mediated dUTP nick-end labeling (TUNEL), and ultrastructural features of apoptosis were observed with a transmission electron microscope (TEM). RESULTS The levels of ALT in the GdCl(3) group were lower than those in the control group after reperfusion for 0.5, 1, 6 and 12 hours (P<0.05); and the levels of AST in the GdCl(3) group were lower than those in the control group after reperfusion for 6 and 12 hours (P<0.05). The levels of TNF-alpha in the GdCl(3) group were lower than those in the control group after reperfusion for each time (P<0.05). The concentrations of MDA after reperfusion in the GdCl(3) group were lower than those in the control group after reperfusion for 6, 12 and 24 hours (P<0.05). After reperfusion for 0.5, 1, 6 and 12 hours, the integral optical density (IOD) of caspase-3-positive cells was lower in the GdCl(3) group than in the control group (P<0.05). After reperfusion for 1, 6, and 12 hours, the IOD of cells stained by TUNEL in the GdCl(3) group was lower than that in the control group (P<0.05). CONCLUSIONS GdCl(3) inhibits the activity of ALT, AST and TNF-alpha, decreases the accumulation of MDA in mitochondria, and depresses the expression of caspase-3 in liver after ischemia-reperfusion. This may be an important protective mechanism by depressing KCs and indirectly inhibiting liver cell apoptosis.

UI MeSH Term Description Entries
D007728 Kupffer Cells Specialized phagocytic cells of the MONONUCLEAR PHAGOCYTE SYSTEM found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood and dispose of worn out red blood cells. Kupffer Cell,Cell, Kupffer,Cells, Kupffer
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008315 Malondialdehyde The dialdehyde of malonic acid. Malonaldehyde,Propanedial,Malonylaldehyde,Malonyldialdehyde,Sodium Malondialdehyde,Malondialdehyde, Sodium
D008930 Mitochondria, Liver Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4) Liver Mitochondria,Liver Mitochondrion,Mitochondrion, Liver
D005682 Gadolinium An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors.
D000410 Alanine Transaminase An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2. Alanine Aminotransferase,Glutamic-Pyruvic Transaminase,SGPT,Alanine-2-Oxoglutarate Aminotransferase,Glutamic-Alanine Transaminase,Alanine 2 Oxoglutarate Aminotransferase,Aminotransferase, Alanine,Aminotransferase, Alanine-2-Oxoglutarate,Glutamic Alanine Transaminase,Glutamic Pyruvic Transaminase,Transaminase, Alanine,Transaminase, Glutamic-Alanine,Transaminase, Glutamic-Pyruvic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000893 Anti-Inflammatory Agents Substances that reduce or suppress INFLAMMATION. Anti-Inflammatory Agent,Antiinflammatory Agent,Agents, Anti-Inflammatory,Agents, Antiinflammatory,Anti-Inflammatories,Antiinflammatories,Antiinflammatory Agents,Agent, Anti-Inflammatory,Agent, Antiinflammatory,Agents, Anti Inflammatory,Anti Inflammatories,Anti Inflammatory Agent,Anti Inflammatory Agents
D001219 Aspartate Aminotransferases Enzymes of the transferase class that catalyze the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 2.6.1.1. Aspartate Aminotransferase,Aspartate Transaminase,Glutamic-Oxaloacetic Transaminase,SGOT,Aspartate Apoaminotransferase,Glutamate-Aspartate Transaminase,L-Aspartate-2-Oxoglutarate Aminotransferase,Serum Glutamic-Oxaloacetic Transaminase,Aminotransferase, Aspartate,Aminotransferase, L-Aspartate-2-Oxoglutarate,Aminotransferases, Aspartate,Apoaminotransferase, Aspartate,Glutamate Aspartate Transaminase,Glutamic Oxaloacetic Transaminase,Glutamic-Oxaloacetic Transaminase, Serum,L Aspartate 2 Oxoglutarate Aminotransferase,Serum Glutamic Oxaloacetic Transaminase,Transaminase, Aspartate,Transaminase, Glutamate-Aspartate,Transaminase, Glutamic-Oxaloacetic,Transaminase, Serum Glutamic-Oxaloacetic

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