Central nervous system and systemic oxidative stress interplay with inflammation in a bile duct ligation rat model of type C hepatic encephalopathy

In cholestatic liver diseases, impaired bile excretion disrupts lipid homeostasis. We investigated changes of lipid metabolism, including mitochondrial β-oxidation, in a rat model of bile duct ligation (BDL) in which chorionic plate-derived mesenchymal stem cells (CP-MSCs) were transplanted. Serum cholesterol level, which was elevated after BDL, was significantly decreased following CP-MSC transplantation. The expression levels of genes involved in intracellular lipid uptake, including long-chain fatty acyl-CoA synthetases and fatty acid transport proteins, were decreased in rats after BDL; however, they were not significantly changed by subsequent CP-MSC transplantation. Carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme in mitochondrial β-oxidation, was upregulated after BDL and then was downregulated after CP-MSC transplantation. CPT1A expression was changed via microRNA-33—a posttranscriptional regulator of CPT1A—in a peroxisome proliferator-activated receptor α-independent manner. Cellular adenosine triphosphate production—an indicator of mitochondrial function—was reduced after BDL and was restored by CP-MSC transplantation. Expression levels of heme oxygenases also were significantly affected following BDL and CP-MSC transplantation. Lipid metabolism is altered in response to chronic cholestatic liver injury and can be restored by CP-MSC transplantation. Our study findings support the therapeutic potential of CP-MSCs in cholestatic liver diseases and help in understanding the fundamental mechanisms by which CP-MSCs affect energy metabolism.

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CIRRHOSIS INDUCES APOPTOSIS IN RENAL TISSUE THROUGH INTRACELLULAR OXIDATIVE STRESS

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032015000100014 ◽

2015 ◽

Vol 52 (1) ◽

pp. 65-71 ◽

Cited By ~ 5

Author(s):

Keli Cristina Simões da SILVEIRA ◽

Cassiana Macagnan VIAU ◽

Josiane Raskopf COLARES ◽

Jenifer SAFFI ◽

Norma Possa MARRONI ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Enzymes ◽

Membrane Potential ◽

Bile Duct ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Bile Duct Ligation ◽

Decompensated Cirrhosis ◽

Biliary Cirrhosis ◽

Duct Ligation

Background Renal failure is a frequent and serious complication in patients with decompensated cirrhosis. Objectives We aimed to evaluate the renal oxidative stress, cell damage and impaired cell function in animal model of cirrhosis. Methods Secondary biliary cirrhosis was induced in rats by ligation of the common bile duct. We measured TBARS, ROS and mitochondrial membrane potential in kidney as markers of oxidative stress, and activities of the antioxidant enzymes. Relative cell viability was determined by trypan blue dye-exclusion assay. Annexin V-PE was used with a vital dye, 7-AAD, to distinguish apoptotic from necrotic cells and comet assay was used for determined DNA integrity in single cells. Results In bile duct ligation animals there was significant increase in the kidney lipoperoxidation and an increase of the level of intracellular ROS. There was too an increase in the activity of all antioxidant enzymes evaluated in the kidney. The percentage viability was above 90% in the control group and in bile duct ligation was 64.66% and the dominant cell death type was apoptosis. DNA damage was observed in the bile duct ligation. There was a decreased in the mitochondrial membrane potential from 71.40% ± 6.35% to 34.48% ± 11.40% in bile duct ligation. Conclusions These results indicate that intracellular increase of ROS cause damage in the DNA and apoptosis getting worse the renal function in cirrhosis.

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