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Promotion of mitochondrial energy metabolism during hepatocyte apoptosis in a rat model of acute liver failure.

Chen LY, Yang B, Zhou L, Ren F, Duan ZP, Ma YJ - Mol Med Rep (2015)

Bottom Line: Hepatocyte necrosis appeared at 12 h and was significantly higher at 24 h with inflammatory cell invasion.Therefore, these results demonstrated that energy metabolism is important in hepatocyte apoptosis during ALF and hepatocyte apoptosis is an active and energy‑consuming procedure.The current study on how hepatocyte energy metabolism affects the transmission of death signals may provide a basis for the early diagnosis and development of an improved therapeutic strategy for ALF.

View Article: PubMed Central - PubMed

Affiliation: The Second Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.

ABSTRACT
Hepatocyte apoptosis and energy metabolism in mitochondria have an important role in the mechanism of acute liver failure (ALF). However, data on the association between apoptosis and the energy metabolism of hepatocytes are lacking. The current study assessed the activity of several key enzymes in mitochondria during ALF, including citrate synthase (CS), carnitine palmitoyltransferase‑1 (CPT‑1) and cytochrome c oxidase (COX), which are involved in hepatocyte energy metabolism. A total of 40 male Sprague‑Dawley rats were divided into five groups and administered D‑galactosamine and lipopolysaccharide to induce ALF. Hepatic pathology and terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling examinations indicated that hepatocyte apoptosis was observed at 4 h and increased 8 h after ALF. Hepatocyte necrosis appeared at 12 h and was significantly higher at 24 h with inflammatory cell invasion. The results measured by electron microscopy indicated that ultrastructural changes in mitochondria began at 4 h and the mitochondrial outer membrane was completely disrupted at 24 h resulting in mitochondrial collapse. The expression of CS, CPT‑1 and COX was measured and analyzed using assay kits. The activity and protein expression of CS, CPT‑1 and COX began to increase at 4 h, reached a peak at 8 h and decreased at 12 h during ALF. The activities of CS, CPT‑1 and COX were enhanced during hepatocyte apoptosis suggesting that these enzymes are involved in the initiation and development of ALF. Therefore, these results demonstrated that energy metabolism is important in hepatocyte apoptosis during ALF and hepatocyte apoptosis is an active and energy‑consuming procedure. The current study on how hepatocyte energy metabolism affects the transmission of death signals may provide a basis for the early diagnosis and development of an improved therapeutic strategy for ALF.

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Histological examination of acute liver damage induced by D-galactosamine/lipopolysaccharide treatment in rats. Liver sections were stained with hematoxylin and eosin. ALF 4 h, hepatic tissue underwent ballooning degeneration without inflammatory invasion in the sinusoids; ALF 8 h, hepatocyte apoptosis and partial hyperemia was visible in the sinusoids and piecemeal necrosis and inflammatory invasion was observed; ALF 12 h, a large quantity of hepatocytes underwent piecemeal necrosis and there was rupture of hepatic cords; ALF 24 h, marked necrosis of hepatocytes and severe hyperemia was observed in the sinusoids, the boundary of hepatocytes became obscure, the fiber mesh scaffold collapsed and there was clear inflammatory invasion. ALF, acute liver failure.
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f1-mmr-12-04-5035: Histological examination of acute liver damage induced by D-galactosamine/lipopolysaccharide treatment in rats. Liver sections were stained with hematoxylin and eosin. ALF 4 h, hepatic tissue underwent ballooning degeneration without inflammatory invasion in the sinusoids; ALF 8 h, hepatocyte apoptosis and partial hyperemia was visible in the sinusoids and piecemeal necrosis and inflammatory invasion was observed; ALF 12 h, a large quantity of hepatocytes underwent piecemeal necrosis and there was rupture of hepatic cords; ALF 24 h, marked necrosis of hepatocytes and severe hyperemia was observed in the sinusoids, the boundary of hepatocytes became obscure, the fiber mesh scaffold collapsed and there was clear inflammatory invasion. ALF, acute liver failure.

Mentions: Histological examination revealed that the livers from control group animals demonstrated complete hepatic lobules without degeneration or necrosis by H&E staining. At ALF 4 h, hepatic tissue underwent ballooning degeneration without clear inflammatory invasion in the sinusoids. At ALF 8 h, there was apparent hepatocyte apoptosis, partial hyperemia in the sinusoids, piecemeal necrosis and inflammatory invasion. At ALF 12 h, a large quantity of hepatocytes underwent piecemeal necrosis and there was rupture of hepatic cords. At ALF 24 h, there was marked necrosis of hepatocytes and severe hyperemia in the sinusoids, the boundary of hepatocytes became obscure, the fiber mesh scaffold collapsed and there was clear inflammatory cell invasion (Fig. 1).


Promotion of mitochondrial energy metabolism during hepatocyte apoptosis in a rat model of acute liver failure.

Chen LY, Yang B, Zhou L, Ren F, Duan ZP, Ma YJ - Mol Med Rep (2015)

Histological examination of acute liver damage induced by D-galactosamine/lipopolysaccharide treatment in rats. Liver sections were stained with hematoxylin and eosin. ALF 4 h, hepatic tissue underwent ballooning degeneration without inflammatory invasion in the sinusoids; ALF 8 h, hepatocyte apoptosis and partial hyperemia was visible in the sinusoids and piecemeal necrosis and inflammatory invasion was observed; ALF 12 h, a large quantity of hepatocytes underwent piecemeal necrosis and there was rupture of hepatic cords; ALF 24 h, marked necrosis of hepatocytes and severe hyperemia was observed in the sinusoids, the boundary of hepatocytes became obscure, the fiber mesh scaffold collapsed and there was clear inflammatory invasion. ALF, acute liver failure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581801&req=5

f1-mmr-12-04-5035: Histological examination of acute liver damage induced by D-galactosamine/lipopolysaccharide treatment in rats. Liver sections were stained with hematoxylin and eosin. ALF 4 h, hepatic tissue underwent ballooning degeneration without inflammatory invasion in the sinusoids; ALF 8 h, hepatocyte apoptosis and partial hyperemia was visible in the sinusoids and piecemeal necrosis and inflammatory invasion was observed; ALF 12 h, a large quantity of hepatocytes underwent piecemeal necrosis and there was rupture of hepatic cords; ALF 24 h, marked necrosis of hepatocytes and severe hyperemia was observed in the sinusoids, the boundary of hepatocytes became obscure, the fiber mesh scaffold collapsed and there was clear inflammatory invasion. ALF, acute liver failure.
Mentions: Histological examination revealed that the livers from control group animals demonstrated complete hepatic lobules without degeneration or necrosis by H&E staining. At ALF 4 h, hepatic tissue underwent ballooning degeneration without clear inflammatory invasion in the sinusoids. At ALF 8 h, there was apparent hepatocyte apoptosis, partial hyperemia in the sinusoids, piecemeal necrosis and inflammatory invasion. At ALF 12 h, a large quantity of hepatocytes underwent piecemeal necrosis and there was rupture of hepatic cords. At ALF 24 h, there was marked necrosis of hepatocytes and severe hyperemia in the sinusoids, the boundary of hepatocytes became obscure, the fiber mesh scaffold collapsed and there was clear inflammatory cell invasion (Fig. 1).

Bottom Line: Hepatocyte necrosis appeared at 12 h and was significantly higher at 24 h with inflammatory cell invasion.Therefore, these results demonstrated that energy metabolism is important in hepatocyte apoptosis during ALF and hepatocyte apoptosis is an active and energy‑consuming procedure.The current study on how hepatocyte energy metabolism affects the transmission of death signals may provide a basis for the early diagnosis and development of an improved therapeutic strategy for ALF.

View Article: PubMed Central - PubMed

Affiliation: The Second Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.

ABSTRACT
Hepatocyte apoptosis and energy metabolism in mitochondria have an important role in the mechanism of acute liver failure (ALF). However, data on the association between apoptosis and the energy metabolism of hepatocytes are lacking. The current study assessed the activity of several key enzymes in mitochondria during ALF, including citrate synthase (CS), carnitine palmitoyltransferase‑1 (CPT‑1) and cytochrome c oxidase (COX), which are involved in hepatocyte energy metabolism. A total of 40 male Sprague‑Dawley rats were divided into five groups and administered D‑galactosamine and lipopolysaccharide to induce ALF. Hepatic pathology and terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling examinations indicated that hepatocyte apoptosis was observed at 4 h and increased 8 h after ALF. Hepatocyte necrosis appeared at 12 h and was significantly higher at 24 h with inflammatory cell invasion. The results measured by electron microscopy indicated that ultrastructural changes in mitochondria began at 4 h and the mitochondrial outer membrane was completely disrupted at 24 h resulting in mitochondrial collapse. The expression of CS, CPT‑1 and COX was measured and analyzed using assay kits. The activity and protein expression of CS, CPT‑1 and COX began to increase at 4 h, reached a peak at 8 h and decreased at 12 h during ALF. The activities of CS, CPT‑1 and COX were enhanced during hepatocyte apoptosis suggesting that these enzymes are involved in the initiation and development of ALF. Therefore, these results demonstrated that energy metabolism is important in hepatocyte apoptosis during ALF and hepatocyte apoptosis is an active and energy‑consuming procedure. The current study on how hepatocyte energy metabolism affects the transmission of death signals may provide a basis for the early diagnosis and development of an improved therapeutic strategy for ALF.

Show MeSH
Related in: MedlinePlus