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Hepatocyte apoptosis is enhanced after ischemia/reperfusion in the steatotic liver.

Suzuki T, Yoshidome H, Kimura F, Shimizu H, Ohtsuka M, Takeuchi D, Kato A, Furukawa K, Yoshitomi H, Iida A, Dochi T, Miyazaki M - J Clin Biochem Nutr (2011)

Bottom Line: Liver steatosis is associated with organ dysfunction after hepatic resection and transplantation which may be caused by hepatic ischemia/reperfusion injury.In mice treated with aminoguanidine, ischemia/reperfusion-induced increases in serum alanine aminotransferase levels and apoptosis were significantly reduced in steatotic liver compared with mice treated with phosphate buffered saline.Survival of mice with steatotic livers significantly improved by treatment with aminoguanidine.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana Chuo-ku, Chiba 260-0856, Japan.

ABSTRACT
Liver steatosis is associated with organ dysfunction after hepatic resection and transplantation which may be caused by hepatic ischemia/reperfusion injury. The aim of the current study was to determine the precise mechanism leading to hepatocyte apoptosis after steatotic liver ischemia/reperfusion. Using a murine model of partial hepatic ischemia for 90 min, we examined the levels and pathway of apoptosis, and the peroxynitrite expression, serum alanine aminotransferase levels, and liver histology 1 and 4 h after reperfusion. In the steatotic liver, the peroxynitrite expression increased after ischemia/reperfusion. Significant hepatocyte apoptosis in the steatotic liver was seen after reperfusion, caused by upregulation of cleaved caspases 9 and 3, but not caspase 8. Serum alanine aminotransferase levels were elevated and histological examination revealed severe liver injury in the steatotic liver 4 h after reperfusion. In mice treated with aminoguanidine, ischemia/reperfusion-induced increases in serum alanine aminotransferase levels and apoptosis were significantly reduced in steatotic liver compared with mice treated with phosphate buffered saline. Survival of mice with steatotic livers significantly improved by treatment with aminoguanidine. Our data suggested that the steatotic liver is vulnerable to hepatic ischemia/reperfusion, leading to significant hepatocyte apoptosis by the mitochondrial permeability transition, and thereby resulting in organ dysfunction.

No MeSH data available.


Related in: MedlinePlus

NF-κB activation in whole liver homogenates during hepatic ischemia/reperfusion. Nuclear extracts from liver tissue were subjected to EMSA. The results are representative of two separate time-course experiments. Both WT and FL mice underwent either a sham operation or ischemia for 90 min (I/R).
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Figure 3: NF-κB activation in whole liver homogenates during hepatic ischemia/reperfusion. Nuclear extracts from liver tissue were subjected to EMSA. The results are representative of two separate time-course experiments. Both WT and FL mice underwent either a sham operation or ischemia for 90 min (I/R).

Mentions: Since NF-κB is known to play a role in both inflammatory responses and anti-apoptosis effects,(11–24) we performed EMSA to determine whether NF-κB activation was induced by hepatic ischemia/reperfusion. After reperfusion, nuclear translocation of NF-κB in WT mice increased 1 and 4 h after reperfusion, but little NF-κB activation was observed in FL mice up to 4 h after reperfusion (Fig. 3).


Hepatocyte apoptosis is enhanced after ischemia/reperfusion in the steatotic liver.

Suzuki T, Yoshidome H, Kimura F, Shimizu H, Ohtsuka M, Takeuchi D, Kato A, Furukawa K, Yoshitomi H, Iida A, Dochi T, Miyazaki M - J Clin Biochem Nutr (2011)

NF-κB activation in whole liver homogenates during hepatic ischemia/reperfusion. Nuclear extracts from liver tissue were subjected to EMSA. The results are representative of two separate time-course experiments. Both WT and FL mice underwent either a sham operation or ischemia for 90 min (I/R).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045687&req=5

Figure 3: NF-κB activation in whole liver homogenates during hepatic ischemia/reperfusion. Nuclear extracts from liver tissue were subjected to EMSA. The results are representative of two separate time-course experiments. Both WT and FL mice underwent either a sham operation or ischemia for 90 min (I/R).
Mentions: Since NF-κB is known to play a role in both inflammatory responses and anti-apoptosis effects,(11–24) we performed EMSA to determine whether NF-κB activation was induced by hepatic ischemia/reperfusion. After reperfusion, nuclear translocation of NF-κB in WT mice increased 1 and 4 h after reperfusion, but little NF-κB activation was observed in FL mice up to 4 h after reperfusion (Fig. 3).

Bottom Line: Liver steatosis is associated with organ dysfunction after hepatic resection and transplantation which may be caused by hepatic ischemia/reperfusion injury.In mice treated with aminoguanidine, ischemia/reperfusion-induced increases in serum alanine aminotransferase levels and apoptosis were significantly reduced in steatotic liver compared with mice treated with phosphate buffered saline.Survival of mice with steatotic livers significantly improved by treatment with aminoguanidine.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana Chuo-ku, Chiba 260-0856, Japan.

ABSTRACT
Liver steatosis is associated with organ dysfunction after hepatic resection and transplantation which may be caused by hepatic ischemia/reperfusion injury. The aim of the current study was to determine the precise mechanism leading to hepatocyte apoptosis after steatotic liver ischemia/reperfusion. Using a murine model of partial hepatic ischemia for 90 min, we examined the levels and pathway of apoptosis, and the peroxynitrite expression, serum alanine aminotransferase levels, and liver histology 1 and 4 h after reperfusion. In the steatotic liver, the peroxynitrite expression increased after ischemia/reperfusion. Significant hepatocyte apoptosis in the steatotic liver was seen after reperfusion, caused by upregulation of cleaved caspases 9 and 3, but not caspase 8. Serum alanine aminotransferase levels were elevated and histological examination revealed severe liver injury in the steatotic liver 4 h after reperfusion. In mice treated with aminoguanidine, ischemia/reperfusion-induced increases in serum alanine aminotransferase levels and apoptosis were significantly reduced in steatotic liver compared with mice treated with phosphate buffered saline. Survival of mice with steatotic livers significantly improved by treatment with aminoguanidine. Our data suggested that the steatotic liver is vulnerable to hepatic ischemia/reperfusion, leading to significant hepatocyte apoptosis by the mitochondrial permeability transition, and thereby resulting in organ dysfunction.

No MeSH data available.


Related in: MedlinePlus