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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.


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(A) Hepatocellular injury as indicated by serum levels of alanine aminotransferase (ALT). Samples were obtained from mice undergoing the sham operation or ischemia for 90 min and reperfusion (I/R). Values represent the mean ± SEM with n = 6 per group. *p<0.05, compared to the WT group. Histological findings of the liver assessed by hematoxylin and eosin staining. (B) Sham operated WT group. (C) Sham operated FL group. (D) WT group 4 h after reperfusion. (E) FL group 4 h after reperfusion. Original magnification ×100.
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Figure 4: (A) Hepatocellular injury as indicated by serum levels of alanine aminotransferase (ALT). Samples were obtained from mice undergoing the sham operation or ischemia for 90 min and reperfusion (I/R). Values represent the mean ± SEM with n = 6 per group. *p<0.05, compared to the WT group. Histological findings of the liver assessed by hematoxylin and eosin staining. (B) Sham operated WT group. (C) Sham operated FL group. (D) WT group 4 h after reperfusion. (E) FL group 4 h after reperfusion. Original magnification ×100.

Mentions: To assess the extent of hepatic injury during ischemia/reperfusion, serum levels of ALT were examined (n = 6, respectively). The serum ALT levels in the FL mice were significantly increased relative to the WT mice 1 and 4 h after reperfusion (Fig. 4A). The histological findings showed that focal hepatic necrosis was observed in the FL mice 4 h after reperfusion (Fig. 4B–E).


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)

(A) Hepatocellular injury as indicated by serum levels of alanine aminotransferase (ALT). Samples were obtained from mice undergoing the sham operation or ischemia for 90 min and reperfusion (I/R). Values represent the mean ± SEM with n = 6 per group. *p<0.05, compared to the WT group. Histological findings of the liver assessed by hematoxylin and eosin staining. (B) Sham operated WT group. (C) Sham operated FL group. (D) WT group 4 h after reperfusion. (E) FL group 4 h after reperfusion. Original magnification ×100.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 4: (A) Hepatocellular injury as indicated by serum levels of alanine aminotransferase (ALT). Samples were obtained from mice undergoing the sham operation or ischemia for 90 min and reperfusion (I/R). Values represent the mean ± SEM with n = 6 per group. *p<0.05, compared to the WT group. Histological findings of the liver assessed by hematoxylin and eosin staining. (B) Sham operated WT group. (C) Sham operated FL group. (D) WT group 4 h after reperfusion. (E) FL group 4 h after reperfusion. Original magnification ×100.
Mentions: To assess the extent of hepatic injury during ischemia/reperfusion, serum levels of ALT were examined (n = 6, respectively). The serum ALT levels in the FL mice were significantly increased relative to the WT mice 1 and 4 h after reperfusion (Fig. 4A). The histological findings showed that focal hepatic necrosis was observed in the FL mice 4 h after reperfusion (Fig. 4B–E).

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