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Mediators of hypoxia in a rat model of sterile-induced acute liver injury.

ABSTRACT: BACKGROUND:The liver plays a key role in iron homeostasis during injury and hypoxia. METHODS:For induction of liver injury, thioacetamide (TAA) was administered intraperitoneally to male Sprague Dawley rats. Animals were sacrificed at 0, 1, 3, 6, 12, 24, 48, 72 and 96 h. Serum, liver, spleen and heart tissues were collected from control and TAA-treated rats. Tissue sections were prepared for immunohistochemical studies. Nuclear and cytoplasmic proteins were isolated for Western blot analysis. RESULTS:Hypoxia inducible factor (HIF)-1? and ED1 positive cells accumulated around the portal field and the interlobular space within 12 hours after TAA administration. Accordingly, Western blot analysis of liver tissue showed an early increase of HIF1? followed by a decrease at 48 h to 96 h. For Erythropoietin (EPO), as well as for HIF1- and -2?, a time-dependent translocation was observed from the cytoplasmic to the nuclear compartment. CONCLUSION:Our data suggest that the TAA-induced acute liver damage generates HIF-1? dependent rescue mechanisms with translocation of EPO from the cytoplasmic to the nuclear compartment. Enhanced iron transport into the liver could be necessary for increased metabolic activities during repair processes.

SUBMITTER: Ahmad S

PROVIDER: S-EPMC6966030 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Mediators of hypoxia in a rat model of sterile-induced acute liver injury.

Ahmad Shakil S Cameron Silke S Naz Naila N Moriconi Federico F

International journal of clinical and experimental pathology 20171201 12

<h4>Background</h4>The liver plays a key role in iron homeostasis during injury and hypoxia.<h4>Methods</h4>For induction of liver injury, thioacetamide (TAA) was administered intraperitoneally to male Sprague Dawley rats. Animals were sacrificed at 0, 1, 3, 6, 12, 24, 48, 72 and 96 h. Serum, liver, spleen and heart tissues were collected from control and TAA-treated rats. Tissue sections were prepared for immunohistochemical studies. Nuclear and cytoplasmic proteins were isolated for Western bl ...[more]

PMID: 31966502

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Mediators of hypoxia in a rat model of sterile-induced acute liver injury.

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Mediators of hypoxia in a rat model of sterile-induced acute liver injury.

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