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Vol 55, No 3 (2017)
Original paper
Submitted: 2017-02-27
Accepted: 2017-09-11
Published online: 2017-09-19
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Repression of the Notch pathway prevents liver damage in streptozotocin-induced diabetic mice

Eda Acikgoz, Huseyin Aktug, Gurkan Yigitturk, Kenan Demir, Ummu Guven, Fahriye Duzagac, Fatih Oltulu1, Altug Yavasoglu, Gulperi Oktem
DOI: 10.5603/FHC.a2017.0014
·
Pubmed: 28994095
·
Folia Histochem Cytobiol 2017;55(3):140-148.
Affiliations
  1. Ege University, Faculty of Medicine, Department of Histology and Embryology, Izmir, Turkey

open access

Vol 55, No 3 (2017)
ORIGINAL PAPERS
Submitted: 2017-02-27
Accepted: 2017-09-11
Published online: 2017-09-19

Abstract

Introduction. Sunitinib is an oral inhibitor of vascular endothelial growth factor that is used to treat a variety of cancer. There are limited data regarding the effect of sunitinib on diabetes. In the liver, Notch signaling plays an important role in liver tissue development and homeostasis and its dysfunction is associated with liver pathol­ogies. The aim of the present study is to investigate the effects of sunitinib on streptozotocin (STZ)-induced diabetic liver in mice models.

Material and methods. An experimental diabetes mellitus (DM) model was created in 28 male CD-1 mice. Twenty-eight male CD-1 mice divided in four groups (n = 7 each) were used; control mice (C), control mice treated with sunitinib (C + S), diabetic mice (DM), and diabetic mice treated with sunitinib (DM + S) for four weeks. The histopathological changes in the liver were examined by histochemistry and immunohistochemistry. Immunoreactivity of Notch1, Jagged1, DLL-1 and VEGF were evaluated in control and diabetic mice after sunitinib treatment.

Results. The significant morphological changes in the liver were mostly seen in hepatocytes that were hyper­trophied in the DM mice, with an increased amount of eosinophilic granules; moreover, some hepatocytes contained empty vacuole-like structures. The livers of the DM mice revealed increased deposition of collagen fibers. After sunitinib treatment the hepatocytes and hepatic lobules had almost similar morphology to control mice. The immunoreactivities of Notch1, Jagged1, DLL-1 and VEGF in hepatocytes were significantly lower in the DM group when compared with the C, DM + S and C + S group treated with sunitinib.

Conclusions. These results suggest that sunitinib effectively protects the liver from diabetes-induced damage through the inhibition of the Notch pathway.

Abstract

Introduction. Sunitinib is an oral inhibitor of vascular endothelial growth factor that is used to treat a variety of cancer. There are limited data regarding the effect of sunitinib on diabetes. In the liver, Notch signaling plays an important role in liver tissue development and homeostasis and its dysfunction is associated with liver pathol­ogies. The aim of the present study is to investigate the effects of sunitinib on streptozotocin (STZ)-induced diabetic liver in mice models.

Material and methods. An experimental diabetes mellitus (DM) model was created in 28 male CD-1 mice. Twenty-eight male CD-1 mice divided in four groups (n = 7 each) were used; control mice (C), control mice treated with sunitinib (C + S), diabetic mice (DM), and diabetic mice treated with sunitinib (DM + S) for four weeks. The histopathological changes in the liver were examined by histochemistry and immunohistochemistry. Immunoreactivity of Notch1, Jagged1, DLL-1 and VEGF were evaluated in control and diabetic mice after sunitinib treatment.

Results. The significant morphological changes in the liver were mostly seen in hepatocytes that were hyper­trophied in the DM mice, with an increased amount of eosinophilic granules; moreover, some hepatocytes contained empty vacuole-like structures. The livers of the DM mice revealed increased deposition of collagen fibers. After sunitinib treatment the hepatocytes and hepatic lobules had almost similar morphology to control mice. The immunoreactivities of Notch1, Jagged1, DLL-1 and VEGF in hepatocytes were significantly lower in the DM group when compared with the C, DM + S and C + S group treated with sunitinib.

Conclusions. These results suggest that sunitinib effectively protects the liver from diabetes-induced damage through the inhibition of the Notch pathway.

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Keywords

diabetes; streptozotocin; mouse; liver; sunitinib; Notch1; Jagged1; DLL-1; VEGF; IHC

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About this article
Title

Repression of the Notch pathway prevents liver damage in streptozotocin-induced diabetic mice

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 55, No 3 (2017)

Article type

Original paper

Pages

140-148

Published online

2017-09-19

Page views

1977

Article views/downloads

1765

DOI

10.5603/FHC.a2017.0014

Pubmed

28994095

Bibliographic record

Folia Histochem Cytobiol 2017;55(3):140-148.

Keywords

diabetes
streptozotocin
mouse
liver
sunitinib
Notch1
Jagged1
DLL-1
VEGF
IHC

Authors

Eda Acikgoz
Huseyin Aktug
Gurkan Yigitturk
Kenan Demir
Ummu Guven
Fahriye Duzagac
Fatih Oltulu
Altug Yavasoglu
Gulperi Oktem

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