Metformin Improves Biochemical and Pathophysiological Changes in Hepatocellular Carcinoma with Pre-Existed Diabetes Mellitus Rats

Hepatocellular carcinoma (HCC) is one of the world’s most widely recognized malignant tumors that accounts for 90% of all the primary liver cancers and is a major cause of death from cancer, representing half a million deaths per year. Obesity and associated metabolic irregularities, particularly di...

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Main Authors: Maysa A. Mobasher, Mousa O. Germoush, Hala Galal El-Tantawi, Karim Samy El-Said
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Pathogens
Subjects:
Online Access:https://www.mdpi.com/2076-0817/10/1/59
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author Maysa A. Mobasher
Mousa O. Germoush
Hala Galal El-Tantawi
Karim Samy El-Said
author_facet Maysa A. Mobasher
Mousa O. Germoush
Hala Galal El-Tantawi
Karim Samy El-Said
author_sort Maysa A. Mobasher
collection DOAJ
description Hepatocellular carcinoma (HCC) is one of the world’s most widely recognized malignant tumors that accounts for 90% of all the primary liver cancers and is a major cause of death from cancer, representing half a million deaths per year. Obesity and associated metabolic irregularities, particularly diabetes mellitus (DM) and insulin resistance, are important risk factors for the advancement of HCC. Recently, retrospective studies showed that metformin (MET) could protect the hepatic tissues in pre-existing diabetes mellitus from HCC. The purpose of this study was to assess the role of MET treatment in the pre-existing diabetic rats before and after HCC induction by diethylnitrosamine (DEN). Thirty-five male Sprague Dawley albino rats were partitioned into the following groups: Group 1 (Gp1) was the control. Gp2 was injected intraperitoneally (i.p) with streptozotocin (STZ) (80 mg/kg) and DEN (50 mg/kg/7 weeks). Gp3, Gp4, and Gp5 were injected as in Gp2 and treated with MET (150 mg/kg) before and/or after HCC induction. Biochemical parameters including liver functions, lipid profile, and oxidative stress biomarkers were determined. Furthermore, histological and immunohistochemical changes were assessed in all groups. Our results illustrated that the group of rats that were treated with STZ and DEN had significant changes in both liver functions and were associated with alterations in the liver histopathological architectures. Treatment with MET before or after HCC induction ameliorated the cellular changes in the liver tissues; however, the utmost protection was found in a group of rats, which were treated with MET before and after HCC induction.
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spelling doaj.art-b34eb33d143b412db38ad4a8e84c43e72023-12-03T12:45:54ZengMDPI AGPathogens2076-08172021-01-011015910.3390/pathogens10010059Metformin Improves Biochemical and Pathophysiological Changes in Hepatocellular Carcinoma with Pre-Existed Diabetes Mellitus RatsMaysa A. Mobasher0Mousa O. Germoush1Hala Galal El-Tantawi2Karim Samy El-Said3Department of Pathology, Biochemistry Division, College of Medicine, Jouf University, Sakaka 41412, Saudi ArabiaBiology Department, College of Science, Jouf University, Sakaka 41412, Saudi ArabiaZoology Department, Faculty of Science, Ain Shams University, Cairo 11566, EgyptChemistry Department, Biochemistry Division, Faculty of Science, Tanta University, Tanta 31527, EgyptHepatocellular carcinoma (HCC) is one of the world’s most widely recognized malignant tumors that accounts for 90% of all the primary liver cancers and is a major cause of death from cancer, representing half a million deaths per year. Obesity and associated metabolic irregularities, particularly diabetes mellitus (DM) and insulin resistance, are important risk factors for the advancement of HCC. Recently, retrospective studies showed that metformin (MET) could protect the hepatic tissues in pre-existing diabetes mellitus from HCC. The purpose of this study was to assess the role of MET treatment in the pre-existing diabetic rats before and after HCC induction by diethylnitrosamine (DEN). Thirty-five male Sprague Dawley albino rats were partitioned into the following groups: Group 1 (Gp1) was the control. Gp2 was injected intraperitoneally (i.p) with streptozotocin (STZ) (80 mg/kg) and DEN (50 mg/kg/7 weeks). Gp3, Gp4, and Gp5 were injected as in Gp2 and treated with MET (150 mg/kg) before and/or after HCC induction. Biochemical parameters including liver functions, lipid profile, and oxidative stress biomarkers were determined. Furthermore, histological and immunohistochemical changes were assessed in all groups. Our results illustrated that the group of rats that were treated with STZ and DEN had significant changes in both liver functions and were associated with alterations in the liver histopathological architectures. Treatment with MET before or after HCC induction ameliorated the cellular changes in the liver tissues; however, the utmost protection was found in a group of rats, which were treated with MET before and after HCC induction.https://www.mdpi.com/2076-0817/10/1/59diabetes mellitusstreptozotocinhepatocellular carcinomadiethylnitrosaminemetformin
spellingShingle Maysa A. Mobasher
Mousa O. Germoush
Hala Galal El-Tantawi
Karim Samy El-Said
Metformin Improves Biochemical and Pathophysiological Changes in Hepatocellular Carcinoma with Pre-Existed Diabetes Mellitus Rats
Pathogens
diabetes mellitus
streptozotocin
hepatocellular carcinoma
diethylnitrosamine
metformin
title Metformin Improves Biochemical and Pathophysiological Changes in Hepatocellular Carcinoma with Pre-Existed Diabetes Mellitus Rats
title_full Metformin Improves Biochemical and Pathophysiological Changes in Hepatocellular Carcinoma with Pre-Existed Diabetes Mellitus Rats
title_fullStr Metformin Improves Biochemical and Pathophysiological Changes in Hepatocellular Carcinoma with Pre-Existed Diabetes Mellitus Rats
title_full_unstemmed Metformin Improves Biochemical and Pathophysiological Changes in Hepatocellular Carcinoma with Pre-Existed Diabetes Mellitus Rats
title_short Metformin Improves Biochemical and Pathophysiological Changes in Hepatocellular Carcinoma with Pre-Existed Diabetes Mellitus Rats
title_sort metformin improves biochemical and pathophysiological changes in hepatocellular carcinoma with pre existed diabetes mellitus rats
topic diabetes mellitus
streptozotocin
hepatocellular carcinoma
diethylnitrosamine
metformin
url https://www.mdpi.com/2076-0817/10/1/59
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AT halagalaleltantawi metforminimprovesbiochemicalandpathophysiologicalchangesinhepatocellularcarcinomawithpreexisteddiabetesmellitusrats
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