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Effects of Naringin and Valproate Interaction on Liver Steatosis and Dyslipidaemia Parameters in Male C57BL6 Mice

Valproate is a common antiepileptic drug whose adverse effects include liver steatosis and dyslipidaemia. The aim of our study was to see how natural flavonoid antioxidant naringin would interact with valproate and attenuate these adverse effects. For this reason we treated male C57BL6 mice with a c...

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Autores principales: Jutrić, David, Đikić, Domagoj, Boroš, Almoš, Odeh, Dyna, Drozdek, Sandra Domjanić, Gračan, Romana, Dragičević, Petar, Crnić, Irena, Jurčević, Irena Landeka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Sciendo 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8999592/
https://www.ncbi.nlm.nih.gov/pubmed/35390239
http://dx.doi.org/10.2478/aiht-2022-73-3608
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author Jutrić, David
Đikić, Domagoj
Boroš, Almoš
Odeh, Dyna
Drozdek, Sandra Domjanić
Gračan, Romana
Dragičević, Petar
Crnić, Irena
Jurčević, Irena Landeka
author_facet Jutrić, David
Đikić, Domagoj
Boroš, Almoš
Odeh, Dyna
Drozdek, Sandra Domjanić
Gračan, Romana
Dragičević, Petar
Crnić, Irena
Jurčević, Irena Landeka
author_sort Jutrić, David
collection PubMed
description Valproate is a common antiepileptic drug whose adverse effects include liver steatosis and dyslipidaemia. The aim of our study was to see how natural flavonoid antioxidant naringin would interact with valproate and attenuate these adverse effects. For this reason we treated male C57BL6 mice with a combination of 150 mg/kg of valproate and 25 mg/kg naringin every day for 10 days and compared their serum triglycerides, cholesterol, LDL, HDL, VLDL, and liver PPAR-alpha, PGC-1 alpha, ACOX1, Nrf2, SOD, CAT, GSH, and histological signs of steatosis. Valproate increased lipid peroxidation parameters and caused pronounced microvesicular steatosis throughout the hepatic lobule in all acinar zones, but naringin co-administration limited steatosis to the lobule periphery. In addition, it nearly restored total serum cholesterol, LDL, and triglycerides and liver ACOX1 and MDA to control levels. and upregulated PPAR-alpha and PGC-1 alpha, otherwise severely downregulated by valproate. It also increased SOD activity. All these findings suggest that naringin modulates key lipid metabolism regulators and should further be investigated in this model, either alone or combined with other lipid regulating drugs or molecules.
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spelling pubmed-89995922022-06-13 Effects of Naringin and Valproate Interaction on Liver Steatosis and Dyslipidaemia Parameters in Male C57BL6 Mice Jutrić, David Đikić, Domagoj Boroš, Almoš Odeh, Dyna Drozdek, Sandra Domjanić Gračan, Romana Dragičević, Petar Crnić, Irena Jurčević, Irena Landeka Arh Hig Rada Toksikol Original Article Valproate is a common antiepileptic drug whose adverse effects include liver steatosis and dyslipidaemia. The aim of our study was to see how natural flavonoid antioxidant naringin would interact with valproate and attenuate these adverse effects. For this reason we treated male C57BL6 mice with a combination of 150 mg/kg of valproate and 25 mg/kg naringin every day for 10 days and compared their serum triglycerides, cholesterol, LDL, HDL, VLDL, and liver PPAR-alpha, PGC-1 alpha, ACOX1, Nrf2, SOD, CAT, GSH, and histological signs of steatosis. Valproate increased lipid peroxidation parameters and caused pronounced microvesicular steatosis throughout the hepatic lobule in all acinar zones, but naringin co-administration limited steatosis to the lobule periphery. In addition, it nearly restored total serum cholesterol, LDL, and triglycerides and liver ACOX1 and MDA to control levels. and upregulated PPAR-alpha and PGC-1 alpha, otherwise severely downregulated by valproate. It also increased SOD activity. All these findings suggest that naringin modulates key lipid metabolism regulators and should further be investigated in this model, either alone or combined with other lipid regulating drugs or molecules. Sciendo 2022-04-07 /pmc/articles/PMC8999592/ /pubmed/35390239 http://dx.doi.org/10.2478/aiht-2022-73-3608 Text en © 2022 David Jutrić, Domagoj Đikić, Almoš Boroš, Dyna Odeh, Sandra Domjanić Drozdek, Romana Gračan, Petar Dragičević, Irena Crnić, Irena Landeka Jurčević, published by Sciendo https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Original Article
Jutrić, David
Đikić, Domagoj
Boroš, Almoš
Odeh, Dyna
Drozdek, Sandra Domjanić
Gračan, Romana
Dragičević, Petar
Crnić, Irena
Jurčević, Irena Landeka
Effects of Naringin and Valproate Interaction on Liver Steatosis and Dyslipidaemia Parameters in Male C57BL6 Mice
title Effects of Naringin and Valproate Interaction on Liver Steatosis and Dyslipidaemia Parameters in Male C57BL6 Mice
title_full Effects of Naringin and Valproate Interaction on Liver Steatosis and Dyslipidaemia Parameters in Male C57BL6 Mice
title_fullStr Effects of Naringin and Valproate Interaction on Liver Steatosis and Dyslipidaemia Parameters in Male C57BL6 Mice
title_full_unstemmed Effects of Naringin and Valproate Interaction on Liver Steatosis and Dyslipidaemia Parameters in Male C57BL6 Mice
title_short Effects of Naringin and Valproate Interaction on Liver Steatosis and Dyslipidaemia Parameters in Male C57BL6 Mice
title_sort effects of naringin and valproate interaction on liver steatosis and dyslipidaemia parameters in male c57bl6 mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8999592/
https://www.ncbi.nlm.nih.gov/pubmed/35390239
http://dx.doi.org/10.2478/aiht-2022-73-3608
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