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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| Format: | Article |
| Language: | English |
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Sciendo
2022-04-01
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| Series: | Arhiv za Higijenu Rada i Toksikologiju |
| Subjects: | |
| Online Access: | https://doi.org/10.2478/aiht-2022-73-3608 |
| _version_ | 1811289353939320832 |
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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 | DOAJ |
| 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. |
| first_indexed | 2024-04-13T03:53:23Z |
| format | Article |
| id | doaj.art-98b75cb64fab4e52ba0c7622aecbc1e7 |
| institution | Directory Open Access Journal |
| issn | 1848-6312 |
| language | English |
| last_indexed | 2024-04-13T03:53:23Z |
| publishDate | 2022-04-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Arhiv za Higijenu Rada i Toksikologiju |
| spelling | doaj.art-98b75cb64fab4e52ba0c7622aecbc1e72022-12-22T03:03:43ZengSciendoArhiv za Higijenu Rada i Toksikologiju1848-63122022-04-01731718210.2478/aiht-2022-73-3608Effects of naringin and valproate interaction on liver steatosis and dyslipidaemia parameters in male C57BL6 miceJutrić David0Đikić Domagoj1Boroš Almoš2Odeh Dyna3Drozdek Sandra Domjanić4Gračan Romana5Dragičević Petar6Crnić Irena7Jurčević Irena Landeka8University of Zagreb Faculty of Science, Zagreb, CroatiaUniversity of Zagreb Faculty of Science, Zagreb, CroatiaUniversity of Zagreb Faculty of Science, Zagreb, CroatiaUniversity of Zagreb Faculty of Science, Zagreb, CroatiaUniversity of Applied Health Sciences, Zagreb, CroatiaUniversity of Zagreb Faculty of Science, Zagreb, CroatiaUniversity of Zagreb School of Medicine, ZagrebCroatiaUniversity of Zagreb Faculty of Food Technology and Biotechnology, Zagreb, CroatiaUniversity of Zagreb Faculty of Food Technology and Biotechnology, Zagreb, CroatiaValproate 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.https://doi.org/10.2478/aiht-2022-73-3608acox1cholesteroldyslipidaemialipid regulating transcription factorsnrf2oxidative stressppar-alphapgc-1 alphaacox1kolesteroldislipidemijanrf2ppar-alfapgc-1 alfaoksidacijski strestranskripcijski faktori za regulaciju lipida |
| spellingShingle | 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 Arhiv za Higijenu Rada i Toksikologiju acox1 cholesterol dyslipidaemia lipid regulating transcription factors nrf2 oxidative stress ppar-alpha pgc-1 alpha acox1 kolesterol dislipidemija nrf2 ppar-alfa pgc-1 alfa oksidacijski stres transkripcijski faktori za regulaciju lipida |
| 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 | acox1 cholesterol dyslipidaemia lipid regulating transcription factors nrf2 oxidative stress ppar-alpha pgc-1 alpha acox1 kolesterol dislipidemija nrf2 ppar-alfa pgc-1 alfa oksidacijski stres transkripcijski faktori za regulaciju lipida |
| url | https://doi.org/10.2478/aiht-2022-73-3608 |
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