Effects of naringin and valproate interaction on liver steatosis and dyslipidaemia parameters in male C57BL/6 mice

  • David Jutrić University of Zagreb Faculty of Science, Zagreb, Croatia
  • Domagoj Đikić Department of Animal Physiology, Faculty of Science, University of Zagreb
  • Almoš Boroš University of Zagreb Faculty of Science, Zagreb, Croatia
  • Dyna Odeh University of Zagreb Faculty of Science, Zagreb, Croatia
  • Sandra Domjanić Drozdek University of Applied Health Sciences, Zagreb, Croatia
  • Romana Gračan University of Zagreb Faculty of Science, Zagreb, Croatia
  • Petar Dragičević University of Zagreb School of Medicine, Zagreb Croatia
  • Irena Crnić University of Zagreb Faculty of Food Technology and Biotechnology, Zagreb, Croatia
  • Irena Landeka Jurčević University of Zagreb Faculty of Food Technology and Biotechnology, Zagreb, Croatia
Keywords: ACOX1, cholesterol, dyslipidaemia, lipid regulating transcription factors, Nrf2, oxidative stress, PPAR alpha, PGC-1 alpha

Abstract

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 C57BL/6 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.

Author Biography

Domagoj Đikić, Department of Animal Physiology, Faculty of Science, University of Zagreb

Associated professor

Department of Animal Physiology

Faculty of Science

University of Zagreb

Published
2022-03-23
How to Cite
1.
Jutrić D, Đikić D, Boroš A, Odeh D, Domjanić Drozdek S, Gračan R, Dragičević P, Crnić I, Landeka Jurčević I. Effects of naringin and valproate interaction on liver steatosis and dyslipidaemia parameters in male C57BL/6 mice. Arh Hig Rada Toksikol [Internet]. 2022Mar.23 [cited 2022Aug.14];73(1). Available from: https://arhiv.imi.hr/index.php/arhiv/article/view/1454
Section
Original article