Abstract
Abstract in English, Croatian 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. Valproat je najčešće korišten antiepileptik, čiji štetni učinci uključuju masnu jetru (steatozu) i dislipidemiju. Cilj istraživanja bio je utvrditi kako će prirodni flavonoid i antioksidans naringin u interakciji s valproatom ublažiti navedene štetne učinke. Mužjaci miševa C57BL6 bili su svakodnevno tijekom 10 dana izloženi valproatu u dozi od 150 mg/kg i naringinu u dozi od 25 mg/kg te njihovim međusobnim kombinacijama u istim dozama. Nakon pokusnog razdoblja usporedili smo razinu serumskih triglicerida, kolesterola, LDL, HDL i VLDL, jetrene markere PPAR-alfa, PGC-1 alfa, ACOX1 i Nrf2 te antioksidacijske markere SOD, CAT i GSH u jetri. Svaka je jetra analizirana histološki. Valproat je povećao parametre peroksidacije lipida i izazvao izraženu mikrovezikularnu steatozu u cijelom jetrenom lobulu u svim acinarnim zonama, ali je istodobna primjena naringina ograničila steatozu na periferiju lobula. Osim toga, naringin je uspostavio normalnu ravnotežu serumskoga kolesterola, LDL i triglicerida te jetrenih markera PPAR-alfa i PGC-1 alfa, ACOX1 i MDA. Također je povećao aktivnost SOD-a. Svi ovi nalazi upućuju na to da naringin modulira ključne regulatore metabolizma lipida i da ga treba dalje istražiti u ovome modelu, bilo samog ili u kombinaciji s drugim lijekovima ili molekulama za regulaciju lipida.