Metaboličke i fiziološke promjene u jetri miša C57BL6 nakon združenog unosa lijeka valproata i polifenola naringenina

master's thesis

• Title (english): Liver metabolic and physiological changes after synergistic intake of the medicament valproate and polyphenol naringenin in C57BL6 mouse
• Author: Almos Boroš
• Mentor: Domagoj Đikić (mentor)
• Committee member: Domagoj Đikić (predsjednik povjerenstva)
• Committee member: Petar Kružić (član povjerenstva)
• Committee member: Tomislav Ivanković (član povjerenstva)
• Committee member: Željka Vidaković-Cifrek (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2020-07-16, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Valproat je razgranata kratkolančana masna kiselina korištena kao antiepileptički lijek čija primjena uzrokuje nakupljanje lipida u jetri i promjene u metabolizmu lipida i ugljikohidrata. Naringenin je spoj iz biljaka porodice citrusa poznat po svojim hepatoprotektivnim, antioksidativnim i antihiperglikemijskim svojstvima. Cilj ovoga rada bio je utvrditi hoće li u muških C57 miševa koadministracija polifenola naringenina sa valproatom umanjiti štetne učinke valproata na jetru. Nakon 15 dana tretmana miševa izmjereni su serumski parametri lipidnog indeksa, aktivnosti alanin aminotransferaze (ALT), ukupnih proteina, albumina, globulina,i glukoze. U tkivu jetre izmjereni su pokazatelji lipidne peroksidacije (malondialdehid/MDA) i aktivnosti antioksidativnih enzima superoksid dismutaze (SOD) i katalaze (CAT). Na tkivnim prerezima jetre bojani su lipidi Oil Red O metodom i metodom steroidnih dehidrogenaza vizualizirane aktivnosti steroidnih dehidrogenaza. Naringenin u kotretmanu sa valproatom u ovom istraživanju pokazao je manje znakova oštećenja hepatocita temeljem ALT aktivnosti, ali i najviši lipidni indeks, te nakupljanje lipida u jetri (steatozu). Na markere lipidne peroksidacije (MDA) i antioksidacijske enzime (SOD i CAT) koadministracija naringenina u životinja nije proizvela uniformni očekivani zaštitini učinak, već su aktivnosti bile neznačajno različite od valproatnog i kontrolnog tretmana. Narigenin samostalno i u kotretmanu sa valproatom producirao je izraženu hiperglikemiju veću u odnosu na samostalni tretman valproatom.

Abstract (english)

Valproate is a branched short chain fatty acid used as an antiepileptic drug. It's usage induces accumulation of lipids in hepatic tissue and changes in lipid and carbohydrate metabolism. Naringen is a substance produced mostly by plants of the citrus familiy known for its hepatoprotective, antioxidative and antihyperglychaemic effects. The aim of this study was to determine if coadministration of a polyphenol naringenin with valproate will alleviate the hepatotoxic effects of valproate in male C57 mice. After 15 days of treatment, serum parameters of lipid index, alanine aminotransferase (ALT) activity, total protein, albumin, globulin, and glucose content were measured. In hepatic tissue measurements were made of lipid peroxidation markers (malondialdehyde/MDA) and antioxidative enzyme activity, more precisely superoxide dismutase (SOD) and catalase (CAT). Hepatic tissue slices were stained for lipids via Oil Red O method and steroid dehydrogenase activity was visualised via Steroid dehydrogenase method. In this study naringenin, co administered with valproate, produced less hepatocyte damage as indicated by ALT activity, yet produced the highest serum lipid index and caused elevated accumulation of lipids in liver (hepatic steatosis). On lipid peroxidation marker (MDA) and antioxidative enzymes (SOD and CAT) naringenin coadministration with valproate produced no uniform protective effect and their parameters were insignificantly different in comparison to the valproate treated and control groups. Naringenin alone and co administered with valproate produced pronounced hyperglychaemia larger than that of valproate treatment alone.

• Keywords: valproat; naringenin; oksidativni stres; serumski markeri; glukoza; lipidna peroksidacija; superoksid dismutaza; katalaza; Oil Red O
• Keywords (english): valproate; naringenin; oxidative stress; serum markers; glucose; lipid peroxidation; superoxide dismutase; catalase; Oil Red O
• Language: croatian
• URN:NBN: urn:nbn:hr:217:980067
• Study programme: Title: Experimental Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra eksperimentalne biologije (sveučilišni/a magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-11-29 12:03:42