Učinci antilipidnih lijekova na kolinesterazu i parametre oksidacijskoga stresa u normolipemičnih i hiperlipemičnih štakora

doctoral thesis

• Title (english): Effects of antlipid drugs on cholinesterase and oxidative stress parameters of normolipemic and hyperlipemic rats
• Author: Antonija Vukšić
• Mentor: Jasna Lovrić (mentor)
• Committee member: Marijan Klarica (predsjednik povjerenstva)
• Committee member: Jadranka Sertić (član povjerenstva)
• Committee member: Vlasta Bradamante (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2020-12-03, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Pseudokolinesteraza (PChE), osim što ima značajnu farmakološku ulogu, zajedno s
acetilkolinesterazom sudjeluje u hidrolizi acetilkolina. Nova saznanja su da je acetilkolin
protuupalna molekula, da postoji kolinergički protuupalni put i da PChE može predstavljati
upalni biljeg kod sistemskih upala blažeg stupnja. Zato je važno poznavati lijekove koji
mijenjaju aktivnost PChE. U ovom istraživanju su ispitivani učinci simvastatina, rosuvastatina
i fenofibrata na aktivnost PChE i parametre oksidacijskog stresa kod normolipemičkih i
hiperlipemičkih štakora, budući da je u patološkim stanjima, kao što su upala i hiperlipidemija
prisutan i oksidacijski stres. Svi istraživani antilipidni lijekovi značajno su povećali aktivnost
PChE u plazmi oba soja štakora. U mozgu normolipemičnih štakora porast aktivnosti PChE
dokazan je nakon primjene statina, dok je u mozgu hiperlipemičnih štakora na porast
aktivnosti utjecao i fenofibrat. U jetrima je porast aktivnosti bio izraženiji kod hiperlipemičnih
štakora. Rezultati ispitivanja učinaka antilipidnih lijekova na parametre oksidacijskog stresa
pokazuju da simvastatin i fenofibrat u plazmi i mozgu normolipemičnih štakora pokazuju
antioksidacijski učinak, za razliku od rosuvastatina koji može djelovati prooksidacijski. U
plazmi i mozgu hiperlipemičnih štakora simvastatin ne djeluje na parametre oksidacijskog
stresa, dok fenofibrat u plazmi istog soja štakora djeluje antioksidacijski, a u mozgu
prooksidacijski. U jetrima oba soja štakora fenofibrat djeluje izrazito prooksidacijski.
Rezultati pokazuju da sva tri antilipidna lijeka utječu na aktivnost PChE i parametre
oksidacijskog stresa u normalnim i patološkim uvjetima, te stoga mogu utjecati kako na
farmakološku ulogu PChE tako i na tijek nekih patofizioloških procesa.

Abstract (english)

Beside significant pharmacological role pseudocolinesterase (PChE) is involved in hydrolysis
of acetylcholine, an anti-inflammatory molecule. Drugs can alter PChE activity. Since
oxidative stress is present in pathological conditions such as inflammation and hyperlipemia
in this study the effects of simvastatin, rosuvastatin, and fenofibrate on PChE activity and
parameters of oxidative stress in normolipemic and hyperlipemic rats were investigated. All
investigated drugs significantly increased plasma PChE activity in both strains of rats. In the
brain of normolipemic rats, increase in PChE activity was demonstrated after statin
administration, whereas in hyperlipemic rat brain, an increase in activity was also after
fenofibrate. In the liver, increase in activity was more pronounced in hyperlipemic rats.
Unlike rosuvastatin, simvastatin and fenofibrate showed antioxidant effect in plasma and
brain of normolipemic rats. In plasma of hyperlipemic rats fenofibrate showed antioxidant
effects, and in brain pro-oxidant. In the liver of both strains of rats, the effects of fenofibrate
were pro-oxidant, and effect of simvastatin was antioxidant in the liver of normolipemic and
pro-oxidant in hyperlipemic rats. Investigated drugs influenced PChE activity and oxidative
stress under normal and pathological conditions. The consequences could be change in
pharmacological role of PChE and change in course of some pathophysiological processes.

• Keywords: Životinje; Štakori; Antioksidanti; Fenofibrat; Rosuvastatin kalcij; Simvastatin; Inhibitori hidroksimetilglutaril-CoA reduktaze; Reaktivne vrste kisika; Acetilkolin; Farmaceutski pripravci; Hidroliza; Oksidativni stres; Hiperlipidemije; Jetra; Protuupalna sredstva; Upala; Mozak; Plazma
• Keywords (english): Animals; Rats; Antioxidants; Fenofibrate; Rosuvastatin Calcium; Simvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Reactive Oxygen Species; Acetylcholine; Pharmaceutical Preparations; Hydrolysis; Oxidative Stress; Hyperlipidemias; Liver; Anti-Inflammatory Agents; Inflammation; Brain; Plasma
• Language: croatian
• URN:NBN: urn:nbn:hr:105:491413
• Project: Number: 108-0000000-0013; Title: Serumske esteraze, leptin, lipidi i antilipidni lijekovi; Title: Serum esterases, leptin, lipids and antilipid drugs; Leader: Vlasta Bradamante; Jurisdiction: Croatia; Funder: MZOS; Funding stream: ZP
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 139 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-03-19 09:54:49