Utjecaj antilipidnih lijekova na esteraze, lipide i leptin u biološkom materijalu štakora [The influence of antilipid drugs on esterases, lipids and leptin in rats]

Macan, Marija (2012) Utjecaj antilipidnih lijekova na esteraze, lipide i leptin u biološkom materijalu štakora [The influence of antilipid drugs on esterases, lipids and leptin in rats]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

It is believed that paraoxonase 1 (PON1) and butyrylcholinesterase (BuChE) are important in the lipid metabolism. PON1 is supposed to be able to prevent the oxidation of plasma lipoproteins. BuChE might be included in the metabolism of choline and LDL. It seems that leptin is also involved in the lipid metabolism. Beside well-known lipid effects expressed by antilipid drugs, some studies indicate their other important non-lipid (pleiotropic) effects. Therefore the aims of this study were to investigate the influence of multiple applications of atorvastatin, pravastatin, simvastatin and gemfibrozil on esterases, lipids, malondyaldehide and leptin. All studies were performed on normolipidemic Wistar rats. Atorvastatin and pravastatin increased, and simvastatin decreased PON1 activity in serum and liver. All changes on plasma lipids were typical for the used drugs and treated animals. All of the statins decreased the malondyaldehide concentration (antioxidative effect), simvastatin in particular. The opposite effects were found in animals treated by gemfibrozil, i.e. the decrease of PON1 activity in liver and increase of malondyaldehide concentration (oxidative effect). Statins caused the increase of BuChE activity in plasma and liver, while gemfibrozil raised its activity in plasma. The low concentration of plasma leptin was measured after the administration of gemfibrozil and also of low doses of statins. According to these results, when compared with gemfibrozil, statins show preferable pleiotropic, especially antioxidative effects.

Abstract in Croatian

Smatra se da esteraze paraoksonaza 1 (PON1), putem sprečavanja oksidacije lipoproteina plazme i butirilkolinesteraza (BuChE), svojim sudjelovanjem u metabolizmu kolina i lipoproteina male gustoće, utječu na metabolizam lipida. Pretpostavlja se da i leptin također sudjeluje u metabolizmu lipida. Osim dobro poznatih učinaka antilipidnih lijekova na lipide, sve važniji postaju njihovi ne-lipidni (pleiotropni) učinci. Stoga su ciljevi ovog rada bili ispitati i usporediti djelovanje višekratne primjene atorvastatina, pravastatina, simvastatina i gemfibrozila na esteraze, lipide, malondialdehid i leptin. Sva istraživanja su provedena na normolipidemičkim Wistar štakorima. Atorvastatin i pravastatin su izazvali porast, a simvastatin pad katalitičke aktivnosti serumske i jetrene PON1. Promjene u koncentracijama lipida plazme bile su karakteristične kako za same primjenjene lijekove tako i za korištenu životinjsku vrstu. Svi statini su smanjili koncentraciju malondialdehida (antioksidacijski učinak), osobito simvastatin. Suprotno je bilo u životinja tretiranih gemfibrozilom, tj. rezultati su jasno pokazali da isti lijek smanjuje aktivnost PON1 u jetri i povećava koncentraciju malondialdehida (oksidacijski učinak). Statini su povećali aktivnost BuChE u plazmi i jetri, a gemfibrozil u plazmi. Smanjenje plazmatske koncentracije leptina je izmjereno nakon primjene gemfibrozila i manjih doza statina. Prema ovim rezultatima, statini pokazuju bolje pleiotropne učinke od gemfibrozila, naročito kada je u pitanju njihov antioksidacijski učinak.

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