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The objective of study was to investigate the effects of different doses of simvastatin and fenofibrate on malondialdehyde (MDA) and reduced glutathione (GSH) in the plasma, liver, and brain tissue of male normolipidaemic and hyperlipidaemic rats. Normolipidaemic (Wistar) rats were receiving 10 or 50 mg/kg a day of simvastatin or 30 or 50 mg/kg a day of fenofibrate. Hyperlipidaemic (Zucker) rats were receiving 50 mg/kg/day of simvastatin or 30 mg/kg/day of fenofibrate. Control normolipidaemic and hyperlipidaemic rats were receiving saline. Simvastatin, fenofibrate, and saline were administered by gavage for three weeks. In normolipidaemic rats simvastatin and fenofibrate showed similar and dose-independent effects on plasma and brain MDA and GSH concentrations. Generally, plasma and brain MDA decreased, while brain GSH concentration increased. In hyperlipidaemic rats simvastatin did not affect plasma and brain MDA and GSH concentrations but significantly decreased liver GSH. Fenofibrate decreased plasma and liver MDA but increased brain MDA. In both rat strains fenofibrate significantly decreased liver GSH concentrations, most likely because fenofibrate metabolites bind to GSH. Our findings suggest that simvastatin acts as an antioxidant only in normolipidaemic rats, whereas fenofibrate acts as an antioxidant in both rat strains., Cilj ovog istraživanja bio je istražiti učinke različitih doza simvastatina i fenofibrata na malondialdehid (MDA) i reducirani glutation (GSH) u plazmi, jetri i mozgu mužjaka normolipidemičnih (Wistar) i hiperlipidemičnih (Zucker) štakora. Na prvim dvjema eksperimentalnim skupinama normolipidemičnih štakora simvastatin je primijenjen u dozama 10 ili 50 mg/kg dnevno, a fenofibrat na trećoj i četvrtoj skupini u dozama od 30 i 50 mg/kg/dan. Prva eksperimentalna skupina hiperlipidemičnih štakora primala je simvastatin 50 mg/kg/dan, a druga fenofibrat 30 mg/kg/dan. Kontrolne skupine normolipidemičnih i hiperlipidemičnih štakora primale su fiziološku otopinu. Simvastatin, fenofibrat i fiziološka otopina primjenjivani su oralno tijekom tri tjedna. U plazmi i mozgu normolipidemičnih štakora simvastatin I fenofibrat pokazali su slične i o dozi neovisne učinke na koncentracije MDA i GSH. Općenito, MDA je bio smanjen, a koncentracija GSH bila je povećana. U hiperlipidemičnih štakora simvastatin nije utjecao na koncentraciju MDA i GSH, ali je prouzročio značajno smanjenje GSH u jetri. Fenofibrat je smanjio MDA u plazmi i jetri te povećao MDA u mozgu. U oba soja štakora fenofibrat je značajno smanjio koncentraciju GSH u jetri, vjerojatno zbog konjugacije GSH s nekim metabolitima fenofibrata. Prema našim rezultatima, simvastatin djeluje antioksidacijski samo u normolipidemičnih štakora, a antioksidacijski učinak fenofibrata prisutan je u oba soja.

The study objective was to test the hypothesis that simvastatin and fenofibrate should cause an increase in butyrylcholinesterase (BuChE) activity not only in the plasma and liver but also in the brain of normolipidemic and hyperlipidemic rats. Catalytic enzyme activity was measured using acetylthiocholine (ATCh) and butyrylthiocholine (BTCh) as substrates. Normolipidemic and hyperlipidemic rats were divided in four groups receiving 50 mg/kg of simvastatin a day or 30 mg/kg of fenofibrate a day for three weeks and three control groups receiving saline. Simvastatin and fenofibrate caused an increase in brain BuChE activity in both normo- and hyperlipidemic rats regardless of the substrate. The increase with BTCh as substrate was significant and practically the same in normolipidemic and hyperlipidemic rats after simvastatin treatment (14–17% vs controls). Simvastatin and fenofibrate also increased liver and plasma BuChE activity in both normolipidemic and hyperlipidemic rats regardless of the substrate. In most cases the increase was significant. Considering the important role of BuChE in cholinergic transmission as well as its pharmacological function, it is necessary to continue investigations of the effects of lipid-lowering drugs on BuChE activity., Cilj ispitivanja bio je u normolipidemičnih i hiperlipidemičnih štakora potvrditi pretpostavku da simvastatin (SIMV) I fenofibrat (FENO) ne uzrokuju samo povećanje aktivnosti butirilkolinesteraze (BuChE) u plazmi i jetri nego i povećavaju aktivnosti BuChE u mozgu. Katalitička aktivnost enzima mjerena je upotrebom acetiltiokolina (ATCh) i butiriltiokolina (BTCh) kao supstrata. Normolipidemični i hiperlipidemični štakori raspoređeni su u eksperimentalne skupine, koje su tri tjedna primale SIMV 50 mg/kg na dan ili FENO 30 mg/kg na dan, dok su kontrolne skupine primale fiziološku otopinu. I SIMV i FENO uglavnom su izazvali povećanje aktivnosti BuChE u mozgu obaju sojeva štakora bez obzira na korišteni supstrat. Aktivnosti BuChE mjerene BTCh kao supstratom bile su značajno veće u odnosu na kontrolne vrijednosti u mozgu normolipidemičih štakora nakon primjene SIMV te u mozgu hiperlipidemičnih štakora nakon primjene obaju agensa (14‒17%, p