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.
Keywords: Wistar rats; Wistar štakori; Zucker rats; Zucker štakori; lijekovi za snižavanje lipida; lipid peroxidation; lipid-lowering drugs; oksidacijski stres; oxidative stress; peroksidacija lipida.
© 2023 Antonija Vukšić et al., published by Sciendo.