Original scientific paper
https://doi.org/10.2478/aiht-2023-74-3697
The effects of simvastatin and fenofibrate on malondialdehyde and reduced glutathione concentrations in the plasma, liver, and brain of normolipidaemic and hyperlipidaemic rats
Antonija Vukšić
; Clinical Hospital Centre Zagreb, Department of Neurology, Zagreb, Croatia
Dubravka Rašić
; Institute for Medical Research and Occupational Health, Unit of Toxicology, Zagreb, Croatia
Suzana Žunec
; Institute for Medical Research and Occupational Health, Unit of Toxicology, Zagreb, Croatia
Tamara Božina
; University of Zagreb School of Medicine, Department of Medical Chemistry, Biochemistry, and Clinical Chemistry, Zagreb, Croatia
Paško Konjevoda
; Ruđer Bošković Institute, NMR Centre, Zagreb, Croatia
Jasna Lovrić
; University of Zagreb School of Medicine, Department of Medical Chemistry, Biochemistry, and Clinical Chemistry, Zagreb, Croatia
Marinko Bilušić
; Polyclinic Bonifarm, Department of Clinical Pharmacology and Toxicology, Zagreb, Croatia
Vlasta Bradamante
; University of Zagreb School of Medicine, Department of Pharmacology, Zagreb, Croatia
Abstract
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.
Keywords
lipid peroxidation; lipid-lowering drugs; oxidative stress; Wistar rats; Zucker rats
Hrčak ID:
296530
URI
Publication date:
28.3.2023.
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