title: Effects of simvastatin on malondialdehyde level and esterase activity in plasma and tissue of normolipidemic rats.
abstract: BACKGROUND
  We investigated the possible non-lipid effects of simvastatin (SIMV) on paraoxonase 1 (PON1) and butyrylcholinesterase (BuChE) activity, as well as on malondialdehyde (MDA) levels in normolipidemic rats.
  
  
  METHODS
  Two experimental groups of Wistar rats (10mg/kg/day of SIMV) and two control groups (saline) underwent a 21-day treatment period (TP). On the 22nd day one experimental and one control group of rats were sacrificed. Remaining groups of animals were sacrificied on the 32nd day of the study (10-day after-treatment period (AT)). Blood samples and slices of liver, heart, kidney, and brain tissue were obtained for the measurement of PON1 and BuChE activity and levels of MDA. Data were analyzed by means of t-test for independent samples. p values≤0.05 were considered as statistically significant.
  
  
  RESULTS
  SIMV caused a significant decrease of serum and liver PON1 activity (18-24%, p≤0.05) and MDA concentrations in the plasma, heart, liver, kidney, and brain (9-40%, p≤0.05), while plasma and liver BuChE activity increased by 29% (p≤0.05) and 18%, respectively. All effects of SIMV were largely diminished following AT. The exception was MDA, which remained significantly decreased in plasma and all tissues analyzed.
  
  
  CONCLUSIONS
  SIMV significantly decreased PON1 activity and MDA levels and increased BuChE activity. We suggest that the decrease of MDA levels is a beneficial therapeutic effect of SIMV, for example in cardiovascular disorders, while the increase of BuChE activity, especially in brain, may be a potential adverse effect in patients with Alzheimer disease.
authors.affiliation: Department of Pathology and Cytology, University Hospital Center Zagreb, Zagreb, Croatia; Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Macan
authors.affiliation: Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia; Polyclinic Bonifarm, Zagreb, Croatia.
authors.forename: Antonija
authors.initials: A
authors.lastname: Vukšić
authors.affiliation: Institute for Medical Research and Occupational Health, Zagreb, Croatia.
authors.forename: Suzana
authors.initials: S
authors.lastname: Žunec
authors.affiliation: Rudjer Boskovic Institute, NMR Center, Zagreb, Croatia.
authors.forename: Paško
authors.initials: P
authors.lastname: Konjevoda
authors.affiliation: Department of Chemistry and Biochemistry, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Jasna
authors.initials: J
authors.lastname: Lovrić
authors.affiliation: Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Marta
authors.initials: M
authors.lastname: Kelava
authors.affiliation: Rudjer Boskovic Institute, NMR Center, Zagreb, Croatia.
authors.forename: Nikola
authors.initials: N
authors.lastname: Štambuk
authors.affiliation: Faculty of Pharmacy and Biochemistry and Clinical Institute of Chemistry, University Hospital "Sisters of Charity", Zagreb, Croatia.
authors.forename: Nada
authors.initials: N
authors.lastname: Vrkić
authors.affiliation: Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia. Electronic address: vlasta.bradamante@mef.hr.
authors.forename: Vlasta
authors.initials: V
authors.lastname: Bradamante
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D017536:Carotid Artery, Common; D016207:Cytokines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D016328:NF-kappa B; D018696:Neuroprotective Agents; D045162:Thiazolidinediones; D018698:Glutamic Acid; D019821:Simvastatin; D000077205:Pioglitazone
keywords: Butyrylcholinesterase; Malondialdehyde; Paraoxonase 1; Simvastatin