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Molecular and Cellular Biochemistry

, Volume 452, Issue 1–2, pp 199–217 | Cite as

The anxiolytic effects of atorvastatin and simvastatin on dietary-induced increase in homocysteine levels in rats

  • Natasa Mijailovic
  • Dragica Selakovic
  • Jovana Joksimovic
  • Vladimir Mihailovic
  • Jelena Katanic
  • Vladimir JakovljevicEmail author
  • Tamara Nikolic
  • Sergey Bolevich
  • Vladimir Zivkovic
  • Milica Pantic
  • Gvozden Rosic
Article
  • 91 Downloads

Abstract

The aim of this study was to evaluate the effects of atorvastatin and simvastatin on behavioral manifestations that followed hyperhomocysteinemia induced by special dietary protocols enriched in methionine and deficient in B vitamins (B6, B9, B12) by means of alterations in anxiety levels in rats. Simultaneously, we investigated the alterations of oxidative stress markers in rat hippocampus induced by applied dietary protocols. Furthermore, considering the well-known antioxidant properties of statins, we attempted to assess their impact on major markers of oxidative stress and their possible beneficial role on anxiety-like behavior effect in rats. The 4-week-old male Wistar albino rats were divided (eight per group) according to basic dietary protocols: standard chow, methionine-enriched, and methionine-enriched vitamins B (B6, B9, B12) deficient. Each dietary protocol (30 days) included groups with atorvastatin (3 mg/kg/day i.p.) and simvastatin (5 mg/kg/day i.p.). The behavioral testing was performed in the open field and elevated plus maze tests. Parameters of oxidative stress (index of lipid peroxidation, superoxide dismutase, catalase activity, glutathione) were determined in hippocampal tissue samples following decapitation after anesthesia. Methionine-load dietary protocols induced increased oxidative stress in rat hippocampus, which was accompanied by anxiogenic behavioral manifestations. The methionine-enriched diet with restricted vitamins B intake induced more pronounced anxiogenic effect, as well as increased oxidative stress compared to the methionine-load diet with normal vitamins B content. Simultaneous administration of statins showed beneficial effects by means of both decreased parameters of oxidative stress and attenuation of anxiety. The results obtained with simvastatin were more convincible compared to atorvastatin.

Keywords

Homocysteine Atorvastatin Simvastatin Anxiety Oxidative stress Rats 

Abbreviations

Met

Methionine

SAM

S-adenosylmethionine

SAH

S-adenosylhomocysteine

Hcy

Homocysteine

MS

Methionine synthase

GSH

Glutathione

SH

Sulfhydril

SOD

Superoxide dismutase

CAT

Catalase

OF

Open field

EPM

Elevated plus maze

TBARS

Thiobarbituric acid reactive substance

MDA

Malondialdehyde

Notes

Acknowledgements

This work was supported by the Faculty of Medical Sciences (JP 01/13), University of Kragujevac, Serbia.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Natasa Mijailovic
    • 1
  • Dragica Selakovic
    • 1
  • Jovana Joksimovic
    • 1
  • Vladimir Mihailovic
    • 2
  • Jelena Katanic
    • 2
  • Vladimir Jakovljevic
    • 1
    • 3
    Email author
  • Tamara Nikolic
    • 1
  • Sergey Bolevich
    • 3
  • Vladimir Zivkovic
    • 1
  • Milica Pantic
    • 1
  • Gvozden Rosic
    • 1
  1. 1.Department of Physiology, Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia
  2. 2.Department of Chemistry, Faculty of ScienceUniversity of KragujevacKragujevacSerbia
  3. 3.Department of Human Pathology1st Moscow State Medical University IM SechenovMoscowRussia

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