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

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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.

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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

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Acknowledgements

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

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac, 34000, Serbia

    Natasa Mijailovic, Dragica Selakovic, Jovana Joksimovic, Vladimir Jakovljevic, Tamara Nikolic, Vladimir Zivkovic, Milica Pantic & Gvozden Rosic

  2. Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovica 12, Kragujevac, 34000, Serbia

    Vladimir Mihailovic & Jelena Katanic

  3. Department of Human Pathology, 1st Moscow State Medical University IM Sechenov, Moscow, Russia

    Vladimir Jakovljevic & Sergey Bolevich

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  1. Natasa Mijailovic
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  2. Dragica Selakovic
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  4. Vladimir Mihailovic
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Correspondence to Vladimir Jakovljevic.

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Mijailovic, N., Selakovic, D., Joksimovic, J. et al. The anxiolytic effects of atorvastatin and simvastatin on dietary-induced increase in homocysteine levels in rats. Mol Cell Biochem 452, 199–217 (2019). https://doi.org/10.1007/s11010-018-3425-6

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