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Effects of Low- and High-Dose Valproic Acid and Lamotrigine on the Heart in Female Rats

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Abstract

Epilepsy is a chronic neurological disease that affects more than 50 million people worldwide. Antiepileptic drugs (AEDs) are the mainstay of treatment for most patients with epilepsy. However, AEDs have been reported to be associated with adverse cardiac effects. In this study, it was aimed to investigate the possible cardiac effects of low-dose (LD) and high-dose (HD) treatment of valproic acid (VPA) and lamotrigine (LTG), which are commonly used AEDs, in rats without epilepsy. Rats were randomly grouped as control, LD-VPA, HD-VPA, LD-LTG, and HD-LTG. The cardiac effects of AEDs were evaluated using immunohistological, biochemical, and hemodynamic parameters. A dose-dependent increase in the intensity of caspase-3 staining was detected in the VPA and LTG groups. The intensity of connexin-43 and troponin-T staining in the VPA groups and desmin staining in the LTG groups was significantly reduced. Biochemically, HD-VPA and HD-LTG administrations caused a significant increase in MDA level in myocardial tissue. In addition, as a result of hemodynamic evaluations, cardiac functions were found to be affected and blood pressure increased in HD-LTG group. The results of present study support that VPA and LTG treatment can increase cardiac risk markers.

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Authors and Affiliations

  1. Department of Histology and Embriyology, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey

    Azibe Yıldız & Nigar Vardı

  2. Department of Medical Pharmacology, Faculty of Medicine, Inonu University, Malatya, Turkey

    Hakan Parlakpınar

  3. Department of Chemistry, Faculty of Arts and Sciences, Inonu University, Malatya, Turkey

    Burhan Ateş

  4. Department of Histology and Embriyology, Faculty of Medicine, Firat University, Elazig, Turkey

    Neriman Çolakoğlu

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  1. Azibe Yıldız
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Yıldız, A., Vardı, N., Parlakpınar, H. et al. Effects of Low- and High-Dose Valproic Acid and Lamotrigine on the Heart in Female Rats. Cardiovasc Toxicol 22, 326–340 (2022). https://doi.org/10.1007/s12012-021-09714-6

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