engleski

The Dual Nature of the Antiepileptic Drug Valproic Acid

Valproic acid (VPA) is a short fatty acid with strong anticonvulsant properties. It has diverse effec ts in different tissues with opposing mechanisms of physiological action. Due to the effects on energy, fatty acid, and cholesterol metabolism, it may be a risk factor for the development of diabetes with its associated complications of atherosclerosis, we ight gain, hypertension, insulin resistance and other complications. Its negative effects on the endocrine system can have severe health consequences, especially in the female population. VPA produces proinflammatory and proapoptotic effects in the liver a nd anti - inflammatory and antiapoptotic effects in the central nervous system. It also causes abnormalities in lipid and cholesterol transport in the liver and the reproductive organs, while in neural stem cells it decreases cholesterol accumulation and hel ps neural growth and differentiation. However, in the CNS it has some beneficial effects, which are proposed to be important in Alzheimer’s disease (AD). In AD mouse models, VPA exerted antiapoptotic effects and the expression of transcription factors that promote neurite growth. Most of the adverse pathogenic actions or beneficial molecular effects are not fully understood. We present an overview and comparison of the different properties of VPA and their effects on estrogen and cholesterol metabolism, lip id transport, Alzheimer’s disease, and on the physiology of the liver, reproductive organs, and neurons from in vitro and in vivo (in animal models and patients) studies.

hepatotoxicity, metabolic disorders, lipid transport, steroidogenesis, Alzheimer’s disease

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