Hyperlipidemia Downregulate Brain Antioxidant Defense Enzymes and Neurotrophins in Rats: Assessment of the Modulatory Potential of EPA plus DHA and Zerumbone

摘要

Background Oxidative stress (OS) plays a vital role in the pathogenesis of cognitive disorders. In this study, brain antioxidant defense dysregulation as a consequence of hyperlipidemia, and the efficacy of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), and zerumbone (Z) in their modulation are assessed. Methods and results Male Wistar rats are fed control, high-fat (HF), HF + fish oil (HF+F), HF + zerumbone (HF+Z), and HF + fish oil + zerumbone (HF+F+Z) diet for 60 days. Markers of OS, antioxidant enzymes, monoamine oxidase, nuclear factor (erythroid-derived 2)-like 2 (NRF-2), nitric oxide-2 (NOS-2), inter cellular adhesion molecule-1 (ICAM-1), and neurotrophins are measured. Hyperlipidemia increases OS, decreases antioxidant enzyme activity, increases monoamine oxidase activity, increases NOS-2 and ICAM-1 expression, decreases NRF-2 activation, decreases nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) levels in the brain compared to control. While EPA+DHA and zerumbone significantly (p< 0.05) restores the perturbations induced by hyperlipidemia. Conclusion It is concluded that hyperlipidemia cause OS by decreasing the activity of brain antioxidant enzymes via the downregulation of NRF-2. The reduced brain neurotrophins in hyperlipidemia indicate its potential risk on cognitive attributes. EPA+DHA, together with zerumbone, positively modulates hyperlipidemia induced brain dysfunction thereby offering promising therapeutic strategy.