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

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