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Hyperlipidemia Downregulate Brain Antioxidant Defense Enzymes and Neurotrophins in Rats: Assessment of the Modulatory Potential of EPA+DHA and Zerumbone
Author(s) -
Uppin Vinayak,
Acharya Pooja,
Bettadaiah Bheemanakere Kempaiah,
Talahalli Ramaprasad Ravichandra
Publication year - 2020
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202000381
Subject(s) - hyperlipidemia , antioxidant , eicosapentaenoic acid , brain derived neurotrophic factor , oxidative stress , chemistry , endocrinology , medicine , docosahexaenoic acid , pharmacology , downregulation and upregulation , monoamine oxidase , nadph oxidase , neurotrophic factors , lipid peroxidation , biochemistry , enzyme , polyunsaturated fatty acid , fatty acid , receptor , gene , diabetes mellitus
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.