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Interactive Neuroprotective Strategies Employing Phytochemicals and Omega-3 Fatty Acids.

Denny Joseph, K.M. (2013) Interactive Neuroprotective Strategies Employing Phytochemicals and Omega-3 Fatty Acids. PhD thesis, University of Mysore.

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Abstract

Fish and fish oil (FO) constitute a rich source of n-3 polyunsaturated fatty acids (n-3 PUFA), Eicosapentaenoic acid (EPA, 20:5n-3) and Docosahexaenoic acid (DHA). FO dietary supplements have been gaining popularity in recent years due to various health benefits provided by the PUFA. Epidemiological studies suggest that consumption of more n-3 PUFA may reduce the risk for a variety of diseases including cardiovascular, neurological and immunological disorders, diabetes and cancer. In animal models, FO supplementation is shown to prevent cognitive decline and memory impairments and enhanced reference and working memory performance. Surprisingly, very few studies have assessed the neuroprotective effect of either n-3 PUFA or FO in animal models of neurotoxicity. Previously high dietary intake of n-3 PUFA was shown to exert robust neuroprotective action in an animal model of Parkinsonism. In a recent study, chronic (70 days) FO supplementation (4 g/ kg bw/ d) was demonstrated to significantly offset both behavioral and neurochemical alterations in a 6-hydroxydopamine model of Parkinson’s disease (PD). Besides these studies, no comprehensive data exists on the propensity of FO prophylaxis to render neuroprotection under experimentally -induced neurotoxicity. The primary focus of the thesis was to understand whether FO supplements can render protection against neurotoxicant- induced oxidative stress, mitochondrial dysfunctions and neurotoxicity. Two neurotoxins viz., rotenone (ROT) and 3-nitropropionic acid (NPA) were employed. The salient findings obtained revealed that FO supplementation among both growing and old rats has the propensity to protect against neurotoxin -induced early oxidative stress and mitochondrial dysfunctions and neurotoxicity. Based on evidence obtained in two neurotoxin models, it is hypothesized that the neuroprotective efficacy of FO may be predominantly due to its ability to enhance the GSH levels, attenuation of compromised antioxidant status in specific regions of the brain and decreased protein oxidation. Further, it may also be related to its ability to restore cholinergic function, preserve the mitochondrial metabolic state and, integrity of ETC enzymes. These findings give further credence to the existing neuroprotective role of FO and favor its usage as a therapeutic adjuvant to protect brain against neurodegenerative disorders exhibiting enhanced oxidative stress conditions. Although several evidence demonstrate the beneficial effects of FO supplements, few experimental findings highlight that dietary n-3 PUFA at ‘high doses’ and ‘long duration’ render the membrane more susceptible to lipid peroxidation. Hence recently attempts have been made to enhance the neuroprotective efficacy of FO by fortification with antioxidants/ phytochemicals. Accordingly another major question addressed in this thesis is related to the enhancement of neuroprotective efficacy by enrichment of FO with Quercetin (Q), (one of the most widely distributed flavonoids in plants). The combined efficacy of FO + Q was investigated in SH-SY5Y cell and in vivo models. The neuroprotective efficacy of FO + Q combination was assessed in terms of its potency to attenuate NPA induced oxidative stress in cytosol/ mitochondria, mitochondrial dysfunctions and locomotor deficits. Data obtained clearly demonstrate that enrichment of lower dose of FO with Q provides a higher degree of neuroprotection in NPA model of HD. It is speculated that FO and Q may be affecting different steps or pathways in the NPA cascade resulting in improved protection. These findings add further credence to the fact that incorporation of Q or natural antioxidants to FO or fish products can be of great therapeutic importance in the prevention and treatment of neurodegenerative diseases exhibiting enhanced oxidative stress. Further, in a similar approach the neuroprotective efficacy of a combination of FO with Bacopa monnieri (BM) (a well-known phytomedicine) was also investigated in chemical models of neurotoxicity. The efficacy of FO + BM combination was more pronounced in striatum among both NPA and ROT models as evidenced by behavioral, biochemical and neurochemical parameters. These findings clearly highlight the benefits of a combination of FO with BM extract. The combination offered significant protection against both behavioral and biochemical alterations induced by neurotoxins among both growing and old rats.

Item Type: Thesis (PhD)
Uncontrolled Keywords: neurotoxicity, Fish Oil supplementation, health benefits
Subjects: 500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 17 Fatty Acid Chemistry
Divisions: Dept. of Biochemistry
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 17 Mar 2015 11:05
Last Modified: 17 Mar 2015 11:05
URI: http://ir.cftri.com/id/eprint/11753

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