Enhanced neuroprotective effect of fish oil in combination with quercetin against 3‐nitropropionic acid induced oxidative stress in rat brain

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2013-01, Vol.40, p.83-92
• Main Authors: Denny Joseph, K.M., Muralidhara
• Format: Article
• Language: English
• Subjects: 3‐Nitropropionic acid; Animals; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Fish oil; Fish Oils - pharmacology; Glutathione - metabolism; Lipid Peroxidation - drug effects; Male; Malondialdehyde - metabolism; Medical sciences; Neuropharmacology; Neuroprotective Agents - pharmacology; Neurotoxicity; Nitro Compounds - pharmacology; Oxidative stress; Oxidative Stress - drug effects; Pharmacology. Drug treatments; Propionates - pharmacology; Quercetin; Quercetin - pharmacology; Rat; Rats; Rats, Wistar
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2012.08.018

While the beneficial effects of fish oil (FO) supplements on the central nervous system function are well established, few findings have led to the hypothesis that long term n–3 polyunsaturated fatty acid (n−3 PUFA) supplements at higher doses render the membranes more susceptible to lipid peroxidation. Hence recent studies suggest the use of dietary antioxidants as adjuncts with n−3 fatty acids to effectively improve the clinical outcome in neurological disorders. In the present investigation, we examined the hypothesis, if enrichment of FO with quercetin (a natural flavonoid) can provide a higher degree of neuroprotection and tested the same in a 3-nitropropionic acid (NPA) rat model. Growing male rats administered with NPA (25mg/kg bw/d, i.p. 4days) were provided either with FO (2mL/kg bw), or Q (25mg/kg bw) or FO+Q for 14days. NPA elicited marked oxidative stress in brain (striatum and cerebellum) as evidenced by significantly enhanced ROS, malondialdehyde, protein carbonyls and nitric oxide levels. Although varying degree of protection was evident among FO or Q groups, complete normalization of oxidative markers ensued only among FO+Q rats. Further, FO+Q combination completely normalized the elevated acetylcholinesterase activity and protected against NPA‐induced mitochondrial dysfunctions. NPA induced depletion of dopamine levels was restored among all groups. Interestingly, NPA induced motor deficits were significantly improved among FO+Q rats. However, further studies are necessary to understand the mechanism/s by which FO enrichment with Q provides higher degree of protection. Nevertheless, our findings clearly suggest that the use of natural phytochemicals with moderate doses of FO may provide better neuroprotection and higher therapeutic advantage in the prevention or treatment of neurodegenerative diseases like Huntington's disease. ► Quercetin (Q) enrichment enhances the neuroprotective effects of fish oil (FO). ► FO+Q attenuate NPA induced oxidative stress and nitric oxide (NO) levels. ► FO+Q normalized AChE activity and restored striatal dopamine levels. ► FO+Q normalized NPA induced mitochondrial dysfunctions. ► FO+Q improved NPA induced motor deficits.