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

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
(25 mg/kg bw/d, i.p. 4 days) were provided either with FO (2 mL/kg bw), or Q (25 mg/kg bw) or FO+Q
for 14 days. 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.