Neuroprotective efficacy of a combination of fish oil and ferulic acid against 3-nitropropionic acid-induced oxidative stress and neurotoxicity in rats: behavioural and biochemical evidence

FO supplementation at higher doses for longer duration is likely to cause oxidative stress in vivo. To overcome this,
attempts have been made to enrich FO with known antioxidants/phytochemicals. In the present study, we examined the
hypothesis that a combination of FO with ferulic acid (FA), a naturally occurring phenolic compound, is likely to provide higher
degree of neuroprotection. This was examined by employing 3-nitropropionic acid (NPA), a well-known neurotoxin used to
mimic behavioural and neurochemical features of Huntington’s disease. Growing male rats administered with NPA (25 mg/kg of
body weight (bw) for 4 days) were provided with either FO (2 mL/kg bw), FA (50 mg/kg bw) or FO+FA for 2 weeks. Interestingly,
FO+FA not only offered significant protection against NPA-induced behavioural impairments, but also markedly attenuated
oxidative stress in brain regions (striatum/cerebellum) as evidenced by the reduction in reactive species, malondialdehyde,
hydroperoxides and nitric oxide (NO) levels. Further, FO+FA combination restored the activities of various antioxidant enzymes
and the levels of cytosolic calcium. In striatum, activity levels of acetylcholinesterase enzyme and dopamine levels were
markedly restored among FO+FA rats. Interestingly, NPA-induced mitochondrial dysfunctions were also attenuated among
FO+FA rats. Collectively, our findings suggest the advantage of co-treatment of FO with known antioxidants to achieve a higher
therapeutic benefit in the treatment of oxidative stress-mediated neurodegenerative conditions.