STUDIES ON NEUROBIOCHEMICAL AND NEUROPHARMACOLOGICAL ACTIVITIES IN WISTAR RATS EXPOSED TO ARSENIC WITH OR WITHOUT EXOGENOUS MELATONIN ADMINISTRATION
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Date
2017-08
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KARNATAKA VETERINARY, ANIMAL AND FISHERIES SCIENCES UNIVERSITY, BIDAR
Abstract
(‘As’) induced alterations in neurobiochemestry in brain and its impact on
neuropharmacological activities with or without the melatonin (MLT) as an antioxidant
given exogenously. Male Wistar rats were randomly divided in to four groups of six each.
Group-I served as untreated control, while group-II received ‘As’ [sodium (meta)
arsenite; NaAsO2] @ 10 mg.kg-1 b.wt. (p.o) for a period of 56 days. Experimental rats in
group-III received treatment similar to group-II but in addition received MLT @ 10
mg.kg-1 b.wt. (p.o) from day 32 onwards. Rats in group-IV received MLT alone from day
32 onwards similar to group-III. Sub-chronic exposure to ‘As’ (group-II) significantly
(p0.05)
reduction in pain latency. Sub-chronic administration of ‘As’ induced (group-II)
significant (p<0.05) increase in the levels of thiobarbituric acid reactive substance
(TBARS) called malondialdehyde (MDA) in the brain tissue (5.55±0.57 nmol.g-1), and
their levels were significantly (p<0.05) reduced by MLT supplementation (group-III:
3.96±0.15 nmol.g-1). The increase in 3-nitrotyrosine (3-NT) levels in ‘As’ exposed rats
indicated nitrosative stress due to the formation of peroxynitrite (ONOO-). However,
exogenously given MLT significantly (p<0.05) reduced the 3-NT formation as well as
prostaglandin (PGE2) levels in the brain. Similarly MLT administration have suppressed
the release of pro-inflammatory cytokines (viz., IL-1β, IL-6 & TNF-α) and amyloid-β1-40
(Aβ) deposition in the brain tissues of experimental rats. To conclude, exogenous
administration of melatonin can overcome the sub-chronic arsenic induced oxidative and
nitrosative stress in the CNS, suppressed pro-inflammatory cytokines and restored certain
disturbed neuropharmacological activities in Wistar rats.
Key words: Arsenic (As), Neuropharmacology, Melatonin, Oxidative stress, Wistar rats