Melatonin Ameliorates Neuropharmacological and Neurobiochemical Alterations Induced by Subchronic Exposure to Arsenic in Wistar Rats

Abstract

An experimental study was conducted in Wistar rats to characterize the arsenic ("As")-induced alterations in neurobiochemistry 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] at 10 mg/kg bw (p.o.) for a period of 56 days. Experimental rats in group III received treatment similar to group II but in addition received MLT at 10 mg/kg bw (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 reduced both voluntary locomotor and forced motor activities and melatonin supplementation (group III) showed a significant improvement in motor activities, when subjected to test on day 42 or 56. Rats exposed to As showed a significant increase in anxiety level and a marginal nonsignificant reduction in pain latency. Sub-chronic administration of As induced (group II) significant 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 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 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, and TNF-α) and amyloid-β_1–40 (Aβ) deposition in the brain tissues of experimental rats. To conclude, exogenous administration of melatonin can overcome the sub-chronic As-induced oxidative and nitrosative stress in the CNS, suppressed pro-inflammatory cytokines, and restored certain disturbed neuropharmacological activities in Wistar rats.

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