Involvement of the nitric oxide signaling in modulation of naringin against intranasal manganese and intracerbroventricular β-amyloid induced neurotoxicity in rats

Abstract

Manganese -induced aggregation of the amyloid-β peptide (Aβ) is a hallmark molecular feature of Alzheimer's disease (AD). The current study was designed to investigate the effects of chronic administration of naringin against β-A1–42 and manganese induced experimental model. Wistar rats received intracerebroventricular (ICV) β-A1–42 once, intranasal manganese, naringin and nitric oxide modulators for 21 days and behavioral alterations were assessed. Mitochondrial enzymes, oxidative parameters, TNF-α, β-A1–42 acetylcholinesterase (AChE) levels and manganese concentration were measured. ICV β-A1–42 and intranasal manganese treated rats showed a memory deficit and significantly increased in β-A1–42 level and manganese concentration, mitochondrial oxidative damage, AChE level and inflammatory mediator in the hippocampus and cortex. Chronic administration of naringin (40 and 80 mg/kg) significantly improved memory performance and attenuated the oxidative damage and mitochondrial dysfunction in Aβ with Mn treated rats. In addition, naringin also attenuates the pro-inflammatory cytokines like TNF-α, AChE, Amyloid deposition and Mn concentration. Further, pretreatment of N(G)-Nitro-L-arginine methyl ester (L-NAME) with (5 mg/kg) with lower dose of naringin significantly potentiated its protective effect. These results demonstrate that naringin offers protection against ICV β-A1–42 and intranasal manganese induced memory dysfunction possibly due to its antioxidant, anti-inflammatory, anti-amyloidogenesis therefore, could have a therapeutic potential in Alzheimer's disease.