Naringin attenuates Bisphenol-A mediated neurotoxicity in hypertensive rats by abrogation of cerebral nucleotide depletion, oxidative damage and neuroinflammation

• Published in: Neurotoxicology (Park Forest South) 2020-12, Vol.81, p.18-33
• Main Authors: Akintunde, J.K., Akintola, T.E., Adenuga, G.O., Odugbemi, Z.A., Adetoye, R.O., Akintunde, O.G.
• Format: Article
• Language: English
• Subjects: Apoptosis; ATP hydrolysis; Bisphenol-A; L-NAME; Naringin; neuro-inflammation
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2020.08.001

[Display omitted] •BPA mediates neurotoxicity in hypertensive rats.•BPA increases motor coordination-linked behaviour in hypertensive rats.•BPA up-regulates proinflammatory mediators in hypertensive rats.•BPA increases antigen presenting cell and T-killer CD43 cell in hypertensive rats.•Naringin attenuates BPA-mediated neurotoxicity in hypertensive rat model. We examined whether active fruit naringin can reduce the risk of BPA-mediated neurotoxicity in L-NAME induced hypertensive rats and whether the modulation could be linked to improvement of brain NO signaling. Male albino rats were randomly distributed into eight (n = 7) groups. Group I was control animals, Group II was orally-treated with L-NAME, Group III was orally treated with 100 mg/kg BPA, Group IV was orally-treated with L-NAME +100 mg/kg BPA. Group V was orally-administered with L-NAME +80 mg/kg NAR. Group VI was orally-administered with 100 mg/kg BPA +80 mg/kg NAR. Group VII was orally-administered with L-NAME+100 mg/kg BPA +80 mg/kg NAR. Lastly, group VIII was orally-treated with 80 mg/kg NAR. The treatment lasted for 14 days. Sub-acute exposure to L-NAME and BPA induced hypertension and mediated-neuroinflammation at CA-2 and CA-4 of hippocampus cells. It was evident by increase in PDE-51 and enzymes of ATP hydrolysis (ATPase, ADPase and AMPase) with corresponding upsurge in cholinergic (AChE and BuChE), dopaminergic (MAO-A) and adenosinergic (ADA) enzymes as well as movement disorder. The hypertensive-mediated neurotoxicity was related to alteration of NO signaling and higher release of pro-inflammatory cytokines (TNF-α and IL-1β), apoptotic proteins (P53 and caspace-9) and facilitated entry of T-lymphocytes (CD43+) into CNS through blood brain barrier potentiated by antigen presenting cells. Hence, these features of BPA-mediated neurotoxicity in L-NAME induced hypertensive rats were prohibited by co-administration of NAR through production of neuro-inflammatory mediators, stabilizing neurotransmitter enzymes, normalizing NO signaling and improving brain histology.