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Modulatory mechanisms of copper II -albumin complex toward N-nitrosodiethylamine-induced neurotoxicity in mice via regulating oxidative damage, inflammatory, and apoptotic signaling pathways

Research Authors
Obeid Shanab a, Laila Mostafa a, Ahmed Abdeen b, Rania Atia c d, Ahmed Y. Nassar e, Mohammed Youssef f, Samah F. Ibrahim g, Zainab M. Maher h, Florin Imbrea i, Liana Fericean j, Khaled Ghareeb k, Tabinda Hasan l, Heba I. Ghamry m, Reem T. Atawia n, Omar S
Research Date
Research Department
Research Journal
Ecotoxicology and Environmental Safety
Research Member
Research Publisher
Elsevier
Research Vol
720
Research Website
https://www.sciencedirect.com/science/article/pii/S0147651323013453?via%3Dihub
Research Year
2024
Research_Pages
115841
Research Abstract

N-nitrosodiethylamine (ND) is an extremely toxic unavoidable environmental contaminant. CopperII-albumin (CuAB) complex, a newly developed Cu complex, showed antioxidant and anti-inflammatory potential. Hereby, we explored the plausible neuroprotective role of CuAB complex toward ND-evoked neurotoxicity in mice. Twenty-four male mice were sorted into 4 groups (6 mice each). Control group, mice were administered oral distilled water; and CuAB group, mice received CuAB complex at a dose of 817 µg/kg orally, three times weekly. In ND group, ND was given intraperitoneally (50 mg/kg body weight, once weekly for 6 w). CuAB+ND group, mice were administered a combination of CuAB and ND. The brain was quickly extracted upon completion of the experimental protocol for the evaluation of the oxidative/antioxidative markers, inflammatory cytokines, and histopathological examination. Oxidative stress was induced after ND exposure indicated by a reduction in GSH and SOD1 level, with increased MDA level. In addition, decreased expression of SOD1 proteins, Nrf2, and 5-HT mRNA expression levels were noticed. An apoptotic cascade has also been elicited, evidenced by overexpression of Cyt c, Cl. Casp 3. In addition, increased regulation of proinflammatory genes (TNF-α, IL-6, iNOS, Casp1, and NF-κB (p65/p50); besides, increment of protein expression of P-IKBα and reduced expression of IKBα. Pretreatment with CuAB complex significantly ameliorated ND neuronal damage. Our results recommend CuAB complex supplementation because it exerts neuroprotective effects against ND-induced toxicity.