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Ecotoxicol Environ Saf ; 270: 115841, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38113799

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.


Subject(s)
Copper , Neurotoxicity Syndromes , Mice , Male , Animals , Copper/toxicity , Diethylnitrosamine/pharmacology , Superoxide Dismutase-1/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Oxidative Stress , Signal Transduction , Antioxidants/pharmacology , Antioxidants/metabolism , Neurotoxicity Syndromes/drug therapy , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/prevention & control , NF-E2-Related Factor 2/metabolism
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