Curcumin and Nano-Curcumin Mitigate Copper Neurotoxicity by Modulating Oxidative Stress,Inflammation, and Akt/GSK-3β Signaling |
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Authors: | Wedad S Sarawi Ahlam M Alhusaini Laila M Fadda Hatun A Alomar Awatif B Albaker Amjad S Aljrboa Areej M Alotaibi Iman H Hasan Ayman M Mahmoud |
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Institution: | 1.Pharmacology and Toxicology Department, Faculty of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (W.S.S.); (A.M.A.); (L.M.F.); (H.A.A.); (A.B.A.); (A.S.A.); (A.M.A.); (I.H.H.);2.Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia;3.Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt |
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Abstract: | Copper (Cu) is essential for multiple biochemical processes, and copper sulphate (CuSO4) is a pesticide used for repelling pests. Accidental or intentional intoxication can induce multiorgan toxicity and could be fatal. Curcumin (CUR) is a potent antioxidant, but its poor systemic bioavailability is the main drawback in its therapeutic uses. This study investigated the protective effect of CUR and N-CUR on CuSO4-induced cerebral oxidative stress, inflammation, and apoptosis in rats, pointing to the possible involvement of Akt/GSK-3β. Rats received 100 mg/kg CuSO4 and were concurrently treated with CUR or N-CUR for 7 days. Cu-administered rats exhibited a remarkable increase in cerebral malondialdehyde (MDA), NF-κB p65, TNF-α, and IL-6 associated with decreased GSH, SOD, and catalase. Cu provoked DNA fragmentation, upregulated BAX, caspase-3, and p53, and decreased BCL-2 in the brain of rats. N-CUR and CUR ameliorated MDA, NF-κB p65, and pro-inflammatory cytokines, downregulated pro-apoptotic genes, upregulated BCL-2, and enhanced antioxidants and DNA integrity. In addition, both N-CUR and CUR increased AKT Ser473 and GSK-3β Ser9 phosphorylation in the brain of Cu-administered rats. In conclusion, N-CUR and CUR prevent Cu neurotoxicity by attenuating oxidative injury, inflammatory response, and apoptosis and upregulating AKT/GSK-3β signaling. The neuroprotective effect of N-CUR was more potent than CUR. |
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Keywords: | curcumin GSK-3β inflammation DNA damage oxidative stress |
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