Curcumin and nano-curcumin mitigate copper neurotoxicity by modulating oxidative stress, inflammation, and akt/gsk-3β signaling

Sarawi, Wedad S, Alhusaini, Ahlam M, Fadda, Laila M, Alomar, Hatun A, Albaker, Awatif B, Aljrboa, Amjad S, Alotaibi, Areej M, Hasan, Iman H and Mahmoud, Ayman M ORCID: https://orcid.org/0000-0003-0279-6500 (2021) Curcumin and nano-curcumin mitigate copper neurotoxicity by modulating oxidative stress, inflammation, and akt/gsk-3β signaling. Molecules, 26 (18). 5591. ISSN 1420-3049

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Official URL: http://dx.doi.org/10.3390/molecules26185591

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.

Item Type:	Article (Article)
Peer-reviewed:	Yes
Date Deposited:	16 May 2024 11:01
Publisher:	MDPI AG
Additional Information:	This is an open access article which first appeared in Molecules, published by MDPI
Divisions:	Faculties > Science and Engineering
Subject terms:	Brain, Animals, Rats, Rats, Wistar, Copper, Curcumin, Tumor Necrosis Factor-alpha, NF-kappa B, Anti-Inflammatory Agents, Interleukin-6, Antioxidants, Signal Transduction, Apoptosis, Oxidative Stress, Male, Proto-Oncogene Proteins c-akt, Nanoparticles, Glycogen Synthase Kinase 3 beta, Heavy Metal Poisoning, DNA damage, GSK-3β, curcumin, inflammation, oxidative stress, Animals, Anti-Inflammatory Agents, Antioxidants, Apoptosis, Brain, Copper, Curcumin, Glycogen Synthase Kinase 3 beta, Heavy Metal Poisoning, Interleukin-6, Male, NF-kappa B, Nanoparticles, Oxidative Stress, Proto-Oncogene Proteins c-akt, Rats, Rats, Wistar, Signal Transduction, Tumor Necrosis Factor-alpha, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 0307 Theoretical and Computational Chemistry, Organic Chemistry
Data Access Statement:	Data analysed or generated during this study are included in this manuscript.
URI:	https://e-space.mmu.ac.uk/id/eprint/634654
DOI:	https://doi.org/10.3390/molecules26185591
ISSN	1420-3049
e-ISSN	1420-3049

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