Infliximab and/or MESNA alleviate doxorubicin-induced Alzheimer's disease-like pathology in rats: A new insight into TNF-α/Wnt/β-catenin signaling pathway.

Autor: Mohamad HE; Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt., Abo-Elmatty DM; Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt., Wahba NS; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt., Shaheen MA; Department of Histology and Cell Biology, Faculty of Human Medicine, Zagazig University, Zagazig 44519, Egypt., Sakr RT; Medical Administration, Zagazig University, Zagazig 44519, Egypt., Wahba AS; Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt. Electronic address: alaa.samir@pharm.suez.edu.eg.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2022 Jul 15; Vol. 301, pp. 120613. Date of Electronic Publication: 2022 May 03.
DOI: 10.1016/j.lfs.2022.120613
Abstrakt: Aims: The current study aimed to elucidate the neurotoxic potential of DOX to induce AD-like pathology paying attention to the role of wingless-integrated/β-catenin (Wnt/β-catenin) signaling pathway. A major aim was to evaluate the efficacy of infliximab (IFX) either individually or in combination with 2-mercaptoethane sulfonate sodium (MESNA) on the DOX-induced neurotoxicity in rats.
Methodology: AD-like pathology was induced in adult male Wistar rats by intraperitoneal (i.p.) administration of DOX at a dose of 3.5 mg/kg twice a week for 3 weeks. DOX-injected rats were then treated with either INF at a single dose of 5 mg/kg i.p. (IFX group), MESNA at a dose of 160 mg/kg/day i.p. for 4 weeks (MESNA group) or their combination at the same specified doses (INF + MESNA group). At the end of the study period, behavioral assessment was performed and the brain tissue samples were harvested at sacrifice.
Key Findings: DOX-treated rats significantly exhibited AD-like brain injury, increased amyloid burden, enhanced neuroinflammation and apoptosis, and multifocal histological injury in the cerebral cortex with widespread vacuolations. IFX and MESNA significantly reversed all the aforementioned detrimental effects in the DOX-treated rats.
Significance: The study has provided sufficient evidence of the potential of IFX and/or MESNA to ameliorate the DOX-induced neurotoxicity, with the best improvement observed with their combined administration. A new insight has been introduced into the critical role of Wnt/β-catenin activation.
(Copyright © 2022. Published by Elsevier Inc.)
Databáze: MEDLINE
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