Alpha-Asarone attenuates alcohol-induced hepatotoxicity in a murine model by ameliorating oxidative stress, inflammation, and modulating apoptotic-Autophagic cell death.

Autor: Ali NAM; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt., Abdelhamid AM; Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt., El-Sayed NM; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt., Radwan A; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt. Electronic address: asmaa_elsayed@pharm.suez.edu.eg.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2024 Sep; Vol. 490, pp. 117041. Date of Electronic Publication: 2024 Jul 24.
DOI: 10.1016/j.taap.2024.117041
Abstrakt: Alcoholic liver disease (ALD) is a major cause of chronic liver injury characterized by steatosis, inflammation, and fibrosis. This study explored the hepatoprotective mechanisms of alpha-asarone in a mouse model of chronic-binge alcohol feeding. Adult male mice were randomized into control, alcohol, and alcohol plus alpha-asarone groups. Serum aminotransferases and histopathology assessed liver injury. Oxidative stress was evaluated via malondialdehyde content, glutathione, superoxide dismutase, and catalase activities. Pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were quantified by ELISA. P53-mediated apoptosis was determined by immunohistochemistry. Key autophagy markers phospho-AMPK, AMPK, Beclin-1, LC3-I/LC3-II ratio, and LC3 were examined by immunoblotting. Alcohol administration increased serum ALT, AST and ALP, indicating hepatocellular damage. This liver dysfunction was associated with increased oxidative stress, inflammation, p53 expression and altered autophagy. Alpha-asarone treatment significantly decreased ALT, AST and ALP levels and improved histological architecture versus alcohol alone. Alpha-asarone also mitigated oxidative stress, reduced TNF-α, IL-1β and IL-6 levels, ameliorated p53 overexpression and favorably modulated autophagy markers. Our findings demonstrate that alpha-asarone confers protective effects against ALD by enhancing antioxidant defenses, suppressing hepatic inflammation, regulating apoptotic signaling, and restoring autophagic flux. This preclinical study provides compelling evidence for the therapeutic potential of alpha-asarone in attenuating alcohol-induced liver injury and warrants further evaluation as a pharmacotherapy for ALD.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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