N-salicyloyl tryptamine derivatives as potential therapeutic agents for doxorubicin-induced hepatotoxicity via PI3K/AKT/HO-1 signaling pathway
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Le résumé fourni par la source
Doxorubicin (DOX) is a broad-spectrum antineoplastic agent with remarkable efficacy against various malignant tumors. However, its clinical application is severely limited by profound hepatotoxicity, wherein oxidative stress acts as a pivotal mechanism underlying DOX-induced hepatotoxicity. N -salicyloyl tryptamine derivatives (NSTs) have been reported to possess potent antioxidant activities. In the present study, NSTs were applied for the first time in DOX-induced hepatotoxicity with structural modifications to the scaffold. Through systematic screening, a novel compound A50 was identified as the most potent active candidate. Both in vitro (AML12 cell lines) and in vivo (mice model of DOX-induced hepatotoxicity) experiments demonstrated that A50 significantly enhanced superoxide dismutase (SOD) activity, reduced malondialdehyde (MDA) levels, stabilized mitochondrial membrane potential (MMP), and promoted adenosine triphosphate (ATP) production, thus effectively improving mitochondrial function and suppressing oxidative stress-mediated damage. Additionally, A50 decreased serum levels of liver injury biomarkers [alanine transaminase (ALT), aspartate transaminase (AST) and levels of proinflammatory cytokines [tumor necrosis factor-αα (TNF-α), interleukin-6 (IL-6)], inhibited lactate dehydrogenase (LDH) activity, and attenuated histopathological lesions in liver tissues, without affecting its anti-hepatocellular carcinoma activity. Mechanism investigations revealed the hepatoprotective effects of A50 were associated with activation of the PI3K/AKT/HO-1 signaling pathway, and these effects could be blocked by the PI3K-specific inhibitor LY294002 in vitro. In conclusion, A50 may alleviated DOX-induced hepatotoxicity by activating the PI3K/AKT/HO-1 pathway to inhibit oxidative stress-driven pathological processes, including mitochondrial dysfunction, inflammation, and apoptosis. These findings highlight A50 as a promising candidate for the treatment of DOX-induced hepatotoxicity.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- N-salicyloyl tryptamine derivatives as potential therapeutic agents for doxorubicin-induced hepatotoxicity via PI3K/AKT/HO-1 signaling pathway
- Date Crossref
- 24/09/2026
- Éditeur
- Frontiers Media SA
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of South China Department of Thoracic and Cardiovascular Surgery pays non établi dans la noticeUniversité ou école supérieure
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Gansu University of Traditional Chinese Medicine pays non établi dans la noticeUniversité ou école supérieure
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Gansu Provincial Hospital Department of General Surgery pays non établi dans la noticeÉtablissement de santé
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First Affiliated Hospital of University of South China pays non établi dans la noticeÉtablissement de santé
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Hengyang Academy of Agricultural Sciences pays non établi dans la noticeStructure de recherche
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Institute of Tibetan Plateau Research pays non établi dans la noticeStructure de recherche
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Hunan Provincial Maternal and Child Health Hospital pays non établi dans la noticeÉtablissement de santé
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School of Basic Medicine pays non établi dans la noticeUniversité ou école supérieure
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The First Clinical Medical College of Gansu University of Chinese Medicine pays non établi dans la noticeUniversité ou école supérieure
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Hengyang Traditional Chinese Medicine Hospital pays non établi dans la noticeÉtablissement de santé
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National Health Commission Key Laboratory of Birth Defect Research and Prevention Hunan Provincial Maternal and Child Healthcare Hospital pays non établi dans la noticeStructure de recherche
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Qinghai Provincial Key Laboratory of Tibetan Medicine Research pays non établi dans la noticeStructure de recherche
Department of Thoracic and Cardiovascular Surgery — University of South China, Gansu University of Traditional Chinese Medicine et Department of General Surgery — Gansu Provincial Hospital, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.