Stimulation of Autophagy by Dapagliflozin Mitigates Cadmium-Induced Testicular Dysfunction in Rats: The Role of AMPK/mTOR and SIRT1/Nrf2/HO-1 Pathways
Rattachement africain : Égypte, sa, ae. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Cadmium (Cd) is a widespread environmental pollutant that triggers testicular dysfunction. Dapagliflozin is a selective sodium-glucose co-transporter-2 inhibitor with notable antioxidant and anti-apoptotic features. It has shown marked cardio-, reno-, hepato-, and neuroprotective effects. Yet, its effect on Cd-evoked testicular impairment has not been examined. Hence, the goal of the current study was to investigate the potential positive effect of dapagliflozin against Cd-induced testicular dysfunction in rats, with an emphasis on autophagy, apoptosis, and oxidative insult. Dapagliflozin (1 mg/kg/day) was given by oral gavage, and testicular dysfunction, impaired spermatogenesis, and biomolecular events were studied via immunohistochemistry, histopathology, and ELISA. The current findings demonstrated that dapagliflozin improved relative testicular weight, serum testosterone, and sperm count/motility and reduced sperm abnormalities, signifying mitigation of testicular impairment and spermatogenesis disruption. Moreover, dapagliflozin attenuated Cd-induced histological abnormalities and preserved testicular structure. The testicular function recovery was prompted by stimulating the cytoprotective SIRT1/Nrf2/HO-1 axis, lowering the testicular oxidative changes, and augmenting cellular antioxidants. As regards apoptosis, dapagliflozin counteracted the apoptotic machinery by downregulating the pro-apoptotic signals together with Bcl-2 upregulation. Meanwhile, dapagliflozin reactivated the impaired autophagy, as seen by a lowered accumulation of SQSTM-1/p62 and Beclin 1 upregulation. In the same context, the testicular AMPK/mTOR pathway was stimulated as evidenced by the increased p-AMPK (Ser487)/total AMPK ratio alongside the lowered p-mTOR (Ser2448)/total mTOR ratio. Together, the favorable mitigation of Cd-induced testicular impairment/disrupted spermatogenesis was driven by the antioxidant, anti-apoptotic, and pro-autophagic actions of dapagliflozin. Thus, it could serve as a tool for the management of Cd-evoked testicular dysfunction.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Stimulation of Autophagy by Dapagliflozin Mitigates Cadmium-Induced Testicular Dysfunction in Rats: The Role of AMPK/mTOR and SIRT1/Nrf2/HO-1 Pathways
- Date Crossref
- 14/07/2023
- Éditeur
- MDPI AG
- 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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Cairo University Cairo University, Égypte (code pays fourni par la source)Université ou école supérieure
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Taif University pays non établi dans la noticeUniversité ou école supérieure
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National Organization for Drug Control and Research Égypte (code pays fourni par la source)Structure de recherche
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Egyptian Government Égypte (code pays fourni par la source)Organisme public
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Egyptian Drug Authority Department of Pharmacology Giza, Égypte (code pays fourni par la source)Organisme public
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Umm al-Qura University pays non établi dans la noticeUniversité ou école supérieure
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Princess Nourah bint Abdulrahman University pays non établi dans la noticeUniversité ou école supérieure
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King Saud University pays non établi dans la noticeUniversité ou école supérieure
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Gulf Medical University pays non établi dans la noticeUniversité ou école supérieure
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Faculty of Pharmacy Department of Biochemistry Cairo University, Égypte (pays nommé en fin d’affiliation)Université ou école supérieure
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College of Pharmacy Department of Pharmacology and Toxicology pays non établi dans la noticeUniversité ou école supérieure
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College of Medicine Basic Health Sciences Department pays non établi dans la noticeUniversité ou école supérieure
Cairo University (Cairo University, Égypte), Taif University et National Organization for Drug Control and Research (Égypte), avec 9 autres affiliations. Pays d’affiliation : Égypte.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.