{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T16:05:23Z","timestamp":1779725123896,"version":"3.53.1"},"reference-count":21,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Sevoflurane, a widely used volatile anesthetic, can induce oxidative stress and apoptosis, but the underlying mechanisms in human cardiomyocytes remain unclear. This study investigated the role of transient receptor potential vanilloid 1 (TRPV1) channels in sevoflurane-induced cardiotoxicity and the potential mitigating effect of ascorbic acid. Materials and Methods: Human cardiomyocytes were exposed to sevoflurane (5.1%, 6 h) and\/or ascorbic acid (1 mM, 30 min), with or without the TRPV1 channel antagonist capsazepine and with the TRPV1 channel agonist Capsaicin. Intracellular calcium, reactive oxygen species (ROS), apoptosis, mitochondrial membrane potential, and caspase-3\/9 activities were assessed. Results: Sevoflurane significantly increased intracellular calcium levels, ROS production, mitochondrial depolarization, apoptosis, and caspase-3\/9 activity compared with controls (p &lt; 0.001). These effects were attenuated by capsazepine, suggesting a role for TRPV1 involvement. Ascorbic acid pretreatment significantly reduced sevoflurane-induced elevations in all parameters (p &lt; 0.001). Combined ascorbic acid and capsazepine treatment yielded further reductions in calcium, ROS, apoptosis, and caspase activities compared to ascorbic acid alone (p &lt; 0.05). Conclusions: Sevoflurane induces apoptosis in human cardiomyocytes via ROS-mediated activation of the TRPV1 channel, leading to calcium overload, mitochondrial dysfunction, and caspase-dependent cell death. Ascorbic acid exerts mitigating effects by reducing oxidative stress and modulating TRPV1 channel activity, suggesting a potential therapeutic strategy for myocardial protection during sevoflurane anesthesia.<\/jats:p>","DOI":"10.3390\/medicina62050945","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T15:05:08Z","timestamp":1779721508000},"page":"945","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of Sevoflurane-Induced Apoptotic Damage in Human Cardiomyocytes and the Protective Efficacy of Ascorbic Acid"],"prefix":"10.3390","volume":"62","author":[{"given":"Ey\u00fcp","family":"Aydo\u011fan","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Reanimation, Faculty of Medicine, Alanya Alaaddin Keykubat University, 07425 Alanya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130shak Suat","family":"\u00d6vey","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Alanya Alaaddin Keykubat University, 07425 Alanya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O\u011fuz","family":"Karahan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Faculty of Medicine, Alanya Alaaddin Keykubat University, 07425 Alanya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1007\/s00540-017-2375-6","article-title":"A clinical review of inhalation anesthesia with sevoflurane: From early research to emerging topics","volume":"31","author":"Brioni","year":"2017","journal-title":"J. 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