Hydroperoxy-eicosatetraenoyl-phosphatidylethanolamine (HpETE-PE) is a ferroptotic cell death signal. HpETE-PE is produced by the 15-Lipoxygenase (15LOX)/Phosphatidylethanolamine Binding Protein-1 (PEBP1) complex or via an Fe-catalyzed non-enzymatic radical reaction. Ferrostatin-1 (Fer-1), a common ferroptosis inhibitor, is a lipophilic radical scavenger but a poor 15LOX inhibitor arguing against 15LOX having a role in ferroptosis. In the current work, we demonstrate that Fer-1 does not affect 15LOX alone, however, it effectively inhibits HpETE-PE production by the 15LOX/PEBP1 complex. Computational molecular modeling shows that Fer-1 binds to the 15LOX/PEBP1 complex at three sites and could disrupt the catalytically required allosteric motions of the 15LOX/PEBP1 complex. Using nine ferroptosis cell/tissue models, we show that HpETE-PE is produced by the 15LOX/PEBP1 complex and resolve the long-existing Fer-1 anti-ferroptotic paradox.

Objective: In this study, we aimed to evaluate the relationship between thiol-disulfide homoeostasis and hemogram parameters in COVID-19 patients. Methods: Total thiol(TT), Native thiol(NT), dynamic disulfide status(DDS), DDS/NT, DDS/TT, NT/TT ratio and CBC parameters were analyzed in 68 patients with positive COVID-19 and 31 healthy individuals. Results: TT, NT, DD, hemoglobin and hematocrit levels were higher in the control group than in patient groups. TT, NT, DD and lymphocyte levels of COVID-19 patients treated in medical floor were higher than those treated in intensive care unit; WBC, neutrophil and NLR were low(P<0.05).PLR was higher in intensive care patients compared with the control group(P<0.05).COVID-19 patients who did not need mechanical ventilation were retrospectively evaluated according to their mortality. TT, NT, DDS and lymphocyte levels were higher; WBC, Neutrophil, PLR and NLR were lower(P<0.05) in survivors. The diagnostic performance of TT, NT and DDS levels to define requirement of intensive care treatment in COVID-19 patients were evaluated by using Receiver Operating Characteristic (ROC) curve analysis. By using ROC analysis, the optimum cut-off points for of TT, NT and DDS levels showed high sensitivity and specificity for requirement of intensive care treatment(P<0.05). Conclusions: According to our results, it has been observed that the thiol-disulfide balance is disrupted In COVID-19 patients. It may be beneficial to monitor the thiol-disulfide balance in the follow-up and treatment of the patients. Amaç: Bu çalışmada, COVID-19 hastalarında tiyol-disülfid homoeostazı ile hemogram parametreleri arasındaki ilişkiyi değerlendirmeyi amaçladık. Gereç Yöntem: Total tiyol (TT), Native tiyol (NT), dinamik disülfid durumu (DDS), DDS / NT, DDS / TT, NT / TT oranı ve CBC parametreleri COVID-19 pozitif 68 hasta ve 31 sağlıklı bireyde analiz edildi. Bulgular: Kontrol grubunda TT, NT, DD, hemoglobin ve hematokrit düzeyleri hasta gruplarına göre daha yüksekti. Serviste tedavi gören COVID-19 hastalarının TT, NT, DD ve lenfosit seviyeleri yoğun bakım ünitesinde tedavi edilenlere göre daha yüksekti; WBC, nötrofil ve NLO düşüktü (P <0.05). Yoğun bakım hastalarında PLR, kontrol grubuna göre daha yüksekti (P <0.05). Mekanik ventilasyona ihtiyaç duymayan COVID-19 hastaları mortalitelerine göre geriye dönük olarak değerlendirildi. TT, NT, DDS ve lenfosit seviyeleri daha yüksekti; Hayatta kalanlarda WBC, Nötrofil, PLR ve NLR daha düşüktü (P <0.05). COVID-19 hastalarında yoğun bakım tedavisi gereksinimini tanımlamak için TT, NT ve DDS düzeylerinin tanısal performansı, ROC eğrisi analizi kullanılarak değerlendirildi. ROC analizine göre, yoğun bakım tedavisi gereksinimi için TT, NT ve DDS düzeyleri optimum kestirim değerlerinde, yüksek duyarlılık ve özgüllük göstermiştir (P <0.05). Sonuç: Sonuçlarımıza göre COVID-19 hastalarında tiyol-disülfid dengesinin bozulduğu görüldü. Hastaların takip ve tedavisinde tiyol-disülfid dengesinin izlenmesi faydalı olabilir.