Sepsis is a pathophysiological event involving systemic inflammatory response syndrome, multiple organ failure syndromes, and tissue damage. Overproduction of free radicals as a result of tissue damage during sepsis contributes to cellular toxicity, organ failure, and even mortality. Antioxidants, which scavenge free radicals, play a protective role against various diseases. Previous studies have shown that umbelliferone (UF) has antioxidant and anti-inflammatory effects. Since oxidative stress is naturally associated with sepsis-induced organ dysfunction, the application of antioxidant compounds could potentially illuminate the pathophysiology of sepsis, which does not yet have an effective treatment. The sepsis model induced by cecal ligation and puncture (CLP) was applied to rats. Different doses of UF (10░mg/kg, 20░mg/kg, and 40░mg/kg) on oxidant-antioxidant in septic rats, mRNA of inflammatory mediators such as tumor necrosis factor- α (TNF-α) and interleukin (IL)-1 its effects on expression levels were evaluated in lung, kidney, and liver tissues. When the lung, kidney, and liver tissues of septic rats were compared with those of the control group, it was found that UF administration increased dose-dependent superoxide dismutase activity and glutathione levels and significantly decreased malondialdehyde levels. The effects of UF administration on oxidative parameters were dose-dependent. The 40░mg/kg UF dose showed greater anti-oxidative properties than the 20░mg/kg and 10░mg/kg doses for all the evaluated parameters. Further, the TNF- α mRNA expression of the CLP +40░mg/kg group was reduced to a level comparable to that of the control group. UF has been found to be an effective molecule in reducing oxidative stress by supporting endogenous antioxidants and enhancing the scavenging effects of free radicals. The potent antioxidant property of UF may also be related to the suppression of the cytokine cascade during sepsis. The results suggest that UF administration may represent a new treatment for the prevention of lung, kidney and liver damage caused by septic conditions.

Objective: The aim of this study was to explore the role of endothelin 1 (ET-1) in human breast cancer proliferation and migration and antagonism of endothelin receptor A (ETAR) and endothelin receptor B (ETBR) by using the non-selective dual ETA/ETB receptor antagonist bosentan and determine its anti-proliferative, anti-metastatic, and apoptotic effects demonstrated by nuclear factor kappa B (NF-kB), vascular endothelial growth factor (VEGF), Caspase 3 and Caspase 9 expression on endothelin-induced proliferation of MCF-7 cell line in vitro. Materials and Methods: A total of 8,000 cells were seeded into e-plates 24 hours after the cells were incubated with or without 10-4 M BOS (1 hour before ET-1 treatment); 10-7, 10-8, and 10-9 M ET-1 for 1-4 days. Results: Whether ET-1 is present or not in the tumor area, bosentan exerts anti-proliferative effect on breast cancer. However, ET-1 and bosentan group showed important inhibitory effect on tumor migration compared to bosentan alone, which can be attributed to increased activity of ET-1 axis in the presence of ET-1. The imbalance among the NF-kB, caspases, and VEGF, which are predictive factors of carcinogenesis significantly improved after bosentan administration. Conclusion: Our study definitely demonstrated ET-1 and its critical role in cancer progression with apoptotic and anti-apoptotic pathways (NF-κB) and VEGF expression, and migration analyses were also performed. The second major finding was that bosentan inhibited ET-1-mediated effects on tumor proliferation and migration. Cite this article as: Cinar I, Yayla M, Celik M, Bilen A, Bayraktutan Z. Role of Endothelin 1 on Proliferation and Migration of Human MCF-7 Cells. Eurasian J Med 2020; 52(3): 277-82.

Objective: The aim of the study is to investigate the protective effects of nicotinamide riboside on oxidative stress in an experimental sepsis model created by cecal ligation and puncture. Materials and Methods: Rats were divided into 3 groups randomly: sham-operated (control) group, sep- sis group, and nicotinamide riboside-treated group. Sepsis model-induced cecal ligation and puncture was applied to sepsis group rats. Animals in the nicotinamide riboside-treated group were administered nicotin- amide riboside intraperitoneally (500 mg/kg). Tissue specimens from rats were biochemically calculated for their activities of catalase, superoxide dismutase, glutathione peroxidase, myeloperoxidase, and malondialde- hyde levels. Ovarian tissues of all rats were histopathologically evaluated. Results: Catalase, superoxide dismutase, and glutathione peroxidase activities were lower in the sepsis group compared to the sham-operated (control) group. Superoxide dismutase activity was significantly higher in the nicotinamide riboside-treated group than in control and sepsis group (P < .05). Myeloperoxidase activi- ties and mean malondialdehyde concentration of ovarian tissue were lower in nicotinamide riboside-treated group than in sepsis group (P < .05). The light microscopic assessment revealed that ovarian tissue was protected, and inflammation and interstitial edema decreased in nicotinamide riboside-treated group. The follicular damage findings were notably decreased in nicotinamide riboside-treated group in comparison to sepsis group (P<0.05). Conclusion: Our findings indicated that nicotinamide riboside diminished ovarian injury in sepsis via inhibiting tissue infiltration and increasing endogenous antioxidant capacity. Nicotinamide riboside administration may represent a new treatment approach for the prevention of sepsis-induced ovarian injury. Cite this article as: Selli J, Vural Keles D, Nuri Keles ON, Celik M, Yetim Z. Nicotinamide riboside preserves ovarian injury in an experimental sepsis model in rats. Eurasian J Med. 2023;55(2), 128-134.