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    Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin
    (Wiley, 2024) Ayik, Seyhan; Gunata, Mehmet; Ozhan, Onural; Yildiz, Azibe; Vardi, Nigar; Sonmez, Emre; Ermis, Necip
    BackgroundDespite the available treatments, pulmonary arterial hypertension (PAH) prognosis is poor.ObjectivesWe aimed to investigate the effects of the alamandine (ALA), melatonin (MEL), and ALA + MEL in PAH.MethodsThe rats were randomly divided into Control (n = 10), monocrotaline (MCT) (n = 12), ALA (n = 12), MEL (n = 12), and ALA + MEL (n = 12) groups. PAH was induced by MCT. The ALA, MEL, and ALA + MEL groups received 50 mu g/kg/day ALA, 10 mg/kg/day MEL, and ALA + MEL, respectively, for 35 days. Echocardiographic and hemodynamic measurements and tissue analyses (morphometric, histopathological, ELISA, and western blot) were performed.ResultsMonotherapies, especially MEL, reduced the right ventricular (RV) systolic pressure. Only MEL increased the pulmonary artery acceleration time. MCT increased the RV/left ventricle (LV) + interventricular septum (IVS) ratio. While ALA and ALA + MEL slightly decreased the RV/(LV + IVS), MEL significantly restored it. MCT increased the tunica intima-media (TIM) thickness, PCNA and alpha-SMA of pulmonary arterioles, histopathological score (HS) (inflammatory infiltration etc.) of the lung, and RV. All treatments reduced the TIM thickness (especially MEL), PCNA, and alpha-SMA. All treatments significantly decreased the HS of the lung; however, MEL and ALA + MEL produced greater benefits. All treatments attenuated the HS of RV. MCT caused a significant increase in lung lysyl oxidase (LOX) activity. All treatments restored the LOX; however, MEL and ALA + MEL provided greater improvement. While lung Nrf-2 was increased in MCT-treated rats, MEL reduced it.ConclusionALA, MEL, and ALA + MEL attenuate PAH and protect RV via antiproliferative, anti-remodeling, antihypertrophic, anti-inflammatory, and free radical scavenging (only MEL) capabilities. Overall, MEL produced the best outcomes.
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    Cardiovascular impact of consumption of sulfured-dried Malatya apricots (Prunus armeniaca L.) at varying SO2 levels: A comprehensive assessment in a rat model
    (Pergamon-Elsevier Science Ltd, 2025) Ayik, Seyhan; Yildiz, Azibe; Ozhan, Onural; Karaca, Yucel; Taslidere, Elif; Ermis, Necip; Vardi, Nigar
    Apricots known as sulfured-dried are those dried under the sun with sulfur dioxide (SO2), which extends their shelf life. Although sun-dried apricots are renowned for their cardiovascular benefits, the cardiovascular effects of sulfured-dried apricots (SDAs) remain poorly understood. To address this knowledge gap, we designed the present study to investigate the cardiovascular effects of consuming SDAs at varying SO2 levels in a rat model. The rats were randomly assigned to 6 groups. The Control group received standard rat chow, while the other 5 groups were fed a diet containing 10 % SDAs with differing SO2 concentrations (1500 ppm, 2000 ppm, 2500 ppm, 3000 ppm, and 3500 ppm) for 24 weeks. After echocardiography and hemodynamic assessment, cardiac histopathology and serum biochemistry were evaluated. Our findings indicate that an SDA diet containing 3500 ppm SO2 leads to myocardial damage and subsequent cardiac dysfunction, likely through TNF-alpha-mediated inflammation and apoptosis. In contrast, diets containing SDAs with SO2 levels between 1500 and 2500 ppm appeared to pose minimal cardiovascular risk. Because in these groups, there was no evidence of myocardial damage, cardiac inflammation, apoptotic cell death, or cellular stress in the cardiac myocytes. Also, these groups showed normal cardiac function in echocardiographic assessments. These results suggest that consuming SDAs with SO2 concentrations up to 2500 ppm SO2 may be safe for cardiovascular health.