Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin
Corresponding Author
Seyhan Ayik
Department of Medical Pharmacology, Inonu University, Malatya, Turkey
Correspondence
Seyhan Ayik, Department of Medical Pharmacology, Inonu University, Malatya 44280, Turkey.
Email: [email protected]
Search for more papers by this authorMehmet Gunata
Department of Medical Pharmacology, Inonu University, Malatya, Turkey
Search for more papers by this authorOnural Ozhan
Department of Medical Pharmacology, Inonu University, Malatya, Turkey
Search for more papers by this authorAzibe Yildiz
Department of Histology and Embryology, Inonu University, Malatya, Turkey
Search for more papers by this authorNigar Vardi
Department of Histology and Embryology, Inonu University, Malatya, Turkey
Search for more papers by this authorEmre Sonmez
Department of Cardiology, Inonu University, Malatya, Turkey
Search for more papers by this authorNecip Ermis
Department of Cardiology, Inonu University, Malatya, Turkey
Search for more papers by this authorNilay Ates
Department of Medical Pharmacology, Istanbul Medipol University, Istanbul, Turkey
Search for more papers by this authorErtugrul Kilic
Department of Physiology, Istanbul Medipol University, Istanbul, Turkey
Search for more papers by this authorSamir Abbas Ali Noma
Biochemistry and Biomaterials Research Laboratory, Department of Chemistry, Inonu University, Malatya, Turkey
Search for more papers by this authorAhmet Ulu
Biochemistry and Biomaterials Research Laboratory, Department of Chemistry, Inonu University, Malatya, Turkey
Search for more papers by this authorSeyfullah Taha Inan
Department of Medical Pharmacology, Inonu University, Malatya, Turkey
Search for more papers by this authorHaci Ahmet Acet
Department of Medical Pharmacology, Inonu University, Malatya, Turkey
Search for more papers by this authorHakan Parlakpinar
Department of Medical Pharmacology, Inonu University, Malatya, Turkey
Search for more papers by this authorCorresponding Author
Seyhan Ayik
Department of Medical Pharmacology, Inonu University, Malatya, Turkey
Correspondence
Seyhan Ayik, Department of Medical Pharmacology, Inonu University, Malatya 44280, Turkey.
Email: [email protected]
Search for more papers by this authorMehmet Gunata
Department of Medical Pharmacology, Inonu University, Malatya, Turkey
Search for more papers by this authorOnural Ozhan
Department of Medical Pharmacology, Inonu University, Malatya, Turkey
Search for more papers by this authorAzibe Yildiz
Department of Histology and Embryology, Inonu University, Malatya, Turkey
Search for more papers by this authorNigar Vardi
Department of Histology and Embryology, Inonu University, Malatya, Turkey
Search for more papers by this authorEmre Sonmez
Department of Cardiology, Inonu University, Malatya, Turkey
Search for more papers by this authorNecip Ermis
Department of Cardiology, Inonu University, Malatya, Turkey
Search for more papers by this authorNilay Ates
Department of Medical Pharmacology, Istanbul Medipol University, Istanbul, Turkey
Search for more papers by this authorErtugrul Kilic
Department of Physiology, Istanbul Medipol University, Istanbul, Turkey
Search for more papers by this authorSamir Abbas Ali Noma
Biochemistry and Biomaterials Research Laboratory, Department of Chemistry, Inonu University, Malatya, Turkey
Search for more papers by this authorAhmet Ulu
Biochemistry and Biomaterials Research Laboratory, Department of Chemistry, Inonu University, Malatya, Turkey
Search for more papers by this authorSeyfullah Taha Inan
Department of Medical Pharmacology, Inonu University, Malatya, Turkey
Search for more papers by this authorHaci Ahmet Acet
Department of Medical Pharmacology, Inonu University, Malatya, Turkey
Search for more papers by this authorHakan Parlakpinar
Department of Medical Pharmacology, Inonu University, Malatya, Turkey
Search for more papers by this authorAbstract
Background
Despite the available treatments, pulmonary arterial hypertension (PAH) prognosis is poor.
Objectives
We aimed to investigate the effects of the alamandine (ALA), melatonin (MEL), and ALA + MEL in PAH.
Methods
The 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 μg/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.
Results
Monotherapies, 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 α-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 α-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.
Conclusion
ALA, 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.
CONFLICT OF INTEREST STATEMENT
The authors declared no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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