Ticagrelor Attenuates Apoptosis of Lung and Myocardial Cells Induced by Abdominal Aorta Ischemia/Reperfusion.
OBJECTIVE
This study aimed to analyze the effect of ticagrelor pretreatment on the prevention of lung and heart injury induced by abdominal aorta ischemia and reperfusion (I/R) and also to determine the effective dose.


METHODS
Thirty-five male Sprague-Dawley rats weighing 350-400 g were randomized into five groups. The animals received ticagrelor at doses of 7.5 mg/kg, 15 mg/kg and 25 mg/kg or normal saline 0.1 ml/kg orally via gastric gavage before the ischemic period. In the control and study groups, I/R injury was induced by clamping the aorta infrarenally for 2 hs, followed by 4 h of reperfusion. After sacrifice, hearts and lungs of the animals were extracted for both histopathological and biochemical analysis.


RESULTS
There was a significant difference between the animals that received 7.5 mg/kg and 25 mg/kg and 15 mg/kg and 25 mg/kg dose of ticagrelor regarding tissue malondealdehyde (MDA), and glutathione reductase levels in both lung and heart Ticagrelor treatment at 25 mg/kg led to significant cardiac remodeling activity and normal lung architecture against I/R induced injury. The number of TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells in alveolar epithelium and myocytes were increased in the sections from saline (I/R) group rats, and decreased following 25 mg/kg ticagrelor treatment.


CONCLUSIONS
Ticagrelor dose-dependently inhibits platelet aggregation, increases cyclooxygenase-2 and also inhibits cellular uptake of adenosine all resulting in attenuation of I/R injury. Ticagrelor at 25 mg/kg was determined as the dose effective against I/R-induced injury in lung and heart in Sprague-Dawley rats in the present study.
Department of Cardiovascular Surgery, Derince Education and Research Hospital, Kocaeli, Turkey.
Orhan
O
Findik
Department of Cardiovascular Surgery, Derince Education and Research Hospital, Kocaeli, Turkey.
Atike Tekeli
AT
Kunt
Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey.
Yusufhan
Y
Yazir
Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey.
Melda
M
Yardimoğlu
Department of Multidisciplinary Molecular Medicine, Institute of Health Sciences, Faculty of Medicine, Yeditepe University, Istanbul, Turkey.
Seda Güleç
SG
Yilmaz
Department of Cardiovascular Surgery, Bursa Education and Research Hospital, Bursa, Turkey.
Ufuk
U
Aydin
Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey.
Selenay Furat
SF
Rençber
Department of Cardiovascular Surgery, Derince Education and Research Hospital, Kocaeli, Turkey.
Ozgur
O
Baris
Department of Anesthesia and Reanimation, Derince Education and Research Hospital, Kocaeli, Turkey.
Canan
C
Balci
Deparment of Medical Biology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey tisbir@superonline.com.
Turgay
T
Isbir
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000503:physiopathology*; D017209:Apoptosis / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005980:Glutathione Reductase / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D000077486:Ticagrelor
D058921:Purinergic P2Y Receptor Antagonists; D008315:Malondialdehyde; D051546:Cyclooxygenase 2; D005980:Glutathione Reductase; D000077486:Ticagrelor; D000241:Adenosine
Ticagrelor; heart; ischemia and reperfusion; lung