Ticagrelor Attenuates Apoptosis of Lung and Myocardial Cells Induced by Abdominal Aorta Ischemia/Reperfusion.

Aim: 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.
Materials and 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.
Conclusion: 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.
(Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)