Drug Design, Development and Therapy (Nov 2019)

Postconditioning Protection Against Myocardiocyte Anoxia/Reoxygenation Injury From Penehyclidine Hydrochloride

  • Ren JY,
  • Lin DM,
  • Wang CB,
  • Yang YL,
  • Wang ZQ,
  • Cui BQ,
  • Ma J

Journal volume & issue
Vol. Volume 13
pp. 3977 – 3988

Abstract

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JY Ren,* DM Lin,* CB Wang, YL Yang, ZQ Wang, BQ Cui, J Ma Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: J MaDepartment of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, No.2 Anzhen Road, Chaoyang District, Beijing 100029, People’s Republic of ChinaTel +8613370103571Email [email protected]/Aims: To investigate the postconditioning protective effect of penehyclidine hydrochloride (PHC) against anoxia/reoxygenation (A/R) injury in H9c2 cells along with the involved mechanism and timing effect.Methods: We divided H9c2 cells into 7 groups: control group, A/R group and PHC+A/R groups at 0 min, 5 mins, 10 mins, 20 mins, 30 mins, respectively (treated with 0.1 μm/L PHC at 0 min, 5 mins, 10 mins, 20 mins, 30 mins after the reoxygenation procedure began). Cell apoptosis, oxidative stress, intracellular Ca2+ concentration, mitochondrial membrane potential and mitochondrial permeability transition pore (MPTP) opening were explored. Bcl-2, Bax, Cyt C, caspase-3 and caspase-9 levels were measured.Results: A/R significantly increased both cell injury and cell apoptosis. PHC showed postconditioning protective effect by attenuating superoxide production, decreasing Ca2+ overload, restraining MPTP activities, restoring mitochondrial membrane potential, regulating cell apoptosis proteins and modulation of mitochondrial pathway. Earlier administration of PHC offered greater postconditioning protective effect.Conclusion: H9c2 cells were protected by PHC from A/R injury regardless of timing of PHC administration (0 min, 5 mins, 10 mins, 20 mins, 30 mins). However, earlier administration of PHC resulted in better PHC postconditioning protection.Keywords: penehyclidine hydrochloride, PHC, anoxia/reoxygenation injury, A/R injury, cell apoptosis, oxidative stress, mitochondrial pathway

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