Postconditioning Protection Against Myocardiocyte Anoxia/Reoxygenation Injury From Penehyclidine Hydrochloride

• Published in: Drug design, development and therapy development and therapy, 2019-11, Vol.13, p.3977-3988
• Main Authors: Ren, J Y, Lin, D M, Wang, C B, Yang, Y L, Wang, Z Q, Cui, B Q, Ma, J
• Format: Article
• Language: English
• Subjects: Anoxia; anoxia/reoxygenation (a/r) injury; Apoptosis; Apoptosis - drug effects; Bax protein; Bcl-2 protein; Calcium (intracellular); Calcium (mitochondrial); Calcium ions; Calcium permeability; Cardiovascular disease; Caspase-3; Caspase-9; cell apoptosis; Cell injury; Cell Line; Cytochrome c; Experiments; Flow cytometry; Humans; Hypoxia - drug therapy; Hypoxia - metabolism; Hypoxia - pathology; Injuries; Ischemia; Membrane permeability; Membrane potential; Membranes; Mitochondria; mitochondrial pathway; Mitochondrial permeability transition pore; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Original Research; Oxidative stress; penehyclidine hydrochloride (phc); Permeability; Pharmacology; Protective Agents - administration & dosage; Protective Agents - pharmacology; Proteins; Quinuclidines - administration & dosage; Quinuclidines - pharmacology; Stress concentration; Superoxide; Superoxides
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S224282

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. 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 Ca 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. A/R significantly increased both cell injury and cell apoptosis. PHC showed postconditioning protective effect by attenuating superoxide production, decreasing Ca 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. 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.