The Effects And Mechanisms Of Pentoxifylline On Tumor Necrosis Factor Alpha-induced Apoptosis In Neonatal Rat Cardiocytes

Objective It had been clinically demonstrated that pentoxifylline decreased TNF-αexpression and contributed to the improvement in the patients with chronic heart failure. However, the mechanisms of pentoxifylline in TNF-α-mediated myocardial apoptosis were not fully understood. This study was to investigate the effect of pentoxifylline (PTX) on apoptosis induced by TNF-αand its regulation mechanism in neonatal rat cadiocytes.Methods Neonatal rat cadiocytes were cultured in vitro and divided into four groups : control group, 100μg/ml PTX, 300μg/ml PTX , 500μg/ml PTX. Terminal deoxynuc leotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and Flow cytometry methods were employed to observe occurrence of apoptosis, and semi-quantitative reverse-transcriptase polymerase chain reactions were used to determine the gene expressions of iNOS, AKT and NF-κB.Results With the increase of PTX, the occurrence of apoptosis with Flow cytometry significantly reduced from (25.82±1.98) % to (20.78±1.29) %, ( 15.73±1.29) %, (10.03±2.13) %, with TUNEL from (25.55±0.88) % to ( 19.35±1.13) %, ( 15.00±1.13) %, ( 10.20±1.58) %, respectively (p<0.01). Similarly, compared to the control group, nuclear factor kappaB(NF-κB)mRNA and AKT mRNA expressions in each PTX group were highly reduced and their expressions were positively correlated to the concentration of PTX. Reversely, compared to the control group, iNOS mRNA expression in each PTX group had no significantly altered (p>0.05). Conclusions Our results showed that pentoxifyline, in a dose-dependence, was able to protected neonatal rat cadiocytes against TNF-α-induced apoptosis via inhibiting AKT and NF-κB mRNA expression in neonatal rat cardiomyocytes. Our study suggested that pentoxifylline was a novel pharmacological intervention in heart failure.