RESUMEN
Propyl gallate (PG) exhibits an anti-growth effect on various cell types. The present study investigated the impact of PG on the levels of reactive oxygen species (ROS) and glutathione (GSH) in primary human pulmonary fibroblast (HPF) cells. Moreover, the effects of N-acetyl cysteine (NAC, an antioxidant), L-buthionine sulfoximine (BSO, a GSH synthesis inhibitor), and small interfering RNA (siRNAs) against various antioxidant genes on ROS and GSH levels and cell death were examined in PG-treated HPF cells. PG (100-800 µM) increased the levels of total ROS and O2·- at early time points of 30-180 min and 24 h, whereas PG (800-1600 µM) increased GSH-depleted cell number at 24 h and reduced GSH levels at 30-180 min. PG downregulated the activity of superoxide dismutase (SOD) and upregulated the activity of catalase in HPF cells. Treatment with 800 µM PG increased the number of apoptotic cells and cells that lost mitochondrial membrane potential (MMP; ΔΨm). NAC treatment attenuated HPF cell death and MMP (ΔΨm) loss induced by PG, accompanied by a decrease in GSH depletion, whereas BSO exacerbated the cell death and MMP (ΔΨm) loss without altering ROS and GSH depletion levels. Furthermore, siRNA against SOD1, SOD2, or catalase attenuated cell death in PG-treated HPF cells, whereas siRNA against GSH peroxidase enhanced cell death. In conclusion, PG induced cell death in HPF cells by increasing ROS levels and depleting GSH. NAC was found to decrease HPF cell death induced by PG, while BSO enhanced cell death. The findings shed light on how manipulating the antioxidant system influence the cytotoxic effects of PG in HPF cells.
Asunto(s)
Chrysanthemum , Galato de Propilo , Humanos , Galato de Propilo/farmacología , Antioxidantes/farmacología , Especies Reactivas de Oxígeno , Catalasa , Muerte Celular , Fibroblastos , Glutatión , Butionina Sulfoximina/farmacología , ARN Interferente Pequeño/genéticaRESUMEN
Propyl gallate (PG) has been found to exert an inhibitory effect on the growth of different cell types, including lung cancer cells. However, little is known about the cytotoxicological effects of PG specifically on normal primary lung cells. The current study examined the cellular effects and cell death resulting from PG treatment in human pulmonary fibroblast (HPF) cells. DNA flow cytometry results demonstrated that PG (100-1,600 µM) had a significant impact on the cell cycle, leading to G1 phase arrest. Notably, 1,600 µM PG slightly increased the number of sub-G1 cells. Additionally, PG (400-1,600 µM) resulted in the initiation of cell death, a process that coincided with a loss of mitochondrial membrane potential (MMP; ΔΨm). This loss of MMP (ΔΨm) was evaluated using a FACS cytometer. In PG-treated HPF cells, inhibitors targeting pan-caspase, caspase-3, caspase-8, and caspase-9 showed no significant impact on the quantity of annexin V-positive and MMP (ΔΨm) loss cells. The administration of siRNA targeting Bax or caspase-3 demonstrated a significant attenuation of PG-induced cell death in HPF cells. However, the use of siRNAs targeting p53, Bcl-2, or caspase-8 did not exhibit any notable effect on cell death. Furthermore, none of the tested MAPK inhibitors, including MEK, c-Jun N-terminal kinase (JNK), and p38, showed any impact on PG-induced cell death or the loss of MMP (ΔΨm) in HPF cells. In conclusion, PG induces G1 phase arrest of the cell cycle and cell death in HPF cells through apoptosis and/or necrosis. The observed HPF cell death is mediated by the modulation of Bax and caspase-3. These findings offer insights into the cytotoxic and molecular effects of PG on normal HPF cells.
Asunto(s)
Glutatión , Galato de Propilo , Humanos , Galato de Propilo/metabolismo , Galato de Propilo/farmacología , Caspasa 8/metabolismo , Caspasa 8/farmacología , Proteína X Asociada a bcl-2/metabolismo , Proteína X Asociada a bcl-2/farmacología , Caspasa 3/metabolismo , Caspasa 3/farmacología , Glutatión/metabolismo , Glutatión/farmacología , Especies Reactivas de Oxígeno/metabolismo , Proliferación Celular , Muerte Celular , Apoptosis , Pulmón , Fibroblastos/metabolismoRESUMEN
Background The clinical significance of complete revascularization for ST segment elevation myocardial infarction (STEMI) pa-tients during admission is still debatable. Methods A total of 1406 STEMI patients from the Korean Myocardial Infarction Registry with multivessel diseases without cardiogenic shock who underwent primary percutaneous coronary intervention (PPCI) were analyzed. We used propensity score matching (PSM) to control differences of baseline characteristics between culprit only intervention (CP) and multivessel percutaneous coronary interventions (MP), and between double vessel disease (DVD) and triple vessel disease (TVD). The major adverse cardiac event (MACE) was analyzed for one year after discharge. Results TVD patients showed higher incidence of MACE (14.2%vs. 8.6%, P=0.01), any cause of revascularization (10.6%vs. 5.9%, P=0.01), and repeated PCI (9.5%vs. 5.7%, P=0.02), as compared to DVD patients during one year after discharge. MP reduced MACE effectively (7.3%vs. 13.8%, P=0.03), as compared to CP for one year, but all cause of death (1.6%vs. 3.2%, P=0.38), MI (0.4%vs. 0.8%, P=1.00), and any cause of revascularization (5.3%vs. 9.7%, P=0.09) were comparable in the two treatment groups. Conclusions STEMI patients with TVD showed higher rate of MACE, as compared to DVD. MP performed during PPCI or ad hoc during admission for STEMI patients without cardiogenic shock showed lower rate of MACE in this large scaled database. Therefore, MP could be considered as an effective treatment option for STEMI patients without cardiogenic shock.