Propyl gallate induces cell death in human pulmonary fibroblast through increasing reactive oxygen species levels and depleting glutathione.

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.

Propyl gallate induces human pulmonary fibroblast cell death through the regulation of Bax and caspase-3.

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.

Chemical analysis of n-propyl gallate used as pre-treatment for resin-dentin bond strength: In vitro study.

This study aimed to evaluate the effect of n-propyl gallate as pre-treatment for resin-dentin bond strength. The dentin pre-treatments evaluated included propyl gallate of concentrations 0.1% (w/v), 1.0% (w/v), and 10.0% (w/v), as well as glutaraldehyde 5.0% (v/v), and distilled water as a control treatment. Dentin specimens were prepared for Fourier Transformed Infrared Spectroscopy (FT-IR) (n = 3/pre-treatment). Pre-treatments were actively applied to dentin blocks before performing the adhesive procedure to composite resin. Microtensile bond strength to dentin (µTBS) (n = 8/pre-treatment) was determined after 24 h and 6 months of storage. Data were submitted to a two-way ANOVA, followed by Tukey's post hoc test. As for FT-IR, propyl gallate 1%-treated specimens presented higher water, carbonate, collagen, and amide absorbance rates compared to other tested groups, while specimens pre-treated with glutaraldehyde and distilled water presented similar absorbance curves. Regarding µTBS, all concentrations of propyl gallate resulted in statistically significant higher bond strength values than distilled water at 24 h. After 6 months of storage, propyl gallate 0.1% was the only group that maintained µTBS over time. Propyl gallate 0.1% might be a suitable dentinal pre-treatment due to being able to present chemical bonds with demineralized dentin and providing resin-dentin bond stability after 6 months of storage.

Aluminum induces lipid peroxidation and aggregation of human blood platelets

Aluminum (Al3+) intoxication is thought to play a major role in the development of Alzheimer's disease and in certain pathologic manifestations arising from long-term hemodialysis. Although the metal does not present redox capacity, it can stimulate tissue lipid peroxidation in animal models. Furthermore, in vitro studies have revealed that the fluoroaluminate complex induces diacyglycerol formation, 43-kDa protein phosphorylation and aggregation. Based on these observations, we postulated that Al3+-induced blood platelet aggregation was mediated by lipid peroxidation. Using chemiluminescence (CL) of luminol as an index of total lipid peroxidation capacity, we established a correlation between lipid peroxidation capacity and platelet aggregation. Al3+ (20-100 muM) stimulated CL production by human blood platelets as well as their aggregation. Incubation of the platelets with the antioxidants nor-dihydroguaiaretic acid (NDGA) (100 muM) and n-propyl gallate (NPG) (100 muM), inhibitors of the lipoxygenase pathway, completely prevented CL and platelet aggregation. Acetyl salicylic acid (ASA) (100 muM), an inhibitor of the cyclooxygenase pathway, was a weaker inhibitor of both events. These findings suggest that Al3+ stimulates lipid peroxidation and the lipoxygenase pathway in human blood platelets thereby causing their aggregation.