Abstract
Pentoxifylline (PTX) is a methylxanthine derivative that has been developed as an immunomodulatory agent and an improvement of microcirculation. Osteoradionecrosis (ORN) is a serious complication of radiation therapy due to hypovascularity. Coronavirus disease 2019 (COVID-19) has spread globally. Symptoms for this disease include self-limiting respiratory tract illness to severe pneumonia and acute respiratory distress. In this study, the effects of PTX on RAW 264.7 cells were investigated to reveal the possibility of PTX as a therapeutic agent for ORN and COVID-19. To reveal PTX effects at the cellular level, protein expression profiles were analyzed in the PTX-treated RAW 264.7 cells by using immunoprecipitation high-performance liquid chromatography (IP-HPLC). PTX-treated RAW 264.7 cells showed increases in immunity- and osteogenesis-related proteins and concurrent decreases in proliferation-, matrix inflammation-, and cellular apoptosis-related proteins expressions. The IP-HPLC results indicate that PTX plays immunomodulatory roles in RAW 264.7 cells by regulating anti-inflammation-, proliferation-, immunity-, apoptosis-, and osteogenesis-related proteins. These results suggest that PTX may be used as supplement medications for ORN as well as for COVID-19.
Highlights
Pentoxifylline (PTX) is a methylxanthine derivative (1-(5-oxohexyl)-3,7-dimethylxanthine) that has been used for the past several decades to improve the blood rheological properties and treat symptoms associated with impaired microcirculation [1]
Changes of proliferating cell nuclear antigen (PCNA), PLK4, p14, and p16 were measured within ±5% in response to PTX, which were analogous with control housekeeping proteins (Figure 1a)
In spite of there being a direct characterization between major inflammatory diseases such as COVID-19 and different protein expression profiles of unstimulated murine RAW 264.7 cells, we have tried to reveal and clarify the basic characteristics of PTX profiling
Summary
Pentoxifylline (PTX) is a methylxanthine derivative (1-(5-oxohexyl)-3,7-dimethylxanthine) that has been used for the past several decades to improve the blood rheological properties and treat symptoms associated with impaired microcirculation [1]. Other methylated xanthine compounds, which include caffeine, theophylline, aminophylline, and theobromine, are plant components and have similar major pharmacologic actions [2]. The major enzymatic action of cyclic nucleotide phosphodiesterases (PDEs) is the degradation of cyclic adenosine monophosphate (cAMP). PTX works as a nonselective inhibitor of PDEs, and upregulates the effects of cAMP and adenosine-50 -triphosphate and increases erythrocyte distensibility. PTX reduces leukocyte adhesion to endothelial cells, enhances prostacyclin synthesis, and diminishes platelets aggregation. The accumulation of the above effects leads to capillary dilatation, a reduction in blood viscosity, and an improvement in peripheral microvasculature [3]
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