Effect of chemically modified natural porphyrins and copper and silver complexes derived from them on oxidative stress induced by paraquat and radiation

In the present work, chlorophyll a and deuteroporphyrin IX derivatives and copper (II) and silver (II) porphyrinates based on them were investigated for their ability to prevent oxidative stress in human HeLa cells exposed to paraquat (PQ) using fluorometric microculture cytotoxicity assay (FMCA). Among the compounds studied Ag-methylpyropheophorbide a and Cu-methylpyropheophorbide a contributed to a statistically significant increase in the survival of PQ-exposed cells. Additionally, ROS levels in HeLa cells were analyzed by flow cytometry using 2',7'-dichlorofluorescein diacetate and Ag-methylpyropheophorbide a and Cu-methylpyropheophorbide a were shown to arrest PQ-mediated oxidative stress. Furthermore, these two compounds were tested for radioprotective activity in the experiment with irradiation of HeLa cells at doses of 3 Gy and 6 Gy. According to the FMCA results, the addition of Ag-methylpyropheophorbide a and Cu-methylpyropheophorbide a to the cell culture had no increase in cell survival compared to the positive control, demonstrating the absence of radioprotective effect of these compounds. It can be assumed that the difference in the effects of these porphyrin derivatives on cell survival is related to different localization of oxidative stress targets in cells exposed to PQ or ionizing radiation.