Influence of different radioprotective compounds on radiotolerance and cell cycle distribution of human progenitor cells of granulocytopoiesis <i>in vitro</i>

In this study, two chiral nitronyl nitroxyl radicals, L1 and D1, were synthesized and evaluated for their potential radioprotective properties invitro and invivo. We synthesized the new stable nitronyl nitroxide radicals, L1 and D1, according to Ullman’s method, and their chemical structures were characterized using UV-vis absorption, electron spin resonance (ESR), and circular dichroism (CD) spectra. The cytotoxicity of L1 and D1 on C6 glioma cells (C6 cells) was examined using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. To study the anti-radiation effects of L1 and D1 on C6 cells, we determined the optical density (OD) values of irradiated C6 cells using the MTT assay. The effects of L1 and D1 on the survival rate of mice after radiation exposure was evaluated. To demonstrate the influence of L1 and D1 pre-treatment on the antioxidant enzyme system, we studied the activities of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GSH) in mouse plasma after exposure to 6.5 Gy gamma radiation. The results showed that L1 and D1 did not have any obvious cytotoxicity at concentrations below 125μgmL−1. Moreover, L1 and D1 had the same cytotoxic effects on C6 cells. L1 and D1 significantly enhanced C6 cell survival after 8, 10, and 12 Gy radiation exposure, and there was no significant difference in the OD values between L1 and D1. The effects of these drugs on mouse survival rates were dose-dependent. Pre-treatment with different concentrations of L1, D1, or WR2721 significantly increased the activity of SOD, CAT, and GSH and significantly decreased the activity of MDA compared with radiation exposure only. In addition, the activities of SOD, CAT, and GSH in the L1 group were higher than those in the D1 group, whereas the activity of MDA was lower. Therefore, L1 and D1 have potential as safe and efficient therapeutic drugs against radiation damage.

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Synthesis and Characterization of Two Chiral Pyrrolyl α-Nitronyl Nitroxide Radicals and Determination of their Cytotoxicity and Radioprotective Properties in C6 Cells and Mice under Ionizing Radiation

Tian

Lan

Gao

et al. 2019

Aust. J. Chem.

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Therapeutic and Clinical Applications of Nitroxide Compounds

Soule

Hyodo

Matsumoto

et al. 2007

Antioxidants & Redox Signaling

115

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Nitroxide compounds have been used for many years as biophysical tools, but only during the past 15-20 years have the many interesting biochemical interactions been discovered and harnessed for therapeutic applications. By modifying oxidative stress and altering the redox status of tissues, nitroxides have the ability to interact with and alter many metabolic processes. This interaction can be exploited for therapeutic and research use, including protection against ionizing radiation, as probes in functional magnetic resonance imaging, cancer prevention and treatment, control of hypertension and weight, and protection from damage resulting from ischemia/reperfusion injury. Although much remains to be done, many applications have been well studied, and some are presently being tested in clinical trials. The therapeutic and research uses of nitroxides are reviewed here, with a focus on the progress from initial development to modern, state-of-the art trials.

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Protection Against Radiation Induced Hematopoietic Damage in Bone Marrow of Swiss Albino Mice by Mentha piperita (Linn)

Samarth

2007

JRR

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The protective effects of Mentha piperita (Linn) extract against radiation induced hematopoietic damage in bone marrow of Swiss albino mice have been studied. Mice were given either double distilled water or leaf extract of M. piperita orally (1 g/kg b.wt./day) once a day for three consecutive days, and after 30 min of treatments on the third day were exposed to 8 Gy gamma radiation. Mice were autopsied at 12, 24, 48 hrs and 5, 10 and 20 days post-irradiation to evaluate the percentage of bone marrow cells, frequency of micronuclei and erythropoietin level in serum. An exposure to gamma radiation resulted in a significant decline in the number of bone marrow cells such as leucoblasts, myelocytes, metamyelocytes, band/stab forms, polymorphs, pronormoblasts and normoblasts, lymphocytes, and megakaryocytes. Pretreatment with leaf extract of M. piperita followed by radiation exposure resulted in significant increases in the numbers of leucoblasts, myelocytes, metamyelocytes, band/stab forms, polymorphs, pronormoblasts and normoblasts, lymphocytes, and megakaryocytes in bone marrow as compared to the control group. Pretreatment with leaf extract of M. piperita followed by radiation exposure also resulted in significant decreases in micronucleus frequencies in bone marrow of Swiss albino mice. A significant increase in erythropoietin level was observed at all the studied intervals in leaf extract of M. piperita pretreated irradiated animals as compared to control animals (radiation alone). The results of the present investigation suggest the protective effects of leaf extract of M. piperita against radiation induced hematopoietic damage in bone marrow may be attributed to the maintenance of EPO level in Swiss albino mice.

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Influence of different radioprotective compounds on radiotolerance and cell cycle distribution of human progenitor cells of granulocytopoiesis in vitro

Cited by 6 publications

References 46 publications

Synthesis and Characterization of Two Chiral Pyrrolyl α-Nitronyl Nitroxide Radicals and Determination of their Cytotoxicity and Radioprotective Properties in C6 Cells and Mice under Ionizing Radiation

Synthesis and Characterization of Two Chiral Pyrrolyl α-Nitronyl Nitroxide Radicals and Determination of their Cytotoxicity and Radioprotective Properties in C6 Cells and Mice under Ionizing Radiation

Therapeutic and Clinical Applications of Nitroxide Compounds

Protection Against Radiation Induced Hematopoietic Damage in Bone Marrow of Swiss Albino Mice by Mentha piperita (Linn)

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