Ungurianu Anca, Margina Denisa, Borsa Claudia, Ionescu Cristina, von Scheven Gudrun, Oziol Lucie, Faure Philippe, Artur Yves, Bürkle Alexander, Gradinaru Daniela, Moreno-Villanueva Maria
Department of Biochemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, RO-020956 Bucharest, Romania.
Department of Biology of Aging, Ana Aslan National Institute of Gerontology and Geriatrics, RO-011241 Bucharest, Romania.
Oxid Med Cell Longev. 2020 Jun 24;2020:3580934. doi: 10.1155/2020/3580934. eCollection 2020.
Ionizing radiation induces genomic instability in living organisms, and several studies reported an ageing-dependent radiosensitivity. Chemical compounds, such as scavengers, radioprotectors, and modifiers, contribute to reducing the radiation-associated toxicity. These compounds are often antioxidants, and therefore, in order to be effective, they must be present before or during exposure to radiation. However, not all antioxidants provide radioprotection. In this study, we investigated the effects of procaine and of a procaine-based product Gerovital H3 (GH3) on the formation of endogenous and X-ray-induced DNA strand breaks in peripheral blood mononuclear cells (PBMCs) isolated from young and elderly individuals. Interestingly, GH3 showed the strongest radioprotective effects in PBMCs from young subjects, while procaine reduced the endogenous amount of DNA strand breaks more pronounced in aged individuals. Both procaine and GH3 inhibited lipid peroxidation, but procaine was more effective in inhibiting mitochondria free radicals' generation, while GH3 showed a higher antioxidant action on macrophage-induced low-density lipoprotein oxidation. Our findings provide new insights into the mechanisms underlying the distinct effects of procaine and GH3 on DNA damage.
电离辐射会在生物体内诱发基因组不稳定,多项研究报告了衰老依赖性放射敏感性。诸如清除剂、辐射防护剂和调节剂等化合物有助于降低辐射相关毒性。这些化合物通常是抗氧化剂,因此,为了发挥作用,它们必须在辐射暴露之前或期间存在。然而,并非所有抗氧化剂都能提供辐射防护。在本研究中,我们调查了普鲁卡因和一种基于普鲁卡因的产品杰诺维药(GH3)对从年轻人和老年人中分离出的外周血单核细胞(PBMC)中内源性和X射线诱导的DNA链断裂形成的影响。有趣的是,GH3在年轻受试者的PBMC中显示出最强的辐射防护作用,而普鲁卡因在老年个体中更显著地减少了内源性DNA链断裂的数量。普鲁卡因和GH3均抑制脂质过氧化,但普鲁卡因在抑制线粒体自由基产生方面更有效,而GH3对巨噬细胞诱导的低密度脂蛋白氧化表现出更高的抗氧化作用。我们的研究结果为普鲁卡因和GH3对DNA损伤的不同影响背后的机制提供了新的见解。