The Radioprotective Effect of Procaine and Procaine-Derived Product Gerovital H3 in Lymphocytes from Young and Aged Individuals

Abstract

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.

Procaine–The Controversial Geroprotector Candidate: New Insights Regarding Its Molecular and Cellular Effects

“…The preincubation of Jurkat cells with 2.5, 5.0, and, respectively, 10 mM procaine or GH3 effectively reduced the generation of cell membrane lipoperoxides, but GH3 was more effective than procaine especially at the lowest concentration (2.5 mM), when GH3 prevented lipid peroxidation by 21%, versus only 5% for procaine. At 5 and 10 mM, procaine and GH3 showed similar patterns of antioxidant action [ 29 ].…”

“…Interestingly, at low concentrations (0.25, 0.5, and 1 mM), 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. Concentrations of procaine and GH3 of 3 mM and higher (5 and 10 mM) showed a genotoxic effect as measured by DNA strand breaks formation, using the automated fluorescence-detected alkaline DNA unwinding (FADU) assay [ 29 ].…”

“…The inhibitory effect was substantial at the lowest concentration (0.5 mM), 32% for GH3 and 42% for procaine, and increased in a dose-dependent manner. Both procaine and GH3 inhibited at 10 mM more than 80% of the reactive peroxides production in isolated mitochondria fraction [ 29 ].…”

“…Cellular oxidative stress was evaluated using the thiobarbituric acid reactive substances (TBARS) released in the incubation medium, as oxidative stress biomarker for the global measurement of lipid peroxidation end-products such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). At all the tested concentrations (0.5, 1.0, and 2.0 mM), GH3 significantly decreased TBARS (%), whereas the effect of procaine was lower, reaching only half of GH3 effect at 2 mM [ 29 ].…”

“…Although GH3 was internationally launched in 1956, simultaneously with the development of the Free Radical Theory of Aging by Denham Harman [ 21 ], the study of the antioxidant action of procaine and GH3 was documented only after 1980, in various experimental designs, which proved its capacity of limiting the generation of reactive oxygen species (ROS) and lipid peroxidation [ 22 – 29 ]. Recently, the radioprotective effects of procaine and GH3 were reported in vitro in human lymphocytes isolated from young and aged individuals [ 29 ]. Besides its antioxidant, cytoprotective, anti-inflammatory, and antiatherogenic effects, at cellular and molecular levels, procaine has multiple targets, supporting a large number of potential “geroprotective” effects [ 30 , 31 ].…”