Pindolol ((2RS)-(1-(1H-indol-4-iloxy)-3- [(1-metyloetylo)amino]-2-propanol) in substantia was exposed to ionising radiation emitted by high energy electrons from an accelerator, in the standard sterilisation dose of 25 kGy and in higher doses from the range 50–400 kGy. The effects of irradiation were checked by spectrometric methods (UV, MS, FT-IR, EPR) and hyphenated methods (HPLC-MS) and the results were referred to those obtained for non-irradiated sample. EPR results indicated the presence of free radicals in irradiated samples, in the amount of 1.36 × 1016 spin g−1 for 25 kGy and 3.70×1016 spin g−1 for 400 kGy. The loss of pindolol content determined by HPLC was 1.34% after irradiation with 400 kGy, while the radiolytic yield of the total radiolysis for this dose of irradiation was 2.69×107 mol J−1. By means of HPLC-MS it was possible to separate and identify one product of radiolytic decomposition, which probably is 2-((R)-3-(1H-indol-4-yloxy)-2-hydroxypropylamino)propan-1-ol formed upon oxidation. In the range of sterilisation doses (25–50 kGy), pindolol was found to show high radiochemical stability and would probably be safely sterilised by the standard dose of 25 kGy. [...]
The free radical theory of aging suggests that aging is caused by accumulation of damage inflicted by reactive oxygen species (ROS). However, this concept has been very useful in defining the contribution of oxidative damage to the aging process, an increasing number of studies opposes it. The idea that oxidative damage represents only one of many causes of aging also has limitations, as it does not explain causal relationships and inevitability of damage accumulation. Here, it is discussed that heterogeneity, infidelity and imperfectness of each and every biological process may be responsible for the inevitable accumulation of by-products and other damage forms. Although ROS are prototypical by-products, their contribution to aging is governed by the metabolic organization of the cell, its protective systems, and genotype. These factors are controlled by natural selection, dietary and genetic interventions that extend lifespan, change the composition of cumulative damage and the rates of accumulation of its various forms. Oxidative damage, like other specific damage types viewed in isolation or in combination, does not represent the cause of aging. Instead, biological imperfectness, which leads to inevitable accumulation of damage in the form of mildly deleterious molecular species, may help define the true root of aging. Free radical and other specialized damage theories served their purpose in the understanding of the aging process, but in the current form they limit further progress in this area.
Reactive oxygen species (ROS) may generate different nucleoside/nucleotide radicals in a cell environment. In this study, the possibility of cyclic-2’-deoxyadenosines formation by a rearrangement of their free radicals was investigated. It seems that for cyclic-nucleosides formation, adoption of an O4’-exo conformation by the sugar moiety is necessary. However, this is the energetically unfavoured form of the 2-deoxyribose ring. Moreover, the creation of a O5’, C8 bond in purine deoxy-nucleosides/nucleotides leads to the termination of the DNA elongation process. [...]
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