Molecular Energotropic and Cellular Mechanism of the Radioprotective Action of Sulfur-Containing Biphenolic Dibasic Acids under Conditions of Lethal γ-Irradiation.

Dibasic acids (DBA) with benzene rings having substituents and connected by a sulfurcontaining bridge exhibited radioprotective effectiveness when administered in non-toxic concentrations to laboratory mice 1 h before γ-irradiation in a lethal dose of 8 Gy. The correlation of protonophore activity on bilayer lipid membranes with radioprotective (in mice) and uncoupling activity (in mitochondria) indicates a molecular protonophore uncoupling radioprotective mechanism of DBA action on mitochondria, which manifests in temporary partial inhibition of energy production. The effectiveness of DBA depends on the position and the degree of dissociation of OH-groups and increased in the presence of a sulfur-containing bridge and substituents in the series Br->Cl->NO2->COOCH3->COOH-. The higher radioprotective effect was observed for more effective uncouplers of the processes of oxidative phosphorylation and respiration of mitochondria, DBA1 preparations with OH-groups in the 2nd position of the benzene rings (80-100%), than for DBA2 with OH- in the 4th position (40-60%). The radioprotective effect of DBA was related to their antioxidant activity during and after irradiation to a lesser extent than with their uncoupling efficiency. At the cellular level, the radioprotective mechanism of DBA is related to temporary hypoxia and inhibition of metabolism leading to inhibition of generation of ROS, radicals, and LPO products.