[The molecular mechanisms of the action of the radioprotector indometafen. The biosynthetic and bioenergetic aspects].
It was shown that indomethaphen (IM) is capable of stimulation of the synthesis of DNA, RNA, and protein precursors in mice. The IM-induced elevated level of the ribonucleotide reductase activity and, hence, deoxyribonucleotide pool in the spleen at the moment of irradiation and during the early postradiation period provides for complete DNA repair. As a result, the damaging effect of ionizing irradiation is weakened. At later stages (2-20 days) IM activates protein and DNA synthesis leading to the recovery of the ribonucleotide reductase activity in the spleen, on increased content of Fe3(+)-transferrin, cytochrome-c-oxidase, and ferrosulfuric components of the mitochondrial electron transport chain, and increased potential of the detoxication system due to the elevated content of cytochrome P-450. IM stimulates ATP synthesis. Thus, IM enhances compensatory-restorative reactions of the cell systems, more pronounced in the spleen than in the liver.
Chernov
G A
GA
Sharygin
V L
VL
Pulatova
M K
MK
Sharf
V G
VG
Borovkov
M V
MV
Shliakova
T G
TG
Khristianovich
D S
DS
Mitrokhin
Iu I
IuI
Todorov
I N
IN
D000818:Animals; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004734:Energy Metabolism / Q000187:drug effects* / Q000528:radiation effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011498:Protein Precursors / Q000096:biosynthesis / Q000187:drug effects* / Q000528:radiation effects; D012313:RNA / Q000096:biosynthesis / Q000187:drug effects* / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D046911:Macromolecular Substances; D011498:Protein Precursors; D011837:Radiation-Protective Agents; C091454:indometafen; D013629:Tamoxifen; D012313:RNA; D004247:DNA
Molekuliarnye mekhanizmy deĭstviia radioprotektora indometafena. Biosinteticheskie i bioénergeticheskie aspekty.