[The role of xanthine oxidase in the cytotoxic action of nitrates and nitrites].
It is established, that in rat organism nitrites and nitrates can be restored in nitrogen oxide due to nitrate and nitrite reductase activity of xanthine oxidase system. The rat thymocytes were shown in the experiment in vitro to have nitrate reductase activity, which was activated by hypoxanthine and inhibited by allopurinol. As a result of thymocytes apoptosis, provoked by papaverine, there is an essential increase of nitrate reductase activity of xanthine oxidase. The comparative research of thymocytes destruction character under the action of sodium nitroprusside (NP), N-nitrosodimethylamine (NDMA), NaNO2 and NaNO3 has been revealed, that their cytotoxicity, is dose-dependent and it decreases in order of these compounds mentioning. Synergism is revealed at the action on thymocytes of NP combined with sodium nitrite. These data as the results of investigation of EPR-spectrometry as well as use of thymocytes, containing a trap--complex of diethyldithiocarbamate-iron (DETK-Fe), allow to assume, that cytotoxic effect of NP is caused by the action of liberated from it. Cytotoxic action of nitrate is connected with reducibility to nitrite which influences on the cells independently, and nitrite action doesn't depend on its transformation to NO. The death of thymocytes caused by N-nitrosodimethylamine is not a result of its denitrozation.
Medved Institute of Ecohygiene and Toxicology, Ministry of Health of Ukraine, Kyiv. dmitr@medved.kiev.ua
N P
NP
Dmitrenko
T O
TO
Kishko
S G
SG
Shandrenko
D000818:Animals; D004128:Dimethylnitrosamine / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D009566:Nitrates / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D013950:Thymus Gland / Q000187:drug effects / Q000201:enzymology; D014969:Xanthine Oxidase / Q000378:metabolism*
D009566:Nitrates; D009573:Nitrites; D009599:Nitroprusside; D014969:Xanthine Oxidase; D004128:Dimethylnitrosamine