Lactatemia as a possible pharmacological marker of NOS-inhibitor T1023 induced radioresistance

The aim was to study the dynamics of lactatemia and acid-base balance as a possible indicator of hypoxic and radioprotective effect of the nitric oxide synthase (NOS) inhibitor T1023. The research methods included the assessment of lactate content, blood gases content and acid-base balance of arterial blood and comparison of these data with cardiovascular and radioprotective effects of compound T1023. The results show that the dynamics of lactate content and compensatory shifts in blood gases and acid-base balance, that prevent the development of acidosis, are the results of hypoxic effect of T1023 and such effects clearly correlate with cardiovascular effects that induce transient hypoxia. Comparison of these data with radiobiological effects of T1023 revealed the pronounced correlation between radioprotective effect of this compound and induced by it lactatemia. At the same time, the revealed correlation is quantitatively described by simple linear models. The obtained data show that hypoxic and radioprotective effects of NOS-inhibitor T1023 that change over time can be revealed using available laboratory methods. This suggests that lactatemia can be used as a pharmacological marker of changes in biological object's radioresistance. Full verification of such marker could potentially allow T1023 to overcome existing obstacles in the clinical trials of radioprotectors.