1Institute of Theoretical and Experimental Biophysics RAS.Pushchino, Russia,
2Pushchino State Institute of Natural Sciences
Recently, there has been an increased interest in natural flavonoid antioxidants, dihydroquercetin (DHQ) in particular. DHQ is known as a vigorous antioxidant, which permits it to be used in treating various pathologies related to ROS hyperproduction, including malignant processes. In pathological states of this kind, increased ROS concentrations induce an increase in nitrogen oxide (NO) production and development of a nitrosative stress in the blood plasma of tumor bearer. However, the effect of flavonoids on the balance of NO metabolites is poorly known.
The aim of this investigation was to elucidate the influence of DHQ on the development of a nitrosative stress in the blood plasma upon in vivo tumor growth.
A Zeidel ascites hepatoma transplanted to the abdominal cavity of Vistar rats was used as a model of tumor growth. Changes in the concentrations of NO metabolites, such as nitrates/nitrites, S-nitrosothiols, and nitrotyrosine were studied in two compartments – in tumor bearer blood plasma and ascites.
In the blood plasma, a significant increase in the nitrosylaing stress manifested as a growth of the low-molecular nitrite/nitrate concentration (3-4 times) and a strong NO-dependent protein modification associated with accumulation of S-nitrosothiols and nitrotyrosine. These processes are likely to be due to that DHQ is able to activate the synthesis of nitrogen oxide by endothelial cells by means of increasing the level of intracellular calcium. On the other hand, DHQ injections to the abdomen did not cause any significant changes in the level of NO metabolites in the ascites. In the area of tumor growth there are no sources of nitrogen oxide other than activated macrophages and the transport of modified proteins from the plasma. Besides, as it is evident from the literature, DHQ is capable of inhibiting NO synthesis by macrophages. These data explain the low level of NO metabolites in the region of tumor growth. The results of the present study permit the conclusion that DHQ offers promise as a compound capable of activating the synthesis of nitrogen oxide in endothelial cells and thus participating in regulation of blood pressure.
This work was supported: FTsP «Scientific and scientific- pedagogical staff of innovative Russia» on 2009 - 2013годы, the agreement: 14.B37.21.1120; statetasks to higher educational institutions on 2013-2015, the code number: 4.3508.2011.