Production of nitrogen oxide derivatives under the influence of NO-synthase inhibitors and natural compounds in mice with transplanted tumors

Abstract

Aim: The aim of the present study was to investigate the dynamics of nitric oxide derivative (NOD) formation in mice with transplanted tumors and to analize whether synthetic NO-synthase inhibitors, NO-donors and natural compounds could modulate NOD synthesis. Materials and Methods: In the study F1(C57BlxCBA), CBA/Lac, BDF and Balb/c mice were used. Endogenous NOD synthesis in mice with transplanted Ehrlich carcinoma (EC) and Lewis lung carcinoma (LLC) was estimated by measuring urine nitrates (NA) and nitrites (NI) excretion and their concentration in tumor tissue determined by cadmium-reduction method. Results: It is shown that EC development is accompanied by increased endogenous NOD formation whereas LLC growth — by its decrease. Total NOD excretion with urine in EC-bearing mice during tumor development was in the range of 1.1x10–7-7.0x10–6 mol/kg body weight that was 1.7–6.8 times higher than that in LLC-bearing mice. Treatment of EC-bearing animals with Nώ-nitro-L-arginine and aminoguanidine resulted in decreased NOD formation causing moderate tumor growth retardation. Effect of treatment with nitroprusside was shown to be dependent on the rout of its administration and dosage. Treatment of EC-bearing mice with picnogenol, tannic acid, spirulina and paprika enriched with selenium resulted in tumor growth inhibition at the early stage of EC growth accompanied by stimulation of endogenous NOD formation. Conclusion: Regulation of endogenous NOD formation towards normal physiological levels or hyperproduction of these compounds may result in tumor growth suppression.