Investigation of Cytostatic Activity of the Methenamine Silver in Vitro and in Vivo

Abstract

Objective: Developing of novel pharmaceutical agents is an actual topic for chemotherapy. Heavy metals possess significant cytotoxic properties and some of them are widely introduced in medical practice, e. g. cisplatin.Methods: Silver salt of methenamine was suggested as prospective substance and tested was tested on black-motley cattle with bovine leukemia to reveal influence on haematological parameters. The preparation was applied in form of 0.5% solution in different doses and was administered as a single intravenous injection. Blood parameters were determined by triple haematological monitoring. Investigation of cytostatic activity was conducted on the leukemic cells of HUT-102 line in vitro in the concentration range of 0.03-3.0 mg/ml. Results:The results showed normalization of blood parameters in a dose-dependent manner after intravenous injection of methenamine silver salt. It was revealed a pronounced inhibitory effect of the silver-based drug on the leukemic cells both in vitro and in vivo. Control blood test one month after experimental therapy confirmed the stability of the achieved results. Conclusion:The tested drug showed a moderate cytostatic effect. Methenamine silver nitrate can be considered as prospective pharmacological agent. Bovine leukaemia was shown as a convenient model for the development of new treatment of blood diseases. Continuation of the work is of interest for both veterinary and medical pharmacotherapy. Designing of novel cytostatic agents for leucosis treatment is a challenging task for modern pharmacology and medicine. Especially acute problem is a resistant form of decease [1][2]. A lot of modern approaches are used now for development delivery systems and screening of novel agents, e. g. virtual ligand screening [3][4]. Due to drug-resistivity, recently interest revived in the metal preparations of a new generation with cytostatic, antiviral and antibacterial activities [5][6][7][8]. Malignant and infectious diseases is a huge problem in veterinary practice as well, e. g. bovine leucosis causing enormous economic losses, and required new eradication approaches [9][10]. Currently, there are well-developed methods of laboratory diagnosis of bovine leukemia [11], but methods of treatment are not developed at all. Specific prophylaxis is only developed, but not introduced [12]. Bovine leukemia virus (BLV) is a retrovirus closely related to the human T-lymphotropic virus type 1 HTLV-I. Bovine leukemia virus (BLV) is a valuable model system for investigation of human lymphotropic viruses [13]. Here we considered viral bovine leukemia as a very convenient model for testing of promising antiviral and cytostatic agents for the medical practice, where leukemia is still a major problem [14]. The aim of this work is to study the cytostatic activity of stabilized solution of methenamine silver nitrate under in vitro and in vivo conditions. Previously, it was shown a wide range of anti-infective activity of methenamine silver nitrate [15].Investigation of antiblastic activity o...