A comparative assessment of the effects of alkaloid tryptanthrin,rosmarinic acid,and doxorubicin on the redox status of tumor and immune cells

A comparative study of the effects of natural compounds with different biological activity spectra and mechanisms of action on the dynamics of the change in the redox-status of tumor and immune cells was carried out by measuring the intracellular level of reactive oxygen species depending on the dose and incubation time. The quinazoline alkaloid tryptanthrin, phenol propanoid rosmarinic acid, and the anticancer agent doxorubicin were tested. This study was performed on Ehrlich adenocarcinoma tumor cells and splenocytes after loading with the oxidant sensing fluorescent probe 2′,7′-dichlorofluorescein diacetate. It was shown that when rosmarinic acid influences tumor cells it has a pronounced antioxidant activity at a low dose (1 mg/mL), while a high dose of rosmarinic acid (10 mg/mL) exhibits prooxidant activity. Interestingly, in a splenocyte cell culture, rosmarinic acid reduced the level of reactive oxygen species at low and high doses. The combined application of doxorubicin with rosmarinic acid at a low dose reduced the prooxidant effect of doxorubicin, which is a potent inducer of reactive oxygen species in tumor cells. Tryptanthrin is also a potent inducer of reactive oxygen species with respect to tumor and immune cells; it is a more potent prooxidant than doxorubicin. In addition, tryptanthrin enhanced the doxorubicin-induced formation of reactive oxygen species by tumor cells in the combined use of doxorubicin with tryptanthrin. However, the prooxidant effect of tryptanthrin is short-term and decreases after a prolonged incubation. The effect of reactive oxygen species on the potent mechanisms of the biological activities of the individual and combined substances under study is discussed.     

Actual Problems of Evolutionary Immunology

Problems of evolution of adaptive immunity system which has arisen in vertebrate animals in addition to inherited from invertebrates innate immunity system are considered. The question how the ineffective system of adaptive immunity of the lower vertebrates could be the object of positive selection is discussed. The attention is paid to three aspects of the problem. (1) Adaptive immunity system was formed not only in contact with pathogens, but also on the background of coexistence with genetically foreign organisms, i.e., under conditions of symbiosis which itself is the powerful factor of evolution and gives an organism no less advantages in selection than is given by protection from pathogens. (2) Many kinds of activity of the adaptive immunity system are not protective by their nature. These are the ability of an organism to maintain tolerance to its own tissues, unresponsiveness against food components and bacterial flora, against alloantigens in pregnancy and in the chimerism state. Thus, the immune system alongside with protective has also another function that could be called acceptive. (3) In vertebrate ontogenesis the emergence of the acceptive function occurs ahead of protective mechanisms of adaptive immunity. This allows assuming that the acceptive function was the first to appear and develop. The protective function emerged later and developed as a realization of the opportunities peculiar to the former of these functions. From this point of view, immunity should be defined as a mechanism of maintenance of internal environment constancy by means of restriction of expansion of the genetically foreign material and by means of establishment of symbiotic relations with it.     

Autoaggressive immunocompetent cells in the bodies of mice at remote periods following irradiation]

Lethally irradiated DBA/l mice or (C57Bl X DBA/l1 F1 hybrid mice were injected with therapeutically effective doses of isologous bone marrow cells; simultaneously syngeneic lymph node cells from either intact (control) animals or mice survived after sublethal irradiation were transplanted. In control the viability of the recipients was not affected by the presence of lymphoid cells in the mixed transplant. In contrast, the beneficial action of the bone marrow cells was abolished (killing-effect) by the lymphoid cells from mice sacrificed 6 to 12 months after the irradiation (600--700 r). The manifestation of the killing-effect depended on the number of the transplanted lymphoid cells and on the dose of the bone marrow cells in the transplant. The killing-effect was not revealed when the lymphoid cells were obtained from the donors on the 30th day after irradiation. The results suggest the autosensitization of the organism at the late postirradiation periods.     

Defining the optimal conditions for immunoperoxidase cytochemistry at the submicroscopic level]

The authors tested a number of experimental protocols and chemicals known to facilitate permeabilization of tissues to immunoperoxidase markers without ultrastructural alterations of the cells to be examined. Monoclonal antibodies producing hybridoma lymphomas served as a primary test object. None of the procedures employed (i.e., quenching of the fixative aldehydes by some reducing agents; cryopermeabilization; treatment by detergents) were shown either to intensify stainability or to increase the penetration of immunoreagents into the tissue depth. The diffusion efficiency depended only on the marker molecular mass and the thickness of the vibratome section incubated. The Elder and coworkers (1983) two-step technique has been found superior in the preservation of both immunoreactivity and fine structure of the cell.     

Mechanisms of Participation of the Urokinase Receptor in Directed Axonal Growth

Molecular Biology - The degradation of the extracellular matrix plays an important role in the processes of morphogenesis, angio- and neurogenesis, wound healing, inflammation, carcinogenesis and...