ROLE OF MITOCHONDRIAL NO-SYNTHASE IN THE IMPLEMENTATION OF ANTITUMOR EFFECTS OF POLYUNSATURATED FATTY ACIDS IN THE MODEL OF GUERIN’S CARCINOMA UNDER IN VIVO CONDITIONS

NO-synthase activity and NO level in the mitochondrial fraction of rats Guerin’s carcinoma under conditions of different ю-3 and ю-6 polyunsaturated fatty acids (PUFAs) supplementation has been investigated. Guerin’s carcinoma was used as a cancer model. 0.5 ml of 30% carcinoma cell suspension in normal saline was implanted subcutaneously into thigh of a hind leg. The intensity of tumor growth was evaluated based on measurements of subcutaneous tumor size and coefficient of tumor mass. It was showed that ω-3 PUFAs supplementation before and after transplantation of Guerin’s carcinoma resulted in the decreases of tumor growth and coefficient of tumor mass in an organism. Additional ю-6 PUFA supplementation can stimulate tumor progression and increase tumor mass in body in the logarithmic phases of carcinogenesis as compared to the tumor-bearing rats. The effect depends on duration of ю-3 and ю-6 PUFAs administration and on the level of preliminary provision of an organism with these PUFAs. We found increased NO-synthase activity and NO content in mitochondrial fraction of Guerin’s carcinoma in animals of the group that was administered ю-3 PUFAs both before and post-implantation of the carcinoma during logarithmic phase of carcinogenesis. At the same time, the ю-6 PUFA administration does not contribute to significant changes in the NO-synthase system components in the mitochondrial fraction of Guerin’s carcinoma in comparison with the tumor-bearing rats.</jats:p

The Potential Protective Effect of Oligoribonucleotides-d-Mannitol Complexes against Thioacetamide-Induced Hepatotoxicity in Mice

This study investigated the potential hepatoprotective effect of oligoribonucleotides-d-mannitol complexes (ORNs-d-M) against thioacetamide (TAA)-induced hepatotoxicity in mice. The hepatoprotective activity of ORNs-d-M was evaluated in thioacetamide (TAA)-treated C57BL/6J. Results indicate that treatment with ORNs-d-M displayed a protective effect at the TAA-induced liver injury. Treatment with ORNs-d-M, starting at 0 h after the administration of TAA, decreased TAA-elevated serum alanine aminotransferase (ALT) and &gamma;-glutamyl transpeptidase (GGT). Activities of glutathione S-transferase (GST) and glutathione peroxidase (GPx), and levels of glutathione (GSH), were enhanced with ORNs-d-M administration, while the hepatic oxidative biomarkers (TBA-reactive substances, protein carbonyl derivatives, protein-SH group) and myeloperoxidase (MPO) activity were reduced. Furthermore, genetic analysis has shown that the ORNs-d-M decreases the expression of mRNA pro-inflammatory cytokines, such as tumor necrosis factor &alpha; (TNF-&alpha;) and interleukin-6 (IL-6), profibrogenic cytokine-transforming growth factor &beta;1 (TGF-&beta;1), as well as the principal protein of the extracellular matrix&mdash;collagen I. The present study demonstrates that ORNs-d-M exerts a protective effect against TAA-induced liver injury, which may be associated with its anti-inflammatory effects, inhibition of overexpression of mRNA cytokines, and direct effects on the metabolism of the toxin

Vitamin A and Vitamin E: Will the Real Antioxidant Please Stand Up?

Vitamin A, acting through its metabolite, all- trans-retinoic acid, is a potent transcriptional regulator affecting expression levels of hundreds of genes through retinoic acid response elements present within these genes. However, the literature is replete with claims that consider vitamin A to be an antioxidant vitamin, like vitamins C and E. This apparent contradiction in the understanding of how vitamin A acts mechanistically within the body is a major focus of this review. Vitamin E, which is generally understood to act as a lipophilic antioxidant protecting polyunsaturated fatty acids present in membranes, is often proposed to be a transcriptional regulator. The evaluation of this claim is another focus of the review. We conclude that vitamin A is an indirect antioxidant, whose indirect function is to transcriptionally regulate a number of genes involved in mediating the body's canonical antioxidant responses. Vitamin E, in addition to being a direct antioxidant, prevents the increase of peroxidized lipids that alter both metabolic pathways and gene expression profiles within tissues and cells. However, there is little compelling evidence that vitamin E has a direct transcriptional mechanism like that of vitamin A. Thus, we propose that the term antioxidant not be applied to vitamin A, and we discourage the use of the term transcriptional mediator when discussing vitamin E. </jats:p

Antitumor Activity of Alloy and Core-Shell-Type Bimetallic AgAu Nanoparticles

Abstract Nanoparticles (NPs) of noble metals, namely gold and silver, remain promising anticancer agents capable of enhancing current surgery- and chemotherapeutic-based approaches in cancer treatment. Bimetallic AgAu composition can be used as a more effective agent due to the synergetic effect. Among the physicochemical parameters affecting gold and silver nanoparticle biological activity, a primary concern relates to their size, shape, composition, charge, etc. However, the impact of metal components/composition as well as metal topological distribution within NPs is incompletely characterized and remains to be further elucidated and clarified. In the present work, we tested a series of colloidal solutions of AgAu NPs of alloy and core-shell type for an antitumor activity depending on metal molar ratios (Ag:Au = 1:1; 1:3; 3:1) and topological distribution of gold and silver within NPs (AucoreAgshell; AgcoreAushell). The efficacy at which an administration of the gold and silver NPs inhibits mouse Lewis lung carcinoma (LLC) growth in vivo was compared. The data suggest that in vivo antitumor activity of the studied NPs strongly depends on gold and silver interaction arising from their ordered topological distribution. NPs with Ag core covered by Au shell were the most effective among the NPs tested towards LLC tumor growth and metastasizing inhibition. Our data show that among the NPs tested in this study, AgcoreAushell NPs may serve as a suitable anticancerous prototype