[Combined action of binase and bleomycin toward human lung adenocarcinoma cells]. / Sochetannoe deistvie binazy i bleomitsina na kletki adenokartsinomy legkikh cheloveka.

Some microbial ribonucleases (RNases) demonstrate selective cytotoxic effect against a wide range of tumor cells. In this context combined use of cytotoxic RNases in complex therapy with other chemotherapeutic agents appears to be especially promising. In this study we have investigated the apoptosis-induced effect of Bacillus pumilus RNase (binase) in combination with known anti-tumor antibiotic bleomycin on human lung adenocarcinoma A549 cells. The combined effect of high concentrations of these agents did not have any mutual increase in their apoptosis-induced action, while a combination of non-apoptotic concentrations resulted in the increase of the proportion of apoptotic cells up to 22% as compared with individual effect of bleomycin (6%) and binase (12%) used separately. These results indicate that binase and bleomycin are effective in combination of their low concentrations and ineffective in combination of their high concentrations.

[EFFECT OF MELATONIN ON THE GLUTATHIONE ANTIOXIDANT SYSTEM ACTIVITY IN RAT TISSUES UNDER CONDITIONS OF EXPERIMENTAL RHEUMATOID ARTHRITIS.]

The influence of melatonin on the reduced glutathione content, activity of glutathione peroxidase, glutathione reductase, and glutathione transferase in blood serum, heart, liver, and skeletal muscle of rats under conditions of experimental rheumatoid arthritis development has been estimated. A change in these parameters toward normal control values under the action of hormone has been revealed. The results can be related to realization of the melatonin antioxidant and protective properties under conditions of oxidative stress accompanying the development of rheumatoid arthritis.

[Effect of Bacillus pumilus ribonuclease on the paramagnetic centers of microbial cells].

Potential clinical application of Bacillus pumulus cytotoxic ribonuclease (binase) selectively inducing the death of tumor cells makes it imperative to investigate its effect on the normal human microflora. Flow cytometry was used to determine that binase concentration causing the apoptosis of cancer cells had no effect of the viability of Escherichia coli K12. The changes in the paramagnetic centers of E. coli K12 cells in the presence of nontoxic binase concentrations revealed by EPR spectroscopy included higher EPR signals from iron-containing proteins (including those from the Fe-S clusters) and of the Mn(II) hyperfine structure. The TMTH spin probe (N-(1-hydroxy-2,2,6,6-tetramethylpiperidine-4-il)-2-methylpropanamide hydrochloride) was used to reveal a twofold increase in the levels of reactive oxygen species (ROS) in the cells, which induced oxidative stress in the enzyme-treated bacteria. Inductively coupled plasma mass spectrometry revealed elevated contents of alkaline (Li, Na, K), alkali earth (Mg, Ca), transition (Cr, Mn, Fe, Cu, Zn), and post-transition metals (Bi, Pb) in the cells. Elevated levels of Cu and Zn (which impair the activity of the respiratory chain enzymes) and of Mn, which is known as a superoxide dismutase cofactor, confirmed development of the oxidative stress in bacteria.

[The influence of N-[imino(1-piperidinyl)methyl]guanidine and N-[imino(4-morpholinyl)methyl]guanidine on citrate content, aconitase and citrate synthase activities at ischemia-reperfusion of rats brain].

The influence of some guanidine derivatives on the level of brain citrate, brain activities of aconitase and citrate synthase has been investigated in rats subjected to ischemia-reperfusion. Administration of N-[imino(1-piperidinyl)methyl]guanidine and N-[imino(4-morpholinyl)methyl]guanidine resulted in changes of specific activities of aconitase and citrate synthase towards control values. Under these conditions the citrate level considerably decreased versus rats with untreated ishemia-reperfusion. Treatment with these compounds also decreased the degree of DNA fragmentation markedly increased in rats with ischemia-reperfusion.

[The influense of guanidine derivatives on free radical oxidation intensity and aconitase activity at development of brain ischemia-reperfusion at rats].

The study of some guanidine derivatives influence on free radical oxidation intensity and aconitase activity during the development of brain ischemia-reperfusion at rats has been carried out. The biochemiluminescence parameters increasing at the brain pathology changed toward normal values under the influence of N-[4-(chlorbenzoyl)benztiazol-2-yl]guanidine, N-[imino(1-piperidinyl)methyl]guanidine and N-[imino(4-morpholinyl)methyl]guanidine. The aconitase specific activity decreased in brain and blood of animals with ischemia-reperfusion. Administration of guanidine derivatives during brain ischemia-reperfusion development increased aconitase specific activity. These results suggest that investigated substances can play a role of neuroprotectors, preventing free radical oxidation development.

Effects of lipoic acid on citrate content, aconitate hydratase activity, and oxidative status during myocardial ischemia in rats.

The effects of lipoic acid on intensity of free radical reactions, citrate content, and aconitate hydratase during myocardial ischemia have been investigated. Treatment with lipoic acid normalized biochemiluminescence parameters and citrate level, which were increased in the myocardial pathology. Treatment with lipoic acid also increased specific activity of aconitate hydratase, which was decreased in myocardium and blood of animals with myocardial ischemia. Administration of lipoic acid decreased DNA fragmentation observed during myocardial ischemia. The data suggest that lipoic acid can be effectively used as a cardioprotector preventing the development of free radical oxidation during myocardial ischemia.

[Thioctic acid action on glutathione-dependent antioxidant system functioning at toxic hepatitis of rats].

The effect of thioctic acid on the glutathione dependent antioxidant system and activities of enzymes, generating NADPH of rats has been investigated in rats under conditions of toxic hepatitis. Injections of thioctic acid to animals with toxic hepatitis caused the decrease of glutathione reductase and peroxidase activities to the normal level. Reduced glutathione content also tended to the control level. Administration of thioctic acid to rats with toxic hepatitis also caused the decrease of NADP-dependent isocitrate dehydrogenase and glucose-6-phosphate dehydrogenase which might be associated with decreasing need of NADPH supply for glutathione dependent antioxidant system. Thus, obtained results have shown that thioctic acid may regulate manifestations of oxidative stress and the state of the glutathione antioxidant system.