Comparative study of biochemical and morphological parameters in rats with Walker 256 and Walker 256/DOX carcinosarcoma.

AIM: To evaluate the changes of some biochemical blood plasma parameters and morphological structure of the internal organs of rats with transplanted doxorubicin (DOX)-sensitive (Walker 256) and doxorubicin-resistant (Walker 256/DOX) strains of Walker 256 carcinosarcoma. MATERIALS AND METHODS: The study was performed on female Wistar rats with transplanted Walker 256 or Walker 256/DOX and intact animals (control). On the 9th day after transplantation of tumor cells, a comparative analysis of some blood plasma biochemical parameters and morphological examination of the liver, kidneys, myocardium and spleen of rats was carried out. RESULTS: Walker 256 growth, in comparison with Walker 256/DOX, is accompanied by more pronounced systemic effect on tumor-bearing rats. Uric acid concentration in the blood plasma of Walker 256 bearing rats was significantly (by 15.5%) higher than in Walker 256/DOX bearing rats. Aspartate aminotransferase activity in the Walker 256 group was significantly (by 107.2%) higher than in Walker 256/DOX group, but alanine aminotransferase activity was 58.5% lower. 56.7% decrease of alkaline phosphatase in rats with Walker 256, and 21% increase of this index in rats with Walker 256/DOX were observed. The growth of Walker 256 carcinosarcoma led to greater structural damage of the liver, kidneys and spleen in experimental animals compared with Walker 256/DOX strain. CONCLUSION: Tumor growth in rats with Walker 256/DOX leads to less pronounced changes in the biochemical parameters of rat blood plasma and morphological structure of internal organs compared with wild-type carcinosarcoma.

Structural changes of serum albumin in response to oxidative stress caused by Walker-256 carcinosarcoma growth.

AIM: To assess oxidative stress and structural changes of the serum albumin in rats with transplanted Walker-256 carcinosarcoma (W256) strains with varying sensitivity to doxorubicin (Dox). MATERIALS AND METHODS: The study was performed on female Wistar rats with transplanted W256. On the 9th day after tumor cell transplantation an analysis of peripheral blood, oxidative stress parameters, and structural changes of serum albumin of experimental animals was performed. RESULTS: On the 9th day after W256 transplantation a significant increase in the leukocyte counts was observed in the groups of animals with the Dox-resistant and parental (Dox-sensitive) W256 tumors compared with the group of the intact animals: up to 14.24 ± 1.92 â€¢ 103/µl and 9.78 ± 1.03 â€¢ 103/µl, vs 8.92 ± 1.04 â€¢ 103/µl, respectively, due to the increase of granulocyte and monocyte counts. The number of lymphocytes was within the normal range. The level of hemoglobin and the erythrocyte counts were also within normal limits, but hematocrit in both groups of animals with tumors somewhat increased against the background of 1.2-fold elevation of the mean erythrocyte volume. In the group of rats with Dox-resistant W256, there was observed a decrease in the plateletcrit by almost 22% and thrombocyte counts - by 28%. Analysis of oxidative stress indices revealed a significant increase in the level of reactive oxygen species, 2-fold increase of malonic dialdehyde level and the degree of oxidative damage of blood plasma proteins, as well as a decrease in the activity of catalase in hemolysates (by 12-15%) in both groups of tumor-bearing rats. With the use of differential scanning calorimetry, UV and fluorescence spectroscopy we have revealed anomalous conformational changes of albumin caused by tumor development: structural rearrangements in the region of its first drug binding site located in the IIA domain, separation of globular parts of albumin molecule, and partial "opening" in a protein molecular three-domain structure resulting a loss of its thermal resistance. CONCLUSION: The development of transplanted Walker-256 carcinosarcoma, especially its Dox-resistant variant, results in severe metabolic intoxication reflected in alteration of hematological parameters, and indices of oxidative stress, as well as architectonic changes of serum albumin.

Highly activated carbon enterosorbent mediates the suppression of paraneoplastic syndrome associated with Lewis lung carcinoma in mice.

AIM: To investigate the effect of enterosorption on the development of paraneoplastic syndrome in mice with Lewis lung carcinoma (LLC). MATERIALS AND METHODS: The study was performed on male С57/ВL6 mice with transplanted LLC. As an enterosorbent, highly activated powder fraction of HSGD was administered per os daily at a dose of 0.625 g/kg for two weeks starting from the 7th day after tumor cell transplantation. Analysis of hemo- and myelograms, morphological alterations in vital organs, the activities of catalase and superoxide dismutase, biochemical analysis of blood and quantitative analysis of hydroperoxides, malonic dialdehyde, аdvanced oxidation protein products was carried out by standard methods after completing the course of enterosorption. Ligand loading of blood plasma proteins was estimated by the method of differential scanning microcalorimetry. RESULTS: Administration of enterosorbent resulted in inhibition of LLC growth and in nearly 2-fold decrease of lung metastases number (p < 0.05). Activation of granulocytic line in the bone marrow with nearly 3-fold enhancement of mitotic activity took place after enterosorbent administration. Red cell lineage indices and bone marrow cellularity remained unaltered. After enterosorption session, the studied biochemical indices of peripheral blood evidenced on decreasing the endogenous intoxication and oxidative stress levels, improving the functional state of kidneys, increasing the resistance of erythrocyte membranes and lowering the ligand loading of blood plasma transport proteins. Morphological structure of kidneys and liver confirmed significant positive effect of enterosorption. The data of morphologic examination of gastric fundus, small intestine, and large bowel slides after 2-week administration of enterosorbent showed its high safety and proper evacuation from intestine. CONCLUSION: The two-week long enterosorption session in mice with LLC caused the suppression of tumor growth and metastasis, normalization of bone marrow hemopoiesis. Enterosorption exerted a positive influence on the structural-morphologic indexes and regenerative potential of kidneys and liver, mitigated manifestations of oxidative stress, decreased the level of endogenous intoxication, promoted deliganding of albumin molecule and deloading of erythrocyte membranes.

Effect of enterosorption on paraneoplastic syndrome manifestations in mice with highly angiogenic variant of Lewis lung carcinoma.

AIM: To study the correcting effects of microgranulated HSGD enterosorbent on hematological, morphological and biochemical indices of paraneoplastic syndrome in mice with highly angiogenic variant of Lewis lung carcinoma LLC/R9. METHODS: The study was performed on male С57/ВL6 mice with transplanted LLC/R9. Enterosorbent HSGD was administered daily at a dose of 0.625 g/kg for 2 weeks starting from 7(th) day after tumor cell transplantation. When enterosorption was completed, an analysis of peripheral blood, biochemical indices and morphological structure of tumor, lung, liver, spleen and thymus was carried out by standard methods. RESULTS: It has been shown that administration of enterosorbent did not affect LLC/R9 growth but resulted in nearly two fold decrease of the volume of lung metastases (p < 0.05). Erythrocyte number and hemoglobin level were higher by 30.0% (p < 0.05) and 23.3% (p < 0.05), respectively, in mice treated with enterosorbents as compared to untreated animals. In addition sorbent treatment completely normalized the thrombocyte index resulting in elevation of platelet number by 54.5% (p < 0.01) up to their level in intact mice. The morphological examination of liver and biochemical analysis of peripheral blood evidenced on significant positive correcting effect of enterosorption on histological structure of this organ and its functional activity. Normalization of total proteins and serum albumin level as well as significant decrease of total lipid concentration by 29% (p < 0.01) in blood of treated mice were observed. CONCLUSION: Positive influence of microgranulated carbon sorbent on some hematological, morphological and biochemical indices of tumor associated symptoms in LLC/R9-bearing mice denotes that enterosorption-based therapy can be considered as a prospective treatment for correction of some paraneoplastic syndrome signs in cancer patients.

[The central catecholaminergic mechanisms regulating thyroid function in birds]. / Tsentral'ni katekholaminerhichni mekhanizmy rehuliatsiï tyreoïdnoï funktsiï u ptakhiv.

Response of the hypothalamo-hypophyseal-thyroid system of birds to drugs influencing brain catecholaminergic structures was analyzed by means of radioimmunoassay and morphometry. The 12-day- and 60-day-old cockerels were given dopamine precursor (L-DOPA), dopamine-blocking agent (haloperidole) and alpha-adrenoceptor activator (phenylephrine) during 7 days. The results obtained demonstrate that the brain catecholaminergic structures have participated in regulation of the hypothalamo-hypophyseal-thyroid system of birds. The dopaminergic structures have inhibited, the thyroid function while, alpha-adrenergic structures have stimulated it.

[Effects of prostaglandins E2 and F2 alpha on the hypothalamo-hypophyseal-adrenal system and thyroid function in mice with Lewis lung carcinoma]. / Vliianie prostaglandinov E2 i F2 alfa na gipotalamo-gipofizarno-nadpochechnikvuiu sistemu i tireoidnuiu funktsiiu u myshei s kartsinomoi legkogo L'iuis.

It has been determined that prostaglandins E2 and F2 alpha being exogenously inoculated during the premetastatic period to mice with metastatic Lewis lung carcinoma in equal degree activate neurocytes of supraoptic and paraventricular hypothalamus nuclei, playing the important role in secretion of peptidergic hypophysial adrenal gland complex, but they exert unequal influence on pituitary body, adrenal cortex and thyroid apparatus. F2 alpha stimulates the pituitary body corticotrophic function, secretory function of spongiocytes and thyrocytes, identifies the thyroxin and triiodothyronine utilization, E2, on the contrary, does not influence these indices or reduces them. Obviously, the mentioned above differences between E2 and F2 alpha may be explained by their different influences on antimetastatic resistance.