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

Abstract

To assess oxidative stress and structural changes of the serum albumin in rats with transplanted Walker-256carcinosarcoma (W256) strains with varying sensitivity to doxorubicin (Dox). 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. On the 9th day after W256transplantation a significant increase in the leukocyte counts was observed in the groups of animals with the Dox-resistant and parental (Dox-sensitive) W256tumors compared with the group of the intact animals: up to 14.24 ± 1.92•103/μl and 9.78 ± 1.03•103/μl, vs 8.92 ± 1.04•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. The development of transplanted Walker-256carcinosarcoma, 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.