ABSTRACT
In adult male C57BL/6 mice with high (HR) and low (LR) resistance to hypoxia, morphological features of colon tumors and blood parameters were evaluated 70 days after intraperitoneal injection of azoxymethane and subsequent consumption of 3 cycles of dextran sulfate sodium. On macroscopic analysis, tumors were found in the distal colon in 35% (7 of 20 animals) of HR and 31% (4 of 13 animals) of LR animals. Microscopic analysis of the distal colon revealed tumors in 75% (15 of 20 animals) of HR and 69% (9 of 13 animals) of LR mice. The tumors were presented by areas of glandular intraepithelial neoplasia and adenocarcinomas; the incidence and the area of the tumors did not differ in groups of HR and LR mice. The number of neuroendocrine and goblet cells in the distal colon mucosa in the areas of tumors was similar in the compared groups. However, in both HR and LR mice of the experimental groups, the content of goblet cells in tumors was lower and the content of endocrine cells was higher than in the corresponding control groups. In the peripheral blood, the erythrocyte count and hemoglobin content decreased in HR and LR mice of the experimental groups; the relative number of monocytes increased only in HR mice and the absolute number of lymphocytes and monocytes decreased in LR mice. Thus, 70 days after azoxymethane administration and dextran sulfate sodium consumption, the tumors in mice were presented by glandular intraepithelial neoplasia and adenocarcinomas, and their incidence and area did not differ between animals with different tolerance to hypoxia.
Subject(s)
Adenocarcinoma , Azoxymethane , Colonic Neoplasms , Dextran Sulfate , Mice, Inbred C57BL , Animals , Mice , Colonic Neoplasms/pathology , Colonic Neoplasms/chemically induced , Colonic Neoplasms/metabolism , Male , Dextran Sulfate/toxicity , Azoxymethane/toxicity , Adenocarcinoma/pathology , Adenocarcinoma/chemically induced , Adenocarcinoma/metabolism , Hypoxia/pathology , Colon/pathology , Goblet Cells/pathology , Goblet Cells/metabolism , Intestinal Mucosa/pathology , Hemoglobins/metabolism , Monocytes/pathology , Monocytes/metabolism , Erythrocyte CountABSTRACT
Morphological, molecular, and biological features of the systemic inflammatory response induced by LPS administration were assessed in adult and old male Wistar rats with high and low resistance to hypoxia. In 6 h after LPS administration, mRNA expression levels of Hif1a, Vegf, Nfkb, and level of IL-1ß protein in old rats were higher than in adult rats regardless of hypoxia tolerance. The morphometric study showed that the number of neutrophils in the interalveolar septa of the lungs was significantly higher in low-resistant adult and old rats 6 h after LPS administration. Thus, in old male Wistar rats, systemic inflammatory response is more pronounced than in adult rats and depends on the initial tolerance to hypoxia, which should be considered when developing new approaches to the therapy of systemic inflammatory response in individuals of different ages.
Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit , Hypoxia , Interleukin-1beta , Rats, Wistar , Animals , Male , Rats , Hypoxia/metabolism , Hypoxia/genetics , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Lipopolysaccharides/pharmacology , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , NF-kappa B/metabolism , NF-kappa B/genetics , Lung/pathology , Lung/metabolism , Lung/drug effects , Lung/immunology , Neutrophils/metabolism , Neutrophils/immunology , Inflammation/metabolism , Inflammation/pathology , Age Factors , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
Morphological and molecular biological features of LPS-induced systemic inflammatory response were assessed in old male Wistar rats with high (HR) and low (LR) resistance to hypoxia. The systemic inflammatory response was modeled by intraperitoneal injection of E. coli O26:B6 LPS; the animals were sacrificed after 6 h. In histological sections, the number of neutrophils in the interalveolar septa and the area of necrosis in the liver were determined. The expression levels of Hif1a, Hif2a, Nfkb, Vegf, Il1b, Il6, Il10, and Tgfb mRNA in the liver and serum concentrations of HIF-1α and IL-1ß were determined. In 4-6 h after LPS injection, 3 (43%) of 7 HR rats died, whereas no deaths were observed among LR rats. At 6 h after LPS injection, the number of neutrophils in the interalveolar septa of the lungs in LR rats was significantly higher than in HR rats, while the area of necrosis in the liver did not differ. At the same time, the mRNA expression levels of the proinflammatory cytokine genes Il1b and Il6 increased in the liver of both HR and LR rats, whereas the expression of Il10 increased only in HR rats. The expression of the Hif1a gene in the liver was higher in LR rats, but the content of HIF-1α protein in blood serum was higher in HR animals. These data should be taken into account when developing new approaches to the therapy of systemic inflammatory response in infectious and inflammatory diseases in the elderly.
