Abstract
Alloxan (ALX) and streptozotocin (STZ) are extensively used to induce type 1 diabetes (T1D) in animal models. This study is aimed at evaluating the differences in immune parameters caused by ALX and STZ. T1D was induced either with ALX or with STZ, and the animals were followed for up to 180 days. Both ALX and STZ induced a decrease in the total number of circulating leukocytes and lymphocytes, with an increase in granulocytes when compared to control mice (CT). STZ-treated mice also exhibited an increase in neutrophils and a reduction in the lymphocyte percentage in the bone marrow. In addition, while the STZ-treated group showed a decrease in total CD3+, CD4−CD8+, and CD4+CD8+ T lymphocytes in the thymus and CD19+ B lymphocytes in the pancreas and spleen, the ALX group showed an increase in CD4−CD8+ and CD19+ only in the thymus. Basal levels of splenic interleukin- (IL-) 1β and pancreatic IL-6 in the STZ group were decreased. Both diabetic groups showed atrophy of the thymic medulla and degeneration of pancreatic islets of Langerhans composed of inflammatory infiltration and hyperemia with vasodilation. ALX-treated mice showed a decrease in reticuloendothelial cells, enhanced lymphocyte/thymocyte cell death, and increased number of Hassall's corpuscles. Reduced in vitro activation of splenic lymphocytes was found in the STZ-treated group. Furthermore, mice immunized with ovalbumin (OVA) showed a more intense antigen-specific paw edema response in the STZ-treated group, while production of anti-OVA IgG1 antibodies was similar in both groups. Thereby, important changes in immune cell parameters in vivo and in vitro were found at an early stage of T1D in the STZ-treated group, whereas alterations in the ALX-treated group were mostly found in the chronic phase of T1D, including increased mortality rates. These findings suggest that the effects of ALX and STZ influenced, at different times, lymphoid organs and their cell populations.
Highlights
Diabetes mellitus is a chronic disorder characterized by persistent levels of hyperglycemia caused by an insufficient production of insulin by the β cells of the pancreas due to a destruction of these cells in type 1 diabetes (T1D) or by ineffective insulin action in type 2 diabetes (T2D) [1,2,3]
While the STZ-treated group showed a decrease in total CD3+, CD4-CD8+, and CD4+CD8+ T lymphocytes in the thymus and CD19+ B lymphocytes in the pancreas and spleen, the ALX group showed an increase in CD4-CD8+ and CD19+ only in the thymus
Some animals from the ALX group started to die after 60 days (Figure 1(c)) and presented tumor nodules throughout the body, as it has already been reported by other authors [31,32,33]
Summary
Diabetes mellitus is a chronic disorder characterized by persistent levels of hyperglycemia caused by an insufficient production of insulin by the β cells of the pancreas due to a destruction of these cells in type 1 diabetes (T1D) or by ineffective insulin action in type 2 diabetes (T2D) [1,2,3]. Alloxan (ALX) and streptozotocin (STZ) bind to Mediators of Inflammation the glucose transporter- (GLUT-) 2 receptor, causing cell death by reactive oxygen species (ROS) generation (ALX) or inducing DNA damage (STZ) directly [5]. These diabetogenic agents, may have different toxicological effects depending on the dose and route of administration [6]. Diab et al conducted a similar study to evaluate the cytotoxicity of both agents, finding in vitro changes in blood cell populations, reduction of splenocytes, and immunosuppressive effects on graft transplantation in individuals treated with STZ [10]
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