Evaluation of Neuroendocrine and Immunological Parameters in Animals Following Chronic Combined Exposure to Xenobiotics

Abstract

Background: A high prevalence of chromium and benzene compounds in the environment associated with motor vehicle and industrial operations arouses interest in the study of these xenobiotics in a long-term experiment. The objective of this work was to analyze effects of a chronic combined exposure to chromium and benzene on the hypothalamic-pituitary-adrenocortical (HPA) and immune systems of male Wistar rats. Materials and methods: Eighty male Wistar rats were administered potassium dichromate and benzene with drinking water in doses equaling one maximum permissible concentration (MPC) during 135 days. The hypothalamus, pituitary gland, adrenal glands, thymus, and spleen were then studied using morphometric, histological, and electron microscopy methods. The streptavidin-biotin peroxidase method was used to determine the expression of pro-apoptotic protein p53 and anti-apoptotic protein bcl2. We also measured the body, thymus and spleen weights of animals, nucleated cell counts in the thymus, spleen, and bone marrow and evaluated the cellular composition of the spleen and bone marrow as well as spontaneous and concanavalin A-induced secretion of interferon gamma (IFN-γ), IL-4, IL-6, and IL-10 cytokines by splenocytes. Results: We established an adverse effect of the exposure on the HPA function expressed in the activation of its secretory activity, blocking the release of hypothalamic neuropeptides at the level of the neurohypophysis and leading to ultrastructural damage to the neurosecretory cells of the hypothalamus, pituitary adenocytes and adrenal cortical cells, as well as in an increase in the programmed death of thymocytes. We also observed a decrease in the thymus weight and thymocyte counts and a complex of structural and functional changes indicating the status of its accidental involution in the exposed rats. The revealed decrease in the splenocyte count in the experimental group was accompanied by an increase in the size of the white spleen pulp. An increase in the induced production of the main immunoregulatory cytokines IFN-γ and IL-4 by splenocytes was found. Conclusion: Our findings can be used to analyze impairments of the HPA and immune systems in workers with a chronic combined exposure to benzene and chromium compounds in the occupational setting.