Assessment of the combined effects of chromium and benzene on the rat neuroendocrine and immune systems

Alexander Viktorovich Karaulov, Alexander Ivanovich Smolyagin, Irina Valeryevna Mikhailova, Alexander Abramovich Stadnikov, Evgenia Vyacheslavovna Ermolina, Yulia Vladimirovna Filippova, Natalia Aleksandrovna Kuzmicheva, Zacharenia Vlata, Aleksandra Buha Djordjevic, Christina Tsitsimpikou, Thomas Hartung, Antonio F. Hernandez, Aristidis Tsatsakis

Research output: Contribution to journalArticlepeer-review


This study assessed the hypothalamic-pituitary-adrenocortical (HPA) axis and lymphoid organs (thymus, spleen, and bone marrow) of Wistar rats treated with a mixture of chromium and benzene. Animals were assessed at three time-points (45, 90 and 135 days) following oral mixture exposure. The hypothalamus-pituitary system was examined in light and electron microscopy. Lymphoid organs underwent a morphological assessment and the immunophenotype of splenocytes was characterized immunohistochemically using monoclonal antibodies. Splenocytes cytokine production of was determined by ELISA after Con-A stimulation. Combined exposure to chromium and benzene in average doses of 20 mg Cr (VI)/kg body weight/day and 0.6 ml benzene/kg body weight/day impaired the responsiveness of the central compartment of the HPA axis, as evidenced by functional activation of the secretory activity of the hypothalamus and pituitary gland, which was not followed by a sufficient extrusion of nonapeptides at the neurohypophysis and hypothalamic median eminence. Chromium and benzene exposure reduced the thymus mass, thymocytes count, and caused a number of structural and functional changes indicative of transient thymus involution. In the spleen, exposure to both chemicals resulted in lymphoreticular hyperplasia and plasma cell-macrophage transformation (also observed in lymph nodes). Apoptosis of thymocytes and lymphocytes was also observed in T-zones of the spleen. Notably, the effects were similar to those observed earlier for the single agents, under the same experimental conditions, without evidence of additivity.

Original languageEnglish (US)
Article number112096
JournalEnvironmental research
StateAccepted/In press - 2021


  • Chemical mixtures
  • Hypothalamic-pituitary-adrenal (HPA) axis
  • Immune system toxicity
  • Lymphoid organs
  • Neuroendocrine system

ASJC Scopus subject areas

  • Biochemistry
  • Environmental Science(all)


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