Intravenous Administration of Glutamate Ionotropic Antagonists in Healthy Rats, Induces Lymphopenia and Affects Their Hematological Profile

Abstract

Background: Glutamate is one of the primary endogenous amino acids of the Central Nervous System (CNS). Research over the last years has proven the existence of glutamate subunit receptors in additional non-neuronal tissues outside CNS such as the hematopoietic system.The purpose of this paper is to define the possible in vivo effect of glutamate ionotropic antagonists MK-801and NBQX in the hematopoietic system as well as their possible use in the cure of hematopoietic diseases and on their use on patients with co-existing neurological and hematopoietic disorders.

Methods: Glutamate ionotropic antagonists MK-801 and NBQX were administrated intravenously in male wistar rats of 250 - 350 g weight. Animals treated with glutamate antagonists (n = 24) were compared to a control group (n = 10). The following parameters were evaluated 12 h and 24 h after drug administraton: Full blood count with differential, aggregation intensity, plus CD3, CD54 and CD49a expression on T-lymphocytes with flow cytometry. Bone marrow was assessed with bone marrow smears. The results were analyzed by unpaired t-test.

Results: Both ionotropic antagonists reduced white blood cells with early lymphopenia (P less than 0.05), whereas NBQX also increased Ht and Hb values (P < 0.05), but reduced platelet aggregation (P less than 0.05). T-cell surface activation markers, CD3, CD49a were reduced (P less than 0.05), whereas CD54 was increased (P less than 0.05) 12 h after both antagonists' administration but 24 h after NBQX all markers were increased (P less than 0.05). Bone marrow cells were influenced in a way that peripheral blood changes and segmented cells showed a possible expression of glutamate receptors.

Conclusions: It is concluded that glutamate ionotropic antagonists affect the hematological profile and bone marrow of healthy intact rats as well as blood elements functions. Further research is needed in order to define the in vivo effect of glutamate and glutamate receptor antagonists on hematopoietic system either as a toxic agent or as a therapeutical one.




doi:10.4021/jh101e