Nitrergic Response TO Cyclophosphamide Treatment in Blood and Bone Marrow



G.A Kevorkian*, N.Kh Alchujyan, N.H Movsesyan, H.L Hayrapetyan, A.G Guevorkian, R.M Ohanyan , S.S Dagbashyan


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© Kevorkian et al.; Licensee Bentham Open

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to these authors at the H. Buniatian Institute of Biochemistry NAS RA, 5/1 P.Sevak St., 0014, Yerevan, Republic of Armenia; E-mail: kevork_neurochem@mail.ru


Abstract

Daily intraperitoneal injection of cyclophosphamide (CPA) (50 mg∙kg-1 of body weight) for 5 days resulted in reduced levels of marrow and blood cellularity, which was most pronounced in 18 days post-treatment (pt). On day 18 after CPA treatment the enhancedlevels of nitric oxide (NO) precursors and metabolites (L-arginine, L-citrulline, reactive nitrogen species (RNS)) of marrow and blood cells (platelet, neutrophil, lymphocyte and monocyte) resulted from up-regulation of Ca(II)/calmodulin(CaM)-independent “inducible” NO synthase (iNOS), with a lessercontribution of Ca(II)/CaM-dependent “constitutive” cNOS isoforms to systemic NO.Biphasic response to CPA of marrow nitrergic system, i.e. both iNOS and cNOS showed significantly depressed activities, as well as diminished levels of NO metabolites on day 9 pt, suggested that signals in addition to NO might be involved in CPA-induced inhibition of hematopoesis, while a gradual increase of neutrophil and platelet NOS activity appeared to be contributed to a CPA-induced development of granulopenia, thrombocytopenia and hemorrhage.

Key words: Cyclophosphamide, arginine, blood formed elements, citrulline, nitric oxide synthase, marrow, rat.