The Open Biochemistry Journal

ISSN: 1874-091X ― Volume 13, 2019

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


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.

Article Information

Identifiers and Pagination:

Year: 2008
Volume: 2
First Page: 81
Last Page: 90
Publisher Id: TOBIOCJ-2-81
DOI: 10.2174/1874091X00802010081

Article History:

Received Date: 7/4/2008
Revision Received Date: 22/4/2008
Acceptance Date: 13/5/2008
Electronic publication date: 3/6/2008
Collection year: 2008

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* 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:


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