IN-VITRO INHIBITION OF HUMAN CYTOMEGALOVIRUS REPLICATION BY DESFERRIOXAMINE

被引:37
作者
CINATL, J
CINATL, J
RABENAU, H
GUMBEL, HO
KORNHUBER, B
DOERR, HW
机构
[1] UNIV FRANKFURT,CTR PEDIAT,DEPT HEMATOL & ONCOL,D-60596 FRANKFURT,GERMANY
[2] UNIV FRANKFURT,CTR OPHTHALMOL,D-60596 FRANKFURT,GERMANY
关键词
HUMAN CYTOMEGALOVIRUS; DESFERRIOXAMINE; RIBONUCLEOTIDE REDUCTASE; IRON;
D O I
10.1016/0166-3542(94)90095-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Desferrioxamine (DFO) is commonly used in therapy as a chelator of ferric ion in disorders of iron overload. We found that DFO inhibits human cytomegalovirus (HCMV) replication in infected cultures of human foreskin fibroblasts (HFF) at concentrations that have been achieved in humans with no significant adverse effects. The concentrations of DFO required for 50 and 90% reduction in the production of a HCMV-late antigen ranged for several HCMV strains from 3.1 to 4.9 mu M and from 14.2 to 17.3 mu M, respectively. DFO concentration of 60 mu M had no significant effect on the viability of HFF cells. Inhibitory effects of DFO on HCMV replication were completely prevented by co-incubation with stoichiometric amounts of Fe3+.
引用
收藏
页码:73 / 77
页数:5
相关论文
共 21 条
[1]   PHARMACOKINETICS AND RENAL ELIMINATION OF DESFERRIOXAMINE AND FERRIOXAMINE IN HEALTHY-SUBJECTS AND PATIENTS WITH HEMOCHROMATOSIS [J].
ALLAIN, P ;
MAURAS, Y ;
CHALEIL, D ;
SIMON, P ;
ANG, KS ;
CAM, G ;
LEMIGNON, L ;
SIMON, M .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1987, 24 (02) :207-212
[2]   RIBONUCLEOTIDE REDUCTASE OF HERPES-SIMPLEX VIRUS TYPE-2 RESEMBLES THAT OF HERPES-SIMPLEX VIRUS TYPE-1 [J].
AVERETT, DR ;
FURMAN, PA ;
SPECTOR, T .
JOURNAL OF VIROLOGY, 1984, 52 (03) :981-983
[3]  
AVERETT DR, 1983, J BIOL CHEM, V258, P9831
[4]   IMPAIRMENT OF NUCLEOTIDE-METABOLISM BY IRON-CHELATING DEFEROXAMINE [J].
BARANKIEWICZ, J ;
COHEN, A .
BIOCHEMICAL PHARMACOLOGY, 1987, 36 (14) :2343-2347
[5]   METABOLIC-ACTIVATION OF THE NUCLEOSIDE ANALOG 9-([2-HYDROXY-L-(HYDROXYMETHYL)ETHOXY]METHYL)GUANINE IN HUMAN-DIPLOID FIBROBLASTS INFECTED WITH HUMAN CYTOMEGALO-VIRUS [J].
BIRON, KK ;
STANAT, SC ;
SORRELL, JB ;
FYFE, JA ;
KELLER, PM ;
LAMBE, CU ;
NELSON, DJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (08) :2473-2477
[6]  
CINATL J, 1992, ARZNEIMITTEL-FORSCH, V42-2, P977
[7]  
DONFRANCESCO A, 1990, CANCER RES, V50, P4929
[9]   MONITORING OF GANCICLOVIR SENSITIVITY OF MULTIPLE HUMAN CYTOMEGALOVIRUS STRAINS COINFECTING BLOOD OF AN AIDS PATIENT BY AN IMMEDIATE-EARLY ANTIGEN PLAQUE-ASSAY [J].
GERNA, G ;
BALDANTI, F ;
ZAVATTONI, M ;
SARASINI, A ;
PERCIVALLE, E ;
REVELLO, MG .
ANTIVIRAL RESEARCH, 1992, 19 (04) :333-345
[10]   NEUTRALIZATION OF EPSTEIN-BARR VIRUS-INDUCED RIBONUCLEOTIDE REDUCTASE WITH ANTIBODY TO THE MAJOR RESTRICTED EARLY ANTIGEN POLYPEPTIDE [J].
GOLDSCHMIDTS, WL ;
GINSBURG, M ;
PEARSON, GR .
VIROLOGY, 1989, 170 (01) :330-333