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Wakabayashi, I; Mayer, B; Groschner, K.
Inhibitory effects of aclarubicin on nitric oxide production in aortic smooth muscle cells and macrophages.
Biochem Pharmacol. 2000; 59(6):719-726 Doi: 10.1016/S0006-2952(99)00358-5
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Groschner Klaus
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Abstract:
The effects of aclaruhicin (ACR), an anthracycline antibiotic, on inducible nitric oxide (NO) synthesis was investigated in rat aortic smooth muscle cells (RASMCs) and RAW macrophages. ACR at concentrations as low as 0.1 microM significantly inhibited NO production induced by interleukin-1beta in RASMCs. About 5- to 10-fold higher concentrations of ACR were required for inhibition of interferon-gamma and lipopolipopolysaccharide-induced NO production in RAW cells. When ACR was subsequently administered to inducible NO synthase (iNOS) induction, the NO production was barely suppressed in RASMCs. Moreover, ACR (up to 10 microM) lacked direct inhibitory effects on iNOS activity in homogenates of these cells. ACR (0.1 microM) inhibited the expression of iNOS protein and mRNA in RASMCs without concomitant cytotoxic effects. ACR (>0.5 microM)-induced inhibition of NO production in RAW cells was associated with substantial cytotoxic effects as shown by measurement of lactate dehydrogenase release. These results suggest that ACR is a potent inhibitor of iNOS induction in vascular smooth muscle, but inhibits iNOS induction in macrophage only at high cytotoxic
Find related publications in this database (using NLM MeSH Indexing)
Aclarubicin - pharmacology
Animals -
Antibiotics, Antineoplastic - pharmacology
Aorta - cytology
Cell Division - drug effects
Cells, Cultured -
Dichlororibofuranosylbenzimidazole - pharmacology
Enzyme Inhibitors - pharmacology
Macrophages - drug effects Macrophages - metabolism
Male -
Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - metabolism
Nitric Oxide - metabolism
Nitric Oxide Synthase - biosynthesis Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II -
RNA, Messenger - metabolism
Rats -
Rats, Wistar -

Find related publications in this database (Keywords)
aclarubicin
vascular smooth muscle cell
macrophage
inducible nitric oxide synthase
gene transcription
cytotoxicity
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