Increasing attention is being paid to the possibility of applying chemopreventive agents for the protection of individuals from cancer risk. The beneficial potential of chemoprotective compounds is usually well documented by extensive experimental data. To assure the desired effect, these compounds are frequently concentrated to produce dietary supplements for human use. The additive and synergistic effects of other food constituents are, however, frequently ignored. Even natural chemopreventive compounds have to be considered as xenobiotics. Thus, as much attention has to be paid to their testing prior to their wide application as is usual in drug development for human treatment. Unfortunately, much of the research in this area is solely based on simplified in vitro systems that cannot take into account the complexity of biotransformation processes, e.g. chemopreventive compound-drug interaction, effect on metabolism of endogenic compounds. Hence, the predicted chemopreventive potential is not attained in respect of cancer prevention; moreover, the administration of high doses of chemopreventive compounds might be even detrimental for the human health.
- MeSH
- antikarcinogenní látky terapeutické užití MeSH
- financování organizované MeSH
- lidé MeSH
- nádory farmakoterapie patofyziologie prevence a kontrola MeSH
- rizikové faktory MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- xenobiotika metabolismus terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- chemoprofylaxe metody trendy využití MeSH
- experimenty na zvířatech MeSH
- financování organizované MeSH
- flavonoidy aplikace a dávkování diagnostické užití škodlivé účinky MeSH
- játra účinky léků MeSH
- karcinogeny farmakologie MeSH
- potkani Wistar MeSH
- systém (enzymů) cytochromů P-450 metabolismus účinky léků MeSH
- tenké střevo účinky léků MeSH
- western blotting metody využití MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- abstrakty MeSH
Acyclic nucleoside phosphonates are potent antiviral agents effective against replication of DNA viruses and retroviruses including human immunodeficiency virus (HIV). In addition to their antimetabolic mode of antiviral action, acyclic nucleoside phosphonates also possess immunomodulatory properties. We have shown recently that a number of them stimulate secretion of cytokines including chemokines RANTES/CCL5 ("regulated upon activation, normal T cell expressed and secreted") and MIP-1 alpha/CCL3 (macrophage inflammatory protein-1 alpha) that may inhibit entry of HIV in cells. In present experiments we analyzed effects of acyclic nucleoside phosphonates on gene expression of other members of the beta family of chemokines, monocyte chemotactic proteins (MCPs), which have also been implicated in the control of HIV infection. The following compounds differing at the type of heterocyclic base, i.e. adenine (A), or 2,6-diaminopurine (DAP), at the 6-amino group of the base, and at the N ( 9 )-side chain represented by 9-[2-(phosphonomethoxy)ethyl] (PME) and 9-[2-(phosphonomethoxy)propyl] (PMP) moieties were included in the study: (1) (R)-PMPA, ie. tenofovir, (2) N ( 6 )-cyclopropyl-(R)-PMPDAP, (3) N ( 6 )-cyclopentyl-(R)-PMPDAP, (4) N ( 6 )-dimethylaminoethyl-(R)-PMPDAP, (5) N ( 6 )-cyclopentyl-PMEDAP, (6) N ( 6 )-isobutyl-PMEDAP, (7) N ( 6 ) -cyclohexylmetyl-PMEDAP, and (8) N ( 6 ) -cyclooctyl-PMEDAP. These compounds are able to activate production of MCP-1 and MCP-3, and none of them influences gene expression of MCP-2, and MCP-5. Enhancement of monocyte chemotactic protein expression was found to be mediated by transcriptional factor nuclear factor-kappaB (NF-kappaB).
- MeSH
- chemokin CCL2 biosyntéza imunologie MeSH
- HIV infekce farmakoterapie imunologie metabolismus MeSH
- HIV imunologie metabolismus MeSH
- karboxypeptidasy A biosyntéza imunologie MeSH
- kultivované buňky MeSH
- látky proti HIV farmakologie MeSH
- lidé MeSH
- myši MeSH
- nukleosidy farmakologie MeSH
- peritoneální makrofágy imunologie metabolismus MeSH
- replikace viru účinky léků účinky záření MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
