Protective effects of fluvastatin against reactive oxygen species induced DNA damage and mutagenesis

Citation
A. Imaeda et al., Protective effects of fluvastatin against reactive oxygen species induced DNA damage and mutagenesis, FREE RAD RE, 34(1), 2001, pp. 33-44
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
FREE RADICAL RESEARCH
ISSN journal
1071-5762 → ACNP
Volume
34
Issue
1
Year of publication
2001
Pages
33 - 44
Database
ISI
SICI code
1071-5762(2001)34:1<33:PEOFAR>2.0.ZU;2-W
Abstract
Oxidative stress may be an important factor in the development of diabetic complications. Advanced glycation end-products have drown attention as pote ntial sources of oxidative stress in diabetes. We investigated the protecti ve effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductas e inhibitor, on oxidative DNA damage from reactive oxygen species or advanc ed glycation end-products in vitro, as well as effects of main fluvastatin metabolites and other inhibitors of the same enzyme, pravastatin and simvas tatin. Protective effects were assessed in terms of the DNA breakage rate i n a single-stranded phage DNA system in vitro. DNA was exposed to either re active oxygen species or advanced glycation end-products. Fluvastatin and i ts metabolites showed a strong protective effect comparable to those seen w ith thiourea and mannitol, though pravastatin and simvastatin did not exert clear protective effects. Furthermore, fluvastatin reduced the mutagenesis by reactive oxygen species or advanced glycation end-products in Salmonell a typhimurium test strains. Both pravastatin and simvastatin still lacked p rotective activity. Fluvastatin and its metabolites protect against oxidati ve DNA damage and may reduce risk of consequent diabetic complications.