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
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.