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

Imaeda, A Aoki, T Kondo, Y Hori, M Ogata, M Obayashi, H Hasegawa, G Nakamura, N Tokuda, K Nishino, H Yoshikawa, T Kondo, M

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

29

INGLESE

Article

Biochemistry & Biophysics

FREE RADICAL RESEARCH

1071-5762 → ACNP

34

1

2001

33 - 44

ISI

1071-5762(2001)34:1<33:PEOFAR>2.0.ZU;2-W

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.