Protective effect of fluvastatin, an HMG-CoA reductase inhibitor, on the formation of 8-oxo-2'-deoxyguanosine in the nuclear DNA of hamster pancreas after a single administration of N-nitrosobis(2-oxopropyl)amine.
We examined whether fluvastatin (FV), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has antioxidant activity against oxidative DNA damage to hamster pancreas induced by a chemical carcinogen, N-nitrosobis(2-oxopropyl)amine (BOP). Female Syrian golden hamsters were treated with FV by gastric intubation 30 min before BOP administration. Control animals were intubated with saline. Animals were injected subcutaneously with BOP (20 mg/kg body weight) or saline, and sacrificed 1 and 4 h later. The contents of 8-oxo-2'-deoxyguanosine (8-oxodG) in the nuclear DNA and thiobarbituric acid-reacting substances (TBARS) were measured in the pancreas and liver of hamsters. Treatment with more than 0.22 mg/kg body weight FV significantly inhibited the increase in 8-oxodG content induced by BOP treatment. The TBARS contents in pancreas changed similarly by intubation of FV. In the liver, the contents of 8-oxodG and TBARS were not affected by a single administration of BOP. The protective effect of FV was stronger than those of pravastatin and other antioxidants such as Trolox, ascorbic acid and green tea catechin. These results suggest that FV inhibits oxidative damage to DNA and lipids caused by reactive oxygen species formed through the metabolism of chemical carcinogens.
Kaneko
Takao
T
Redox Regulation Research Group, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. kaneko@tmig.or.jp
Tahara
Shoichi
S
Takabayashi
Fumiyo
F
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005260:Female; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D015227:Lipid Peroxidation; D008647:Mesocricetus; D009602:Nitrosamines / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances
D000975:Antioxidants; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D009602:Nitrosamines; D017392:Thiobarbituric Acid Reactive Substances; D000077340:Fluvastatin; C013622:nitrosobis(2-oxopropyl)amine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine