In vitro anti-oxidant and DNA protective effects of the novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor rosuvastatin.
1. Free radical-induced lipid peroxidation and changes in protein and nucleic acid structures can result in various human ailments, including ageing, neurodegenerative disorders and cancer. High body fat or dietary fat further enhances the free radical-mediated pathogenesis of various diseases. 2. In the present study, the in vitro anti-oxidant and DNA protective effects of the novel cardiovascular drug rosuvastatin were evaluated. Anti-oxidant activity was evaluated on the basis of inhibition of lipid peroxidation, scavenging of superoxide radical and the reduction of ferric ions (Fe(3+)). Inhibition of lipid peroxidation was determined using Fenton's reaction-induced lipid peroxidation in rat liver and brain homogenates and liver mitochondria. Superoxide radical-scavenging activity was evaluated by scavenging of the superoxide anion generated by photo illumination of riboflavin and Fe(3+)-reducing activity was determined by the ferric-reducing anti-oxidant power (FRAP) assay. DNA protection was evaluated according to changes in H(2)O(2)-induced pBR322 plasmid DNA and Fenton's reaction-induced-fragmentation of rat liver DNA. 3. The results indicate that rosuvastatin (1.5 or 2 mg/mL) is able to protect against lipid peroxidation. Furthermore, H(2)O(2)-induced changes in pBR322 plasmid DNA and fragmentation of hepatic DNA were alleviated by rosuvastatin. However, rosuvastatin did not show any superoxide anion-scavenging activity. The protective mechanism of rosuvastatin can be correlated with the reducing equivalent donating property or direct hydroxyl radical-scavenging activity of the drug. 4. The pleiotropic activities of rosuvastatin exhibited suggest its clinical advantages against oxidative stress-induced human ailments in addition to its widely using hypolipidaemic effect.
Ajith
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TA
Department of Biochemistry, Amala Institute of Medical Sciences, Amala Nagar, Thrissur, Kerala, India. taajith@rediffmail.com
Riji
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Anu
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005464:Fluorobenzenes / Q000494:pharmacology*; D006861:Hydrogen Peroxide; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*
D000975:Antioxidants; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D006861:Hydrogen Peroxide