title: Statins lower calcium-induced oxidative stress in isolated mitochondria.
abstract: Statins are widely used cholesterol-lowering agents that exert cholesterol-independent effects including antioxidative. The present study delineates the effects of statins, atorvastatin, and simvastatin on oxidative stress and functions of mitochondria that are the primary cellular sources of oxidative stress. In isolated rat liver mitochondria, both the statins prevented calcium-induced cytochrome c release, lipid peroxidation, and opening of the mitochondrial membrane permeability transition (MPT). Both the statins decreased the activity of mitochondrial nitric oxide synthase (mtNOS), lowered the intramitochondrial ionized calcium, and increased the mitochondrial transmembrane potential. Our findings suggest that statins lower intramitochondrial ionized calcium that decreases mtNOS activity, lowers oxidative stress, prevents MPT opening, and prevents the release of cytochrome c from the mitochondria. These results provide a novel framework for understanding the antioxidative properties of statins and their effects on mitochondrial functions.
authors.affiliation: Department of Biological Sciences, Girls Degree College, Ujjain, Madhya Pradesh, India.
authors.forename: A
authors.initials: A
authors.lastname: Parihar
authors.forename: M S
authors.initials: MS
authors.lastname: Parihar
authors.forename: W J
authors.initials: WJ
authors.lastname: Zenebe
authors.forename: P
authors.initials: P
authors.lastname: Ghafourifar
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011758:Pyrroles; D045304:Cytochromes c; D000069059:Atorvastatin; D019821:Simvastatin; D019001:Nitric Oxide Synthase; D002118:Calcium