title: Coenzyme Q10 remarkably improves the bio-energetic function of rat liver mitochondria treated with statins.
abstract: CoQ10 shares a biosynthetic pathway with cholesterol therefore it can be a potential target of the widely available lipid-lowering agents such as statins. Statins are the most widely prescribed cholesterol-lowering drugs with the ability to inhibit HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase. Preclinical and clinical safety data have shown that statins do not cause serious adverse effects in humans. However, their long-term administration is associated with a variety of myopatic complaints. The aim of this study was to investigate whether CoQ10 supplementation of animals under high fat diet (HFD) treated with statins is able to bypass the mitochondrial metabolic defects or not? Animals were divided into 7 groups and fed with either regular (RD) or HFD during experiments. The first group considered as regular control and fed with a RD. Groups 2-7 including HFD control, CoQ10 (10mg/kg), simvastatin (30mg/kg), atorvastatin (30mg/kg), simvastatin+CoQ10 or atorvastatin+CoQ10 treated orally for 30 days and fed with HFD. At the end of treatments, the animals were killed and blood samples were collected for biochemical examinations. The rat liver mitochondria were isolated and several mitochondrial indices including succinate dehydrogenase activity (SDA), ATP levels, mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPP) were determined. We found that triglyceride (Tg), cholesterol (Chol) and low-density lipoprotein (LDL) were augmented with HFD compared to RD and treatment with statins remarkably lowered the Tg, Chol and LDL levels. Mitochondrial parameters including, SDA, ATP levels, MMP and MPP were reduced with statin treatment and improved by co-administration with CoQ10.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Fars 71345-1583, Shiraz, Iran. Electronic address: toxicology@sums.ac.ir.
authors.forename: Afshin
authors.initials: A
authors.lastname: Mohammadi-Bardbori
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Fars 71345-1583, Shiraz, Iran.
authors.forename: Asma
authors.initials: A
authors.lastname: Najibi
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Fars 71345-1583, Shiraz, Iran.
authors.forename: Najmeh
authors.initials: N
authors.lastname: Amirzadegan
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Fars 71345-1583, Shiraz, Iran.
authors.forename: Raziyeh
authors.initials: R
authors.lastname: Gharibi
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Fars 71345-1583, Shiraz, Iran.
authors.forename: Ayat
authors.initials: A
authors.lastname: Dashti
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Fars 71345-1583, Shiraz, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Omidi
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Fars 71345-1583, Shiraz, Iran.
authors.forename: Arastoo
authors.initials: A
authors.lastname: Saeedi
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Fars 71345-1583, Shiraz, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Ghafarian-Bahreman
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Fars 71345-1583, Shiraz, Iran; Pharmaceutical Science Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Niknahad
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001774:Blood Chemical Analysis; D059305:Diet, High-Fat / Q000009:adverse effects; D004357:Drug Synergism; D004734:Energy Metabolism / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D051381:Rats; D017207:Rats, Sprague-Dawley; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D014451:Ubiquinone; D000255:Adenosine Triphosphate; C024989:coenzyme Q10
keywords: Atorvastatin; Coenzyme Q10; HFD (high fat diet); HMG-CoA reductase inhibitors; Mitotoxicity; Simvastatin