title: Toxicity of Atorvastatin on Pancreas Mitochondria: A Justification for Increased Risk of Diabetes Mellitus.
abstract: Statins (including atorvastatin) are a widely used class of drugs, and like all medications, they have a potential for adverse effects. Recently, it has been shown that statins also exert side effects on the pancreas. In vitro studies have suggested that this class of drugs induced a reduction in insulin secretion. Also, the use of statins is associated with a raised risk of diabetes mellitus (DM), but the mechanisms underlying statin-induced diabetes are poorly known. Literature data indicate that several statins are able to induce apoptosis signalling. This study was designed to examine the mechanism of atorvastatin on mitochondria obtained from rat pancreas. In our study, mitochondria were obtained from the pancreas and then exposed to atorvastatin and vehicle to investigate probable toxic effects. The results showed that atorvastatin (25, 50, 75, 100 and 125 μM) increased reactive oxygen species (ROS) production, mitochondrial swelling, collapse of mitochondrial membrane potential and cytochrome c release, the orchestrating factor for mitochondria-mediated apoptosis signalling. Atorvastatin also reduced the ATP levels. These results propose that the toxicity of atorvastatin on pancreas mitochondria is a key point for drug-induced apoptotic cell loss in the pancreas and therefore a justification for increased risk of DM.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Melina
authors.initials: M
authors.lastname: Sadighara
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Amirsheardost
authors.affiliation: Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Minaiyan
authors.affiliation: Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Valiollah
authors.initials: V
authors.lastname: Hajhashemi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Naserzadeh
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Salimi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Department of Occupational Health Engineering, Research Center for Health, Safety and Environment (RCHSE), Alborz University of Medical Sciences, Karaj, Iran.
authors.forename: Enayatollah
authors.initials: E
authors.lastname: Seydi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Jalal
authors.initials: J
authors.lastname: Pourahmad
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin / Q000633:toxicity*; D045304:Cytochromes c / Q000378:metabolism; D003920:Diabetes Mellitus / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000633:toxicity*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008933:Mitochondrial Swelling / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D000069059:Atorvastatin