title: Toxicity of Arsenic (III) on Isolated Liver Mitochondria: A New Mechanistic Approach.
abstract: Arsenic exposure mainly through food and water has been shown to be associated with increased incidence of numerous cancers and non-cancer harmful health. It is also used in cancer chemotherapy and treatment of several cancer types due to its apoptogenic effects in the various cancer and normal cell lines. We have already reported that liver is the storage site and important target organ in As (III) toxicity and recently, it has been suggested that hepatic toxicity of arsenic could be resulted from impairment of the liver mitochondria. In this study, interaction of As (III) with freshly isolated rat mitochondria was investigated. We determined different mitochondrial toxicity factors as well as mitochondrial sources of ROS formation using specific substrates and inhibitors following addition of As (III) to the mitochondria. Our results showed that arsenic (III) increased mitochondrial ROS formation, lipid peroxidation and mitochondrial membrane potential collapse, cytochrome c release and mitochondrial swelling in a concentration dependent manner. Addition of As (III) in to the isolated mitochondria, inhibited complexes I and II leading to disruption of mitochondrial electron transfer chain, decreased mitochondrial ATP content and ROS formation.
authors.affiliation: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ; Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran. ; Student Research Committee, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mir-Jamal
authors.initials: MJ
authors.lastname: Hosseini
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Shaki
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ghazi-Khansari
authors.forename: Jalal
authors.initials: J
authors.lastname: Pourahmad
keywords: Arsenic (III); Complex I; Complex II; Reactive Oxygen Species; mitochondria