title: The Effects of Ascorbate, N-Acetylcysteine, and Resveratrol on Fibroblasts from Patients with Mitochondrial Disorders.
abstract: Reactive oxygen species (ROS) are assumed to be implicated in the pathogenesis of inborn mitochondrial diseases affecting oxidative phosphorylation (OXPHOS). In the current study, we characterized the effects of three small molecules with antioxidant properties (N-acetylcysteine, ascorbate, and resveratrol) on ROS production and several OXPHOS parameters (growth in glucose free medium, ATP production, mitochondrial content and membrane potential (MMP)), in primary fibroblasts derived from seven patients with different molecularly defined and undefined mitochondrial diseases.N-acetylcysteine appeared to be the most beneficial compound, reducing ROS while increasing growth and ATP production in some patients' cells. Ascorbate showed a variable positive or negative effect on ROS, ATP production, and mitochondrial content, while incubation with resveratrol disclosed either no effect or detrimental effect on ATP production and MMP in some cells. The individual responses highlight the importance of investigating multiple parameters in addition to ROS to obtain a more balanced view of the overall effect on OXPHOS when evaluating antioxidant treatment options for mitochondrial diseases.
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research and the Department of Genetic and Metabolic Diseases, Hadassah-Hebrew University Hospital, 91120 Jerusalem, Israel. liza.douiev@mail.huji.ac.il.
authors.forename: Liza
authors.initials: L
authors.lastname: Douiev
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research and the Department of Genetic and Metabolic Diseases, Hadassah-Hebrew University Hospital, 91120 Jerusalem, Israel. devorah228@gmail.com.
authors.forename: Devorah
authors.initials: D
authors.lastname: Soiferman
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research and the Department of Genetic and Metabolic Diseases, Hadassah-Hebrew University Hospital, 91120 Jerusalem, Israel. Korin@hadassah.org.il.
authors.forename: Corinne
authors.initials: C
authors.lastname: Alban
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research and the Department of Genetic and Metabolic Diseases, Hadassah-Hebrew University Hospital, 91120 Jerusalem, Israel. annsr@hadassah.org.il.
authors.forename: Ann
authors.initials: A
authors.lastname: Saada
keywords: ATP; N-acetylcysteine; OXPHOS; ROS; ascorbate; fibroblast; mitochondrial disease; resveratrol