The Effect of Ethoxyquin on Mitochondrial Function in Human Fibroblasts

Author(s): Adi Levy, Madleen Zighan, Ahmet Höke, Chaya Miller, Liza Douiev, Patrick Yu-Wai-Man, David Arkadir and Ann Saada

Ethoxyquin (EQ) is a synthetic antioxidant historically used as a preservative in animal feed, but was recently banned as a feed ingredient in food-producing animals due to human health concerns. Nevertheless, EQ was reported to have a neuroprotective effect, ameliorating the side effects of anti-cancer chemotherapy and increasing ATP content in animal models. As the effect of EQ has not been investigated in humans, we aimed to examine its effect of primary fibroblasts derived from controls and patients with confirmed mitochondrial dysfunction. To this end, we incubated primary fibroblasts from patients with mitochondrial respiratory chain complex 1 (C1) deficiency, cytochrome-c-oxidase (COX) deficiency, and a genetic form of Parkinson’s disease (PD). Although EQ did not alter ATP production, it significantly increased oxygen consumption and improved energy status in C1 and COX cells, decreased ROS production in COX, PD, and control cells, while maintaining or increasing mitochondrial content. Our results indicate that EQ has the potential to improve some mitochondrial functions in patients’ cells without any apparent negative effects. Nevertheless, as EQ is controversial and clinical studies are lacking, the use of this compound and its derivatives remains uncertain.