title: Impaired mitochondrial function and oxidative stress in rat cortical neurons: implications for gadolinium-induced neurotoxicity.
abstract: Gadolinium (Gd), a rare-earth lanthanides metal, is widely utilized for various industrial and medical purposes, particularly in brain magnetic resonance imaging. However, its potential effects on the impairment of the central nervous system remain uncertain, especially with regard to the mitochondria, the potential primary target in metal-induced neural injury. This study investigates the effects of gadolinium on mitochondrial energy metabolism, ROS accumulation, and cell death toward cortical neurons. Results show that the metabolic activity of the mitochondria significantly decreased as early as 3h after exposure of cells to gadolinium chloride. Subsequently, significant elevation of intracellular ROS, decrease in ATP synthesis, depolarization of mitochondrial membrane potential, release of cytochrome c and activation of caspase-3 were observed. Following these changes, increased release of LDH into culture medium and DNA fragmentation were detected. Inhibition of both cytochrome c release and caspase-3 activation could significantly reduce Gd-induced neuron cell death. All these results suggest that gadolinium cause neuron cell apoptosis primarily by inhibiting mitochondrial function and inducing oxidative stress. The present work provides new insight into the toxicological mechanism of gadolinium in neurons.
authors.affiliation: State Key Laboratory of Natural and Biomimietic Drugs and Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Feng
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
authors.forename: Lan
authors.initials: L
authors.lastname: Yuan
authors.forename: Xiaoda
authors.initials: X
authors.lastname: Yang
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D018929:Cell Culture Techniques; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D045304:Cytochromes c / Q000037:antagonists & inhibitors / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005682:Gadolinium / Q000037:antagonists & inhibitors / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D061945:Caspase Inhibitors; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D005682:Gadolinium; D053148:Caspase 3