Mitochondrial dysfunction induced by different concentrations of gadolinium ion

Gadolinium-based compounds are the most widely used paramagnetic contrast agents in magnetic resonance imaging on the world. But the tricationic gadolinium ion (Gd3+) could induce cell apoptosis probably because of its effects on mitochondria. Until now, the mechanism about how Gd3+ interacts with mitochondria is not well elucidated. In this work, mitochondrial swelling, collapsed transmembrane potential and decreased membrane fluidity were observed to be important factors for mitochondrial permeability transition pore (mtPTP) opening induced by Gd3+. The protection effect of CsA (Cyclosporin A) could confirm high concentration of Gd3+ (500 μM) would trigger mtPTP opening. Moreover, mitochondrial outer membrane breakdown and volume expansion observed clearly by transmission electron microscopy and the release of Cyt c (Cytochrome c) could explain the mtPTP opening from another aspect. In addition, MBM+ (monobromobimane+) and DTT (dithiothreitol) could protect thiol (-SH) groups from oxidation so that the toxicity of Gd3+ might be resulted from the chelation of -SH of membrane proteins by free Gd3+. Gd3+ could inhibit the initiation of mitochondrial membrane lipid peroxidation, so it might interact with anionic lipids too. These findings will highly contribute to the safe applications of Gd-based agents.