Owiredu 2020 Am J Physiol Cell Physiol
|Owiredu S, Ranganathan A, Eckmann DM, Shofer FS, Hardy K, Lambert DS, Kelly M, Jang DH (2020) Ex vivo use of cell-permeable succinate prodrug attenuates mitochondrial dysfunction in blood cells obtained from carbon monoxide poisoned individuals. Am J Physiol Cell Physiol 319:C129-35.|
Abstract: The purpose of this study was to evaluate a new pharmacological strategy using a first generation succinate prodrug, NV118, in peripheral blood mononuclear cells (PBMCs) obtained from subjects with carbon monoxide (CO) poisoning and healthy controls. We obtained human blood cells from subjects with CO poisoning and healthy control subjects. Intact PBMCs from subjects in the CO and Control group were analyzed with high-resolution respirometry measured in pmol O2 × s-1 × 10-6 PBMCs. In addition to obtaining baseline respiration, NV118 (250 mM) was injected and the same parameters of respiration were obtained for comparison in PBMCs. We measured mitochondrial dynamics with microscopy with the same conditions.
We enrolled 37 patients (17 in the CO group and 20 in the Control group for comparison) in the study. PMBCs obtained from subjects in the CO group had overall significantly lower respiration compared to the Control group (P < 0.0001). There was a significant increase in respiration with NV118, specifically with an increase in maximum respiration and respiration from Complex II and Complex IV (P < 0.0001). The mitochondria in PBMCs demonstrated an overall increase in net movement when compared to the Control group.
Our results of this study suggest that the therapeutic compound, NV118, increases respiration at Complex II and IV as well as restoration of mitochondrial movement in PBMCs obtained from subjects with CO poisoning. Mitochondrial-directed therapy offers a potential future strategy with further exploration in vivo.
Labels: MiParea: Respiration, mt-Structure;fission;fusion, Patients, Pharmacology;toxicology Pathology: Other
Organism: Human Tissue;cell: Blood cells Preparation: Permeabilized cells, Intact cells
Coupling state: LEAK, ROUTINE, ET Pathway: S, CIV, ROX HRR: Oxygraph-2k