|
| Classification | Compound | Experimental model | Effect |
|
| CypD inhibition independent | Melatonin | Rat stroke model | Decreased neuron loss and reduced infarct volume [124] |
| CypD inhibition dependent | Cyclosporin A (CsA) | Ischemic reperfusion injury rat heart [118]; anoxia-induced injury in rat heart myocytes [139] | Cardioprotection [118]; reduced proportion of necrosis in rat heart myocytes [139] |
| N-Methyl-isoleucine-4-cyclo-sporin (NIM811) | Isolated mitochondria in rat hepatocytes (TNFα-induced permeable transition onset) | Mitochondrial permeability transition onset and apoptosis prevented [114] |
| CypD inhibition independent | (E)-3-(4-Fluoro-3-hydroxy-phenyl)-N-naphthalen-1-yl-acrylamide (compound 22) | Rabbit model of acute myocardial infarction | Cardioprotective; reduced infarct size; inhibitor of mPTP openings [127] |
| Edaravone (Radicut™) | Ischemia/reperfusion injury in rat brain | Neuroprotective; inhibited Ca2+- and H2O2-induced swelling in mitochondria; inhibited Ca2+ generation of ROS [140] |
| N-Phenylbenzamides (CypD inhibition independent) | Compound 4, (3-(benzyloxy)-5-chloro-N-(4-(piperidin-1-ylmethyl)phenyl)benzamide) | Ca2+ retention capacity (CRC) assay in HeLa cells | Induced a concentration-dependent increase in the CRC of permeabilized HeLa cells (indicative of mPTP inhibition) [129] |
| Isoxazoles (CypD inhibition independent) | Compound 1, 5-(3-hydroxyphenyl)-N-(3,4,5-trimethoxyphenyl)isoxazole-3-carboxamide | mPTP openings measured by CRC in isolated mouse liver mitochondria | Inhibitory activity against mitochondrial swelling; no interference on the inner mitochondrial membrane potential [130] |
| Cinnamic anilides (CypD inhibition independent) | GNX-4728 | Mouse model of amyotrophic lateral sclerosis (ALS) | Slowed disease progression and significantly improved motor function; displayed a nearly 2-fold extension of lifespan; established mitochondrial calcium retention [128] |
| Electron scavengers/antioxidants (CypD inhibition independent) | SS-31 | 15-month-old male mice exposed to isoflurane [141]; antioxidant properties of SS peptides in neuronal N2A cells treated with t-butylhydroperoxide (tBHP) [131] | Enhances synaptic plasticity and provides protective effects on cognitive function [141]; reduced intracellular ROS and increased cell survival [131] |
| XJB-5-131 | Cardiolipin oxidation as a byproduct of experimental traumatic brain injury in rats [133]; cardiac function in aged rats [132]; muscle contractility of aged adult rats [142] | Inhibition of cardiolipin oxidation and subsequent improvement in motor skills and cognitive operations [133]; improved postischemic recovery of aged hearts, reduced Ca(2+)-induced swelling in the mitochondria, attenuated the H2O2-induced depolarization of the mitochondrial inner membrane as well as the total and mitochondrial ROS levels in cultured cardiomyocytes [132]; higher muscle contractility [142] |
| MitoQ | Cardiac ischemia-reperfusion injury in rats | Decreased heart dysfunction, cell death, and mitochondrial damage after ischemia-reperfusion [134] |
| EUK-8 | Oxidative stress-sensitized harlequin (Hq) mutant mice and their wild-type (WT) counterparts [143]; presymptomatic heart/muscle-specific manganese-superoxide dismutase- (Mn-SOD-) deficient mice [135] | Improved left ventricular end-systolic dimensions and fractional shortening, prevented myocardial oxidant stress, attenuated necrotic and apoptotic cell death, and attenuated cardiac hypertrophy and fibrosis in both Hq and WT [143]; suppressed the progression of cardiac dysfunction and diminished ROS production and oxidative damage [135] |
| MitoTEMPO | Amyloid-beta toxicity in primary cultured mouse neurons | Neuronal lipid oxidation was significantly suppressed; demonstrated protective effects on mitochondrial bioenergetics evidenced by preserved mitochondrial membrane potential and cytochrome c oxidase activity as well as ATP production [136] |
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