Table 3.

Main published preclinical and clinical studies investigating mitochondria-targeting anti-oxidants.

Molecule	Type of Study	Model/Disease	Treatment	Results	Ref
MitoQ	Preclinical study	Animal model of I/R injury	MitoQ (4 mg/kg) was administered to the mice intravenously 15 min prior to ischemia	MitoQ attenuated renal dysfunction through a reduction in oxidative damage	[88,89]
	Clinical studies	To evaluate the efficacy of MitoQ for improving physiological function (vascular, motor, and cognitive) in middle-aged and older adults (≥60 years)	Oral supplementation of MitoQ (20 mg/day for 6 weeks)	MitoQ improved endothelial function, reduced aortic stiffness and decreased plasma oxidized LDL without altering circulating markers of inflammation or traditional cardiovascular disease risk factor	[90]
		Treatment of patients with Parkinson’s Disease	Two doses of MitoQ (40 or 80 mg once daily) for a period of 12 months versus placebo	MitoQ did not slow the progression of Parkinson’s Disease	[91]
		A Phase 2, randomized, double-blind, parallel design trial to evaluate the ability of MitoQ to reduce raised serum alanine transaminase (ALT) seen in patients with chronic Hepatitis C compared with placebo	Two doses of MitoQ (40 or 80 mg once daily) for 28 days	Both treatment groups showed significant decreases in absolute and percentage changes in serum ALT from baseline to treatment day 28	[92]
SS-31 (Elamipretide, Bendavia, MTP-131)	Preclinical study	Animal model of I/R injury	SS-31 (2.0 mg/kg per day) was administered for 6 weeks, starting 1 month after ischemia	SS-31 restored mitochondria structure in endothelial cells, podocytes, and tubular cells with consequent restoration of peritubular and glomerular capillaries, preservation of podocyte architecture, suppression of inflammation, and fibrosis	[93]
		Mice treated with aristolochic acid or adriamycin to induce acute kidney injury	SS-31 (3 mg/kg) was administered intraperitoneally once a day, starting 1 day before the disease-inducing drugs and then daily until day 6	SS-31 modulated the expression of of members of the RAS system	[94]
	Clinical studies	Patients with severe atherosclerotic renal artery stenosis scheduled for percutaneous transluminal renal angioplasty (PTRA)	Patients were treated before and during PTRA with elamipretide (0.05 mg/kg per hour intravenous infusion) or placebo	Adjunctive elamipretide during PTRA was associated with attenuated postprocedural hypoxia, increased renal blood flow, and improved kidney function	[95]
		Phase 2a, randomized, double-blind, placebo-controlled trial enrolling 300 patients with a first-time anterior STEMI and an occluded proximal or mid-left anterior descending artery undergoing primary percutaneous coronary intervention (PCI) that evaluated the efficacy and safety of Bendavia	Patients were randomized to receive either Bendavia at 0.05 mg/kg per hour or a placebo	Treatment with MTP-131 was not associated with a decrease in myocardial infarct size	[96]
		Double-blind, placebo-controlled trial to evaluate safety, tolerability, and pharmacokinetics of escalating single intravenous infusion doses of Bendavia (MTP-131)	Patients with heart failure with reduced ejection fraction (ejection fraction, ≤35%) were randomized to either a single 4-h infusion of elamipretide (cohort 1, 0.005; cohort 2, 0.05; and cohort 3, 0.25 mg·kg−1·h−1) or placebo	A single infusion of elamipretide was safe and well-tolerated. High-dose elamipretide resulted in favorable changes in left ventricular volumes that correlated with peak plasma concentrations, supporting a temporal association and dose-effect relationship	[97]
		Elamipretide in adults with primary mitochondrial myopathy	Participants were randomly assigned (1:1) to 40 mg/day subcutaneous elamipretide for 4 weeks followed by placebo subcutaneous for 4 weeks, separated by a 4-week washout period, or the opposite sequence	Elamipretide was generally well-tolerated and participants who received short-course daily elamipretide for 4 weeks had clinically meaningful improvements in 6 min walk test	[98]
		Randomized, double-blind, placebo-controlled crossover trial followed by an open-label extension to test the effect of elamipretide in Barth syndrome (BTHS)	A group of patients (12 subjects) was randomized to receive 40 mg per day of elamipretide or placebo for 12 weeks, followed by a 4-week washout and then 12 weeks on the opposite arm. Ten subjects continued on the open-label extension (part 2) of 40 mg per day of elamipretide, with 8 subjects reaching 36 weeks	At 36 weeks in part 2, there were significant improvements in 6 min walk test and BTHS Symptom Assessment (BTHS-SA) scale	[99]
Tempol	Pre-clinical study	Animal model of I/R injury	Tempol (30 mg/kg intravenously) prior to and throughout reperfusion	Tempol attenuated renal dysfunction at least partially through reduced renal activity of MPO and level of MDA	[100]
Mito-TEMPO	Pre-clinical study	Animal model of I/R injury	25 μL Mito-tempo was directly injected into each kidney of the mice after reperfusion followed by daily intraperitoneal injection of mito-TEMPO (5 mg/kg) until day 5	Mito-TEMPO restored the renal mtDNA level, mitochondrial mass, and ATP production with consequent reduced inflammation and kidney injury	[101]
XJB-5-131	Pre-clinical study	Animal model of I/R injury	The mice were injected intraperitoneally with XJB-5-131 (10 mg/kg) 30 min prior to ischemia and for 3 consecutive days after surgery	XJB-5-131 attenuated I/R-induced renal injury and inflammation in mice by specifically inhibiting ferroptosis	[102]