Mitochondria-Targeted Antioxidants: A Step towards Disease Treatment

Table 3

MTAs in TBI models.

Mitochondria-targeted antioxidants/bioactive component	Models/clinical trials	Dosage	Effects/mechanism	Reference
SkQR1	Rat model by brain surgery	100 nmol/kg; intraperitoneal injection	(1) Decreased the neurological deficit; (2) Lowered the volume of the lesion in the brain cortex; (3) Decreased mitochondrial ROS and GSK-3β activity	[106]
	Rat model of focal one-sided TBI	250 nmol/kg; intraperitoneal injection	(1) Rescued the disruptions of limb functions; (2) Increased survivability of neurons; (3) Decreased astroglial expression and infiltration with segmented neutrophils; (4) Beneficial effects are dependent on the reduction of mitochondrial reactive oxygen species	[107]
XJB-5-131	Rat CCI model after TBI	10 mg/kg bodyweight; intravenous injection	(1) Protected brain thiols, GSH and PSH, oxidized by TBI; (2) Decreased caspase 3/7 activity and attenuated apoptotic neuronal death; (3) Scavenged the electrons leaking from electron carriers	[108]
Mito-TEMPO	Isolated MCAs from rats with traumatic injury	30 nmol in the vessel chamber	(1) Alleviated myogenic constriction; (2) Scavenged H2O2 (PEG-catalase) by blocking both BKCa channels and TRPV4 channels	[109]
SS-31	Marmarou’s weight drop model of TBI	5 mg/kg; intraperitoneal administration	(1) Rescued mitochondrial dysfunction, and alleviated secondary brain injury; (2) Decreased ROS, malondialdehyde, and cytochrome c release and prevented the decline of SOD activity; (3) Attenuated neurological deficits, brain water content, DNA damage, and neural apoptosis	[77]
MitoQ	Marmarou’s weight drop model	4 mg/kg; intraperitoneal administration	(1) Alleviated neurological deficits and brain edema and inhibited cortical neuronal apoptosis; (2) Increased the activity of SOD and GPx and decreased MDA level; (3) Reduced Bax translocation to mitochondria and cytochrome c release into the cytosol; (4) Accelerated the Nrf2 nuclear translocation and upregulated the Nrf2 downstream proteins, including HO-1 and Nqo1	[110]

Notes: Bax: (Bcl-2)-associated X; BKCa: big conductance Ca²⁺-activated K⁺; CCI: chronic constriction injury; GPx: glutathione peroxidase; GSH: glutathione; GSK-3β: glycogen synthase kinase-3β; HO-1: heme oxygenase-1; MCAs: middle cerebral arteries; MDA: malondialdehyde; Nqo1: quinone oxidoreductase 1; Nrf2: nuclear factor erythroid 2; PEG-catalase: polyethylene glycol; PSH: protein thiols; SOD: superoxide dismutase; TBI: traumatic brain injury.