Cell lines

HSC-T6 cells

Preparation Method

Mitoquinone mesylate was added directly to the culture medium at final concentrations of 2 µM, 20 µM, 13 µM, 50 nM, or 10 µM, respectively, for 24 h.

Reaction Conditions

2 µM, 20 µM, 13 µM, 50 nM, or 10 µM for 24 hours

Applications

Confocal fluorescence microscopy showed that mitoquinone mesylate treatment reversed fragmented mitochondria in active HSCs to an elongated state. Immunoblot analysis showed significantly downregulated Fis1 and Drp1 after mitoquinone mesylate treatment.

Animal models

male Wistar rats

Preparation Method

For pharmacokinetic study, groups of rats (n = 4-5) were administered either an intravenous (IV) dose (5 mg/kg) via the cannula or an oral dose (25 mg/kg) by gavage.

Dosage form

Intravenous injection, 5 mg/kg; oral, 25 mg/kg.

Applications

After oral administration, mitoquinone mesylate was rapidly absorbed giving a plasma concentration of about 25 ng/mL after about 1 h. Thereafter, mitoquinone mesylate concentration fluctuated reaching a maximum (Cmax) of 31.2 ± 6.9 ng/mL at 4.0 h. After IV administration, the plasma concentration of mitoquinone mesylate exhibited an exponential decline with a rapid distribution phase followed by a slower elimination phase

• J Agr Food Chem (2022). PMID:36239691

Mitoquinone mesylate (Mitoquinone methanesulfonate) is among the widely used antioxidants that target the mitochondria. It was developed to readily penetrate the BBB and neuronal membranes, where it is concentrated into several hundred-folds within the mitochondria where it mediates the local anti-oxidative capacity^[1]. Within the ETC, complex II, also known as succinate dehydrogenase, reduces Mitoquinone mesylate ubiquinone moiety to the active antioxidant ubiquinol which scavenges excess ROS^[2].

Mitoquinone mesylate (50 nM) reduced 6-OHDA-induced mitochondrial fragmentation, when used in SH-SY5Y cell line. It inhibited mitochondrial fission protein and the translocation of pro-apoptotic protein (Bax) in the mitochondria^[3].

Mitoquinone mesylate treatment inhibited the loss of dopaminergic neurons and enhanced behavioral performance, showed neuroprotective effects in mouse models of PD^[4]. Mitoquinone mesylate treatment enhanced the fine motor control and reduced markers of oxidative damage in muscles in a Huntington's disease (HD) mouse model^[5]. Mitoquinone mesylate reduced white matter injury, improved neurological performance, and decreased motor-evoked potential latency in intracerebral hemorrhagic (ICH) mice^[6].

References:
[1]. Murphy M P, Smith R A J. Targeting antioxidants to mitochondria by conjugation to lipophilic cations[J]. Annu. Rev. Pharmacol. Toxicol., 2007, 47: 629-656.
[2]. James A M, CochemE H M, Smith R A J, et al. Interactions of Mitochondria-targeted and Untargeted Ubiquinones with the Mitochondrial Respiratory Chain and Reactive Oxygen Species: IMPLICATIONS FOR THE USE OF EXOGENOUS UBIQUINONES AS THERAPIES AND EXPERIMENTAL TOOLS*?[J]. Journal of Biological Chemistry, 2005, 280(22): 21295-21312.
[3]. Solesio M E, Prime T A, Logan A, et al. The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson's disease[J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2013, 1832(1): 174-182.
[4]. Pinho B R, Duarte A I, Canas P M, et al. The interplay between redox signalling and proteostasis in neurodegeneration: In vivo effects of a mitochondria-targeted antioxidant in Huntington's disease mice[J]. Free Radical Biology and Medicine, 2020, 146: 372-382.
[5]. Pinho B R, Duarte A I, Canas P M, et al. The interplay between redox signalling and proteostasis in neurodegeneration: In vivo effects of a mitochondria-targeted antioxidant in Huntington's disease mice[J]. Free Radical Biology and Medicine, 2020, 146: 372-382.
[6]. Chen W, Guo C, Jia Z, et al. Inhibition of mitochondrial ROS by MitoQ alleviates white matter injury and improves outcomes after intracerebral haemorrhage in mice[J]. Oxidative medicine and cellular longevity, 2020, 2020.