The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients

Abstract

Administration of the mitochondria-targeted anti-oxidant mitoquinone significantly decreased plasma ALT and aspartate aminotransferase in patients with chronic HCV infection, and this suggests that mitoquinone may decrease necroinflammation in the liver in these patients. As mitochondrial oxidative damage contributes to many other chronic liver diseases, such as steatohepatitis, further studies using mitochondria-targeted anti-oxidants in HCV and other liver diseases are warranted.

Oxidative stress modulation in hepatitis C virus infected cells

“…Based on the multiple oxidant and antioxidant activities performed in vivo and in vitro systems during viral infections, and the variable ability of antioxidants to cross cell membranes, the systematic use of antioxidants as antiviral therapies had been limited [40] . On the other hand, HCV is potentially lymphotropic, because it can invade and propagate in cells of the [47,48] 400-544 IU/d or 600 mg 1 Vitamin C [48] 500 mg-10 g N-acetylcysteine [78] 600 mg or 1800 mg/d 1 Mitoquine Q [65,66] 40 or 80 mg/d α-tocopherol [79] 600 mg, 500 mg/d, 800 IU/d Glycyrrhizin [40,42,53,54] 500 mg, 120 mg Different mechanisms Silymarin (Silibinin A, Silibinin B, etc.) [40,64,[80][81][82] 250 mg or 5-20 mg/kg 1 S-adenosylmethionine [69] 1600 mg/d 1 Acetylsalicylic acid [73] 4 mmol/L (in vitro) Gallic acid 300 mg/mL (in vitro) 1 Combined treatment with interferon.…”

Selective Mitochondrial Targeting Exerts Anxiolytic Effects In Vivo

“…The fact that the anxiolytic effect was only present in HAB mice and not in other mouse strains which are not inbred for high anxiety, underlines a specificity that could be of use for translational applications in patients with anxiety disorders. Importantly, long-term treatment with MitoQ is also welltolerated in human cohorts and was administered in clinical trials for Parkinson's disease (Snow et al, 2010) and chronic hepatitis C (Gane et al, 2010) with no adverse side effects.…”

Protection Against Oxidative Stress and “IGF-I Deficiency Conditions”

“…Importantly, the first clinical evidence of a potential benefit of MitoQ10 in humans comes from a study that MitoQ10 reduces liver damage induced by hepatitis virus infection [107].…”

“…SS-Peptides the Szeto-Schiller (SS) compounds are tetrapeptides with an alternating aromaticcationic amino acids motif, and demonstrated in the inner mitochondrial membrane more than 1000-fold in comparison with the cytosolic concentration [108][109][110]. Although the positive charge might explain the mitochondrial-targing effect, the mitochondrial uptake of these SS peptides appears to be on mitochondrial potencial, as they are concentrated even in depolarized mitochondria [91,92].…”