MitoVitE, a mitochondria-targeted antioxidant, limits paclitaxel-induced oxidative stress and mitochondrial damage in vitro, and paclitaxel-induced mechanical hypersensitivity in a rat pain model

Abstract

Paclitaxel affected mitochondrial function and glutathione in DRG cells, which was abrogated by MitoVitE but not Trolox, without decreasing cancer cell cytotoxicity. In rats, paclitaxel-induced mechanical hypersensitivity was ameliorated by MitoVitE treatment to an extent similar to duloxetine. These data confirm mitochondria as a mechanistic target for paclitaxel-induced damage and suggest mitochondria targeted antioxidants as future therapeutic strategies.

β‐Cryptoxanthin exerts greater cardioprotective effects on cardiac ischemia‐reperfusion injury than astaxanthin by attenuating mitochondrial dysfunction in mice

“…Astaxanthin and vitamin E have shown antioxidant effects in cardiac tissues and exerted beneficial effects on mitochondrial homeostasis ; however, the antioxidant effects of β‐cryptoxanthin have never been investigated. The present study found that these antioxidants decreased plasma and cardiac TBARS levels in treated mice compared to control mice.…”

Beyond symptomatic relief for chemotherapy‐induced peripheral neuropathy: Targeting the source

“…65,66 Mitochondria-targeted antioxidants, such as mitoVitE and melatonin, also attenuated paclitaxel-induced neuropathic pain. 67,68 However, despite positive results from preclinical studies, results from clinical studies are less satisfying. Clinical trials using nutraceuticals with antioxidant properties, including vitamin E, acetyl-L-carnitine, glutamine, glutathione, vitamin B6, omega-3 fatty acids, and a-lipoic acid, have reported controversial results.…”

“…Preclinical data have demonstrated great promise for compounds targeting this pathway, such as pifithrin-l, HDAC6 inhibitors, and metformin, as well as antioxidants and peroxynitrite decomposition catalysts as prophylactic treatment of CIPN. 24,27,30,47,[61][62][63][64][65][66][67][68]110 It is interesting to note that HDAC6 inhibitors were found to be effective in both preventing and reversing CIPN, 30 with reported synergistic effects on tumor killing in combination with chemotherapy. 41,42 Given these unique features, HDAC6 inhibition may be a preferred treatment option for patients already receiving chemotherapy.…”

“…The free radical scavenger phenyl N‐tert‐butylnitrone and the superoxide dismutase mimetic TEMPOL ameliorated mechanical allodynia in rats treated with paclitaxel . Mitochondria‐targeted antioxidants, such as mitoVitE and melatonin, also attenuated paclitaxel‐induced neuropathic pain . However, despite positive results from preclinical studies, results from clinical studies are less satisfying.…”

Ultrastructural Changes in the Retina during the Process of Paclitaxel-Induced Retinotoxicity Correction using Antioxidant Drug

“…Ці процеси відбуваються на тлі оки-слювальних ушкоджень, тісно пов'язаних із мітохо-ндріальною дисфункцією клітин [14,7,12,6]. Зроб-лено висновок про можливий напрямок лікування чи корекції таких станів антиоксидантами, але на доказ цього проведена обмежена кількість дослі-джень із вивченням нейропротекторної дії антиок-сидантів [2,13,11].…”