MitoVitE, a mitochondria-targeted antioxidant, limits paclitaxel-induced oxidative stress and mitochondrial damage in vitro, and paclitaxel-induced mechanical.

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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 B. McCormick, D.A. Lowes, L. Colvin, C. Torsney, H.F. Galley British Journal of Anaesthesia Volume 117, Issue 5, Pages 659-666 (November 2016) DOI: 10.1093/bja/aew309 Copyright © 2016 The Author(s) Terms and Conditions

Fig 1 Effect of a range of concentrations of paclitaxel plus 1 µM MitoVitE or Trolox, or vehicle control on (A) mitochondrial membrane potential, (B) mitochondrial metabolic activity and (C) glutathione (GSH) in dorsal root ganglion cells. Results are presented as percentage of data at baseline (i.e. vehicle control treated cells without paclitaxel but with antioxidant treatment), to facilitate comparisons between treatments. Data are shown as box and whisker plots showing median, interquartile and full range (n = 6). P value is Kruskal Wallis. * = significantly different to without paclitaxel. British Journal of Anaesthesia 2016 117, 659-666DOI: (10.1093/bja/aew309) Copyright © 2016 The Author(s) Terms and Conditions

Fig 2 Effect of a range of concentrations of paclitaxel plus 1 µM MitoVitE or Trolox, or vehicle control on cell viability in (A) the A2780 ovarian carcinoma cell line and (B) in the MCF-7 breast adenocarcinoma-like oestrogen-sensitive cell line. Results are presented as percentage of data at baseline (i.e. vehicle control treated cells without paclitaxel but with antioxidant treatment), to facilitate comparisons between treatments. Data are shown as box and whisker plots showing median, interquartile and full range (n = 6). P value is Kruskal Wallis. * = significantly different to without paclitaxel. British Journal of Anaesthesia 2016 117, 659-666DOI: (10.1093/bja/aew309) Copyright © 2016 The Author(s) Terms and Conditions

Fig 3 Mechanical hind paw withdrawal thresholds of groups receiving Cremophor (black), paclitaxel with vehicle control (red), paclitaxel with duloxetine (green) and paclitaxel with MitoVitE (blue). Mechanical withdrawal thresholds measured at (A) three h (B) six h and (C) nine h after drug or vehicle administration. Data are shown as mean (SD), n = 5–9 per treatment group. Two-Way ANOVA followed by Bonferroni post hoc test used to compare all groups to paclitaxel with vehicle control. o = Cremophor P<0.001, * = paclitaxel with MitoVitE P<0.05, + = paclitaxel with duloxetine P<0.05. British Journal of Anaesthesia 2016 117, 659-666DOI: (10.1093/bja/aew309) Copyright © 2016 The Author(s) Terms and Conditions

Fig 4 (A) Area under the curve values of mechanical withdrawal thresholds at three, six and nine h after drug/vehicle administration as displayed in Fig 3. Data are shown as mean (SD), n = 5-9 per treatment group. Two-way repeated measures ANOVA with Bonferroni-corrected post hoc tests indicated time-dependent effects of both MitoVitE and duloxetine administration. (B) Mechanical withdrawal thresholds in the 24 h after the last drug/vehicle administration (day 14). Cremophor (black), paclitaxel with vehicle control (red), paclitaxel with duloxetine (green) and paclitaxel with MitoVitE (blue). Two-Way ANOVA followed by Bonferroni post hoc test used to compare all groups to paclitaxel with vehicle control. o = Cremophor P<0.001, * = paclitaxel with MitoVitE P<0.05, + = paclitaxel with duloxetine P<0.05. British Journal of Anaesthesia 2016 117, 659-666DOI: (10.1093/bja/aew309) Copyright © 2016 The Author(s) Terms and Conditions