Dexrazoxane does not mitigate early vascular toxicity induced by doxorubicin in mice

Fig 1. Evaluation of vascular reactivity, following short-term in vivo DOX and DEXRA treatment. DOX impaired ACh-induced vasodilation, irrespective of DEXRA pre-treatment (A). DEANO-induced vasodilation did not differ between the treatment groups (A). In both the absence and presence of L-NAME, PE-induced contraction remained unaffected (B). For A: Repeated measures two-way ANOVA with Dunnett’s multiple comparisons test. For B: One-way ANOVA with Dunnett’s multiple comparisons test per L-NAME condition. n = 7 in each group. For A: *p<0.05 for vehicle vs. DOX group; #p<0.05 for vehicle vs. DOX with DEXRA group. For B: p>0.05 for vehicle vs. DOX group and vehicle vs. DOX with DEXRA group.

Fig 2. Evaluation of vascular reactivity, following short-term ex vivo DOX and DEXRA incubation. ACh-induced vasodilation was diminished in the DOX and DOX with DEXRA groups (A). DEANO-induced vasodilation was similar between the treatment groups (A). PE-induced contraction with and without L-NAME was lower following DOX exposure (B). For A: Repeated measures two-way ANOVA with Dunnett’s multiple comparisons test. For B: One-way ANOVA with Dunnett’s multiple comparisons test per L-NAME condition. n = 7 in each group. For A: *, **p<0.05, 0.01 for vehicle vs. DOX group; #, ##p<0.05, 0.01 for vehicle vs. DOX with DEXRA group. For B: *,**p<0.05, 0.01 compared to vehicle.

Fig 3. Evaluation of vascular reactivity, following short-term ex vivo DOX and NAC incubation. DOX diminished ACh-induced vasodilation, irrespective of NAC (A). DEANO-induced vasodilation did not differ between the treatment groups (A). In both the absence and presence of L-NAME, PE-induced contraction was lower in the DOX group, regardless of NAC (B). For A: Repeated measures two-way ANOVA with Dunnett’s multiple comparisons test. For B: One-way ANOVA with Dunnett’s multiple comparisons test per L-NAME condition. n = 8 in vehicle and DOX groups; n = 7 in DOX with NAC group. For A: *p<0.05 for vehicle vs. DOX group; #p<0.05 for vehicle vs. DOX with NAC group; £ 0.05<p<0.08 for vehicle vs. DOX groups and for vehicle vs. DOX with NAC groups. For B: *, ****p<0.05, 0.0001 compared to vehicle.

Fig 4. Assessment of TOP-IIβ expression in the murine thoracic aorta (TA) and heart, following short-term in vivo DOX treatment. RT-qPCR (A) and WB (B) show that murine aortic tissue expresses TOP-IIβ. DOX does not alter TOP-IIβ expression in the heart and aorta (A). DOX decreased TOP-IIβ protein levels in cardiac, but not aortic, tissue (B). Representative blots for panel B (C). For A & B: Mann-Whitney U test. n = 6 in each group. p>0.05 for vehicle vs. DOX groups in panel A. *p<0.05 for vehicle vs. DOX groups in panel B. For C: “L”, “V” and “D” stand for ladder, vehicle and DOX, respectively.