Fig. 4: HK protects against Doxo-induced senescence and cardiotoxicity.
a, Schematic representation of the experimental design. b, Left, representative images of luciferase detection in untreated and Doxo-injected animals (20 mg kg−1), with or without HK pretreatment (3 days, 0.5 mg kg−1). On the right, histograms show relative luminescence induction as FC (Control n = 4, Doxo n = 3, HK + Doxo n = 5). c, Animal weight loss measured 2 and 4 days after Doxo injection (n = 3). d, Representative images of SA-β-Gal staining of induced cardiomyocytes, with Doxo (SenCMs) or without (iCMs) or with 100 μg ml−1 of HK (n = 5) (left), and its quantification (right). Insets show enlarged image of dashed box. e, mRNA expression of CDKN1A (p21) as determined by RT-qPCR (n = 4). f, HK effect on SenCMs field potentials. Examples of QT interval measured in field potential recorded from different experimental conditions in comparison with baseline (black traces) at day 0 and day 6 are shown in subsets. g, The electrical activity of spontaneously beating iCMs was recorded using MEA for 6 consecutive days at baseline, after Doxo treatment (red line), following exposure of SenCM to HK (Doxo + HK; green line) and after exposure of iCM to HK (UT + HK; gray line) (n = 5 as means of different recordings). Data in b, c, d, e, g are presented as mean ± s.e.m. Statistical test used in b: one-way ANOVA with Holm–Šidák’s multiple comparisons test. Statistical test used in c: two-way ANOVA with Dunnettʼs multiple comparisons test. Statistical test performed in d and e: repeated measures one-way ANOVA with Tukey’s multiple comparisons test. Statistical test performed in g: two-tailed unpaired t-test analyses of Doxo versus Doxo + HK. *P < 0.05; **P < 0.01. Exact P values found in source data files.
