Doxorubicin Dose-Dependent Impact on Physiological Balance—A Holistic Approach in a Rat Model

Figures

• 

  Figure 1. Dose-dependent effects of DOX in cardiovascular and respiratory parameters: (a) systolic, (b) diastolic, and (c) mean blood pressure. (d) Heart rate values were obtained from the electrocardiogram and (e) respiratory rate was calculated from tracheal pressure. Measurements were taken in all experimental groups: CTL, DOX8, DOX16, and DOX20. Values are mean ± SEM. * p < 0.05, ** p < 0.01, *** p < 0.001 for comparison to CTL group, one-way ANOVA, Dunnett’s multiple comparisons tests. # p < 0.05, ## p < 0.01 for comparison intergroup, unpaired Student t-test.

• 

  Figure 2. The histograms show the effect of different DOX dosages on baroreflex gain and chemoreflex variation. (a) BRG was calculated from the heart rate and blood pressure variation after phenylephrine stimulation. (b) Chemoreceptor reflex sensitivity is calculated from the variation in respiratory rate upon lobeline stimulation. Values are mean ± SEM. * p < 0.05 for comparison to CTL group, one-way ANOVA, Dunnett’s multiple comparisons tests. ## p < 0.01 and ### p < 0.001 for comparison intergroup, unpaired Student t-test.

• 

  Figure 3. Dose-dependent DOX effect on sympathetic and parasympathetic tone. The sympathetic output was assessed by (a) LF, the parasympathetic output by (b) HF, and the balance between sympathetic and parasympathetic tone by (c) LF/HF ratio in all experimental groups: CTL, DOX8, DOX16, and DOX20. Values are mean ± SEM. * p < 0.05 and ** p < 0.01 for comparison to CTL group one-way ANOVA, Dunnett´s multiple comparisons tests.

• 

  Figure 4. Dose-dependent effects of DOX on urinary adrenaline, noradrenaline, and dopamine. (a) The urinary concentration of adrenaline, (b) noradrenaline, and (c) dopamine were assessed in all experimental groups: CTL, DOX8, DOX16, and DOX20. Values are mean ± SEM. No statistical differences were observed.

• 

  Figure 5. Representative images of collagen deposits in heart tissue in (a) CTL, (b) DOX8, (c) DOX16, and (d) DOX20 groups stained with picrosirius red. Arrows indicate the collagen fibers in the tissue. The scale bar provided in the image indicates that each mark corresponds to a length of 1 mm. The histograms (e) show the effect of different DOX dosages on the heart fibrotic area. The heart fibrotic area percentage was accessed by dividing the fibrotic area by the total area from all experimental groups: CTL, DOX8, DOX16, and DOX20. Values are mean ± SEM. * p < 0.05 for comparison to CTL group, one-way ANOVA, Dunnett´s multiple comparisons tests. #### p < 0.0001 for comparison intergroup, unpaired student t-test.