Key result
Co-administration of curcumin and doxorubicin improved mitochondrial respiration, increasing the active breathing index (V3) by 25% compared to doxorubicin alone in rat cardiomyocytes.
Why the study?
Does curcumin improve mitochondrial function and cardiomyocyte viability in doxorubicin-induced oxidative stress in rats and neonatal cardiomyocytes?
Does curcumin improve mitochondrial function and cardiomyocyte viability in doxorubicin-induced oxidative stress in rats and neonatal cardiomyocytes?
Effect estimate: 25% increase
Absolute Event Rate: 44.7% vs 35.8%
p-value: p=<0.05
Curcumin mitigates doxorubicin-induced oxidative stress and improves mitochondrial function and viability in cardiomyocytes, suggesting a potential cardioprotective role against anthracycline toxicity.
Hypothesis-generating for curcumin in anthracycline models; leaves open translation to clinical cardioprotection.
We studied the effect of curcumin on the cardiomyocytes viability, processes of oxidative phosphorylation in the mitochondria of cardiomyocytes, their pro- and antioxidant balance in doxorubicin-induced oxidative stress. It has been revealed that administration of doxorubicin to rats led to a significant increase in the secondary products of lipid peroxidation (TBARS) in mitochondria by 21 and H(2)0(2) by 76%, reduction of the enzymatic activity of mitochondrial Mn-SOD by 14% and intensified catalase activity by 80% compared with the control. After combined use of doxorubicin and curcumin the content of TBARS and H(2)0(2) increased by 14 and 26%, respectively, the enzymatic activity of catalase decreased by 28%, and mitochondrial Mn-SOD activity intensified by 9%. During the incubation with doxorubicin, the number of live cells decreased by 30.4% and the number of necrotic cells increased by 30.4% relative to control. Coadministration of doxorubicin and curcumin led to augmented cell viability by 8%, while the number of necrotic cells reduced by 8% compared with the use of doxorubicin only. In assessing the parameters of mitochondrial respiration in rats that received injections of doxorubicin active breathing index (V(3)) fell by 43.8%, the oxidation rate of the contingency of phosphorylation (V(3)/V(4)(ATp)) decreased by 47% and phosphorylation efficiency index (ADP/O) also declined by 31.7% respectively compared with the control. The combined use of doxorubicin and curcumin improved the indicators of mitochondrial respiration compared to using only doxorubicin: V(3) raised by 25%, V(3)/V(4)(ATP)by 18% and ADP/O by 12% respectively.
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Linnik et al. (2017) studied Doxorubicin-induced oxidative stress (n=17). Curcumin vs. Doxorubicin alone was evaluated on Active breathing index (V3) of myocardial mitochondria (nmol·min⁻¹·mg⁻¹ protein) (25% increase, p=<0.05). Co-administration of curcumin and doxorubicin improved mitochondrial respiration, increasing the active breathing index (V3) by 25% compared to doxorubicin alone in rat cardiomyocytes.
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