Key result
Co-administration of doxorubicin and curcumin in neonatal rat cardiomyocytes reduced TBARS and H2O2 levels by 56.7% and 18.4%, respectively, and increased Mn-SOD activity by 35% compared to doxorubicin alone.
Why the study?
Does curcumin reduce doxorubicin-induced oxidative stress and cell death in neonatal rat cardiomyocytes?
Does curcumin reduce doxorubicin-induced oxidative stress and cell death in neonatal rat cardiomyocytes?
p-value: p=<0.05
Curcumin partially protects neonatal rat cardiomyocytes from doxorubicin-induced oxidative stress and cytotoxicity by modulating antioxidant enzyme activity.
Supports preclinical exploration of curcumin with doxorubicin; leaves open clinical translation and safety.
It was studied the effect of doxorubicin on the HIF system and the pro-antioxidant balance of neonatal cardiomyocytes as well as the possibility of the oxidative stress correcting using curcumin. It has been revealed that the expression of mRNA HIF-1α using doxorubicin at a dose of 0.5 μM was 2.9 ± 0.8 cu, so it decreased by 20% compared to control--3.6 ± 0.7 cu (P < 0.05). The level of expression of the HIF target gene PDK-1 also significantly decreased (4 times). During the incubation with doxorubicin, the number of live cells decreased by 50.4% relative to control. And after using doxorubicin and curcumin together, the percentage of dead cells decreased by 7,7 compared to doxorubicin only. Doxorubicin intoxication led to a significant increase in the secondary products of lipid peroxidation (TBARS) in cardiomyocytes by 3.6 times and hydrogen peroxide by 64%. Prolonged incubation with doxorubicin reduced the enzymatic activity of Mn-SOD by 32%, while catalase activity increased by 72% compared to control. Adding of curcumin to the cardiomyocyte cell culture contributed to increasing of the Mn-SOD activity by 14%, catalase--by 23%. The level of TBARS increased by 1,4 times compared with the control, and the level of H2O2 increased by 20%. The joint use of doxorubicin and curcumin resulted in a significant reduction of free radical oxidation unlike effect of doxorubicin per se. Specifically, there was lessening of TBARS and H2O2 (at 56.7 and 18.4% respectively), while decreasing of the catalase hyperactivation (19%) and rising of the Mn-SOD activity (35%).
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Linnik et al. (2015) studied Doxorubicin-induced oxidative stress. Curcumin vs. Doxorubicin alone (0.5 µmol/ml) was evaluated on Oxidative stress markers (TBARS and H2O2 levels) (p=<0.05). Co-administration of doxorubicin and curcumin in neonatal rat cardiomyocytes reduced TBARS and H2O2 levels by 56.7% and 18.4%, respectively, and increased Mn-SOD activity by 35% compared to doxorubicin alone.
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