DOXORUBICIN-INDUCED ALTERATIONS IN PRO–AND ANTIOXIDANT BALANCE AND THEIR CORRECTION BY CURCUMIN IN THE NEONATAL RAT CARDIOMYOCYTES CULTURE
O. Linnik, T. Drevytska, O. Gonchar, S. Chornyy, O. Kovalyov, I. Mankovska
O.O. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv
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 (Р<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 Н2О2 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 Н2О2 (at 56.7 and 18.4% respectively), while
decreasing of the catalase hyperactivation (19%) and rising
of the Mn-SOD activity (35%).
oxidative stress, cardiomyocytes, HIF-1α, doxorubicin, curcumin.
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