Linnik O O, Drevytska T I, Gonchar O O, Chornyy S A, Kovalyov O M, Mankovska I M
Fiziol Zh (1994). 2015;61(5):90-8. doi: 10.15407/fz61.05.090.
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%).
研究了阿霉素对新生心肌细胞HIF系统和抗氧化前平衡的影响，以及使用姜黄素纠正氧化应激的可能性。结果显示，使用0.5μM剂量的阿霉素时，mRNA HIF-1α的表达量为2.9±0.8 cu，与对照组（3.6±0.7 cu）相比降低了20%（P<0.05）。HIF靶基因PDK-1的表达水平也显著降低（降低了4倍）。与阿霉素孵育期间，活细胞数量相对于对照组减少了50.4%。阿霉素和姜黄素联合使用后，与仅使用阿霉素相比，死细胞百分比降低了7.7%。阿霉素中毒导致心肌细胞中脂质过氧化的次级产物（TBARS）显著增加3.6倍，过氧化氢增加64%。与对照组相比，长时间与阿霉素孵育使Mn-SOD的酶活性降低了32%，而过氧化氢酶活性增加了72%。向心肌细胞培养物中添加姜黄素使Mn-SOD活性增加了14%，过氧化氢酶活性增加了23%。与对照组相比，TBARS水平增加了1.4倍，H2O2水平增加了20%。与单独使用阿霉素的效果不同，阿霉素和姜黄素联合使用导致自由基氧化显著减少。具体而言，TBARS和H2O2减少（分别减少56.7%和18.4%），而过氧化氢酶过度激活减少（19%），Mn-SOD活性增加（35%）。
