Laboratório de Toxicologia Veterinária, Departamento de Medicina Veterinária, Escola de Veterinária e Zootecnia, Universidade Federal de Goiás, Goiânia, Brazil.
Laboratório de Toxicologia Veterinária, Departamento de Clínica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Cardiovasc Toxicol. 2020 Jun;20(3):222-234. doi: 10.1007/s12012-019-09547-4.
In the present study, we investigated the cardioprotective effects of coenzyme Q10 (Q10) against doxorubicin (DOXO) induced cardiomyopathy. Twenty adult rats were distributed in four experimental groups: group 1 received NaCl 0.9% at 1 ml/day for 14 days; group 2 received Q10 at 1 mg/kg/day for 14 days; group 3 received initial 7 days of treatment with NaCl 0.9% followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of NaCl; and group 4 received initial 7 days of Q10 1 mg/kg/day, followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of Q10. At the end of 14 days, systolic, diastolic and mean blood pressure, electrocardiogram (ECG), complete blood count, and serum biochemical profile were evaluated. We also analyzed heart histological and ultrastructure analysis, and estimated heart's oxidative stress and lipid peroxidation. DOXO administration altered ECG, with increase heart rate, P-wave duration, PR interval duration, and T-wave amplitude. All the parameters were significantly reduced following Q10 treatment. DOXO also caused increase in CK, CK-MB, LDH, and urea levels, which were not mitigated by Q10 treatment. However, Q10 reduced oxidative stress by interfering with superoxide dismutase, significantly decreasing lipid peroxidation in heart tissue. DOXO administration also leads to several histological and ultrastructure alterations including cardiomyocyte degeneration and intense intracelullar autophagosomes, all minimized by Q10 treatment. Q10 treatment prevented the ECG changes, minimized oxidative stress, lipid peroxidation, and DOXO-induced heart tissue alterations. Our findings suggest that pre- and post-treatment with Q10 exerts potential cardioprotective effect against the DOX-induced cardiotoxicity.
在本研究中，我们研究了辅酶 Q10（Q10）对阿霉素（DOXO）诱导的心肌病的心脏保护作用。将 20 只成年大鼠分为四组：第 1 组每天给予 0.9%NaCl 1ml，共 14 天；第 2 组每天给予 Q10 1mg/kg，共 14 天；第 3 组先给予 0.9%NaCl 7 天，然后给予单次阿霉素（12.5mg/kg 腹腔注射），再给予 7 天 0.9%NaCl；第 4 组先给予 Q10 1mg/kg 7 天，然后给予单次阿霉素（12.5mg/kg 腹腔注射），再给予 7 天 Q10。14 天后，评估收缩压、舒张压和平均血压、心电图（ECG）、全血细胞计数和血清生化谱，还分析了心脏组织学和超微结构，估计心脏的氧化应激和脂质过氧化。DOXO 给药改变了 ECG，导致心率、P 波持续时间、PR 间期持续时间和 T 波幅度增加。Q10 治疗后，所有参数均显著降低。DOXO 还导致 CK、CK-MB、LDH 和尿素水平升高，Q10 治疗并未减轻这些升高。然而，Q10 通过干扰超氧化物歧化酶降低了氧化应激，显著减少了心脏组织中的脂质过氧化。DOXO 给药还导致包括心肌细胞变性和细胞内自噬体增多在内的多种组织学和超微结构改变，Q10 治疗可减轻这些改变。Q10 治疗可预防 ECG 改变，减轻氧化应激、脂质过氧化和 DOXO 诱导的心脏组织改变。我们的研究结果表明，Q10 的预先和后处理对 DOXO 诱导的心脏毒性具有潜在的心脏保护作用。
