Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan.
Toxicol Appl Pharmacol. 2011 Dec 15;257(3):437-48. doi: 10.1016/j.taap.2011.10.001. Epub 2011 Oct 8.
Propofol is an anesthetic with pluripotent cytoprotective properties against various extrinsic insults. This study was designed to examine whether this agent could also ameliorate the infamous toxicity of doxorubicin, a widely-used chemotherapeutic agent against a variety of cancer diseases, on myocardial cells.
Cultured neonatal rat cardiomyocytes were administrated with vehicle, doxorubicin (1μM), propofol (1μM), or propofol plus doxorubicin (given 1h post propofol). After 24h, cells were harvested and specific analyses regarding oxidative/nitrative stress and cellular apoptosis were conducted.
Trypan blue exclusion and MTT assays disclosed that viability of cardiomyocytes was significantly reduced by doxorubicin. Contents of reactive oxygen and nitrogen species were increased and antioxidant enzymes SOD1, SOD2, and GPx were decreased in these doxorubicin-treated cells. Mitochondrial dehydrogenase activity and membrane potential were also depressed, along with activation of key effectors downstream of mitochondrion-dependent apoptotic signaling. Besides, abundance of p53 was elevated and cleavage of PKC-δ was induced in these myocardial cells. In contrast, all of the above oxidative, nitrative and pro-apoptotic events could be suppressed by propofol pretreatment.
Propofol could extensively counteract oxidative/nitrative and multiple apoptotic effects of doxorubicin in the heart; hence, this anesthetic may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application.
丙泊酚是一种具有多种细胞保护特性的麻醉剂，可抵抗各种外在刺激。本研究旨在研究该药物是否还可以减轻多柔比星（一种广泛用于治疗多种癌症的化学治疗药物）对心肌细胞的恶名昭著的毒性。
将培养的新生大鼠心肌细胞用载体、多柔比星（1μM）、丙泊酚（1μM）或丙泊酚加多柔比星（在给予丙泊酚后 1 小时给予）处理。24 小时后，收获细胞并进行有关氧化/硝化应激和细胞凋亡的特定分析。
台盼蓝排除和 MTT 测定表明，多柔比星可显著降低心肌细胞的活力。这些多柔比星处理的细胞中活性氧和氮物种的含量增加，抗氧化酶 SOD1、SOD2 和 GPx 的含量减少。线粒体脱氢酶活性和膜电位也降低，同时激活了线粒体依赖性凋亡信号下游的关键效应子。此外，这些心肌细胞中的 p53 含量增加，PKC-δ 的裂解被诱导。相比之下，丙泊酚预处理可以抑制所有上述氧化、硝化和促凋亡事件。
丙泊酚可广泛拮抗多柔比星在心脏中的氧化/硝化和多种凋亡作用；因此，这种麻醉剂可用作佐剂，以减轻多柔比星在临床应用中的不良心脏作用。
