Department of Cardiology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
Department of Pharmacology, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.
Mol Biol Rep. 2024 Apr 18;51(1):532. doi: 10.1007/s11033-024-09488-4.
Doxorubicin is an effective antineoplastic agent but has limited clinical application because of its cumulative toxicities, including cardiotoxicity. Cardiotoxicity causes lipid peroxidation, genetic impairment, oxidative stress, inhibition of autophagy, and disruption of calcium homeostasis. Doxorubicin-induced cardiotoxicity is frequently tried to be mitigated by phytochemicals, which are derived from plants and possess antioxidant, anti-inflammatory, and anti-apoptotic properties. Arbutin, a natural antioxidant found in the leaves of the bearberry plant, has numerous pharmacological benefits, including antioxidant, anti-bacterial, anti-hyperglycemic, anti-inflammatory, and anti-tumor activity.
The study involved male Wistar rats divided into three groups: a control group, a group treated with doxorubicin (20 mg/kg) to induce cardiac toxicity, a group treated with arbutin (100 mg/kg) daily for two weeks before doxorubicin administration. After treatment, plasma and heart tissue samples were collected for analysis. The samples were evaluated for oxidative stress parameters, including superoxide dismutase, malondialdehyde, and catalase, as well as for cardiac biomarkers, including CK, CK-MB, and LDH. The heart tissues were also analyzed using molecular (TNF-α, IL-1β and Caspase 3), histopathological and immunohistochemical methods (8-OHDG, 4 Hydroxynonenal, and dityrosine). The results showed that arbutin treatment was protective against doxorubicin-induced oxidative damage by increasing SOD and CAT activity and decreasing MDA level. Arbutin treatment was similarly able to reverse the inflammatory response caused by doxorubicin by reducing TNF-α and IL-1β levels and also reverse the apoptosis by decreasing caspase-3 levels. It was able to prevent doxorubicin-induced cardiac damage by reducing cardiac biomarkers CK, CK-MB and LDH levels. In addition to all these results, histopathological analyzes also show that arbutin may be beneficial against the damage caused by doxorubicin on heart tissue.
The study suggests that arbutin has the potential to be used to mitigate doxorubicin-induced cardiotoxicity in cancer patients.
多柔比星是一种有效的抗肿瘤药物，但由于其累积毒性，包括心脏毒性，临床应用受到限制。心脏毒性导致脂质过氧化、遗传损伤、氧化应激、自噬抑制和钙稳态破坏。多柔比星诱导的心脏毒性常试图通过植物化学物质来减轻，这些化学物质来源于植物，具有抗氧化、抗炎和抗凋亡特性。熊果苷是一种存在于熊果叶中的天然抗氧化剂，具有许多药理作用，包括抗氧化、抗菌、抗高血糖、抗炎和抗肿瘤活性。
本研究涉及雄性 Wistar 大鼠，分为三组：对照组、用多柔比星（20mg/kg）处理组以诱导心脏毒性、用熊果苷（100mg/kg）处理组，每天处理两周，然后给予多柔比星。治疗后，采集血浆和心脏组织样本进行分析。评估了氧化应激参数，包括超氧化物歧化酶、丙二醛和过氧化氢酶，以及心脏生物标志物，包括 CK、CK-MB 和 LDH。还使用分子（TNF-α、IL-1β 和 Caspase 3）、组织病理学和免疫组织化学方法（8-OHDG、4-羟壬烯醛和二酪氨酸）分析心脏组织。结果表明，熊果苷通过增加 SOD 和 CAT 活性和降低 MDA 水平，对多柔比星诱导的氧化损伤具有保护作用。熊果苷还能通过降低 TNF-α 和 IL-1β 水平来减轻多柔比星引起的炎症反应，并通过降低 caspase-3 水平来逆转细胞凋亡。它还能通过降低心脏标志物 CK、CK-MB 和 LDH 水平来防止多柔比星引起的心脏损伤。除了所有这些结果，组织病理学分析还表明，熊果苷可能对多柔比星对心脏组织造成的损伤有益。
该研究表明，熊果苷有可能用于减轻癌症患者多柔比星引起的心脏毒性。
