Retnosari Rini, Abdul Ghani Muhamad Adib, Majed Alkharji Munirah, Wan Nawi Wan Nur Izzah Shazana, Ahmad Rushdan Ahmad Syafi, Mahadi Mohd Kaisan, Ugusman Azizah, Oka Natsuhisa, Zainalabidin Satirah, Latip Jalifah
Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, UKM, 43600, Bangi, Selangor, Malaysia.
International Joint Department of Materials Science and Engineering Between National University of Malaysia and Gifu University, Graduate School of Engineering, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.
Cardiovasc Toxicol. 2025 Feb;25(2):167-181. doi: 10.1007/s12012-024-09940-8. Epub 2024 Nov 26.
Doxorubicin (DOX) is a remarkable chemotherapeutic agent, however, its adverse effect on DOX-induced cardiotoxicity (DIC) is a rising concern. Recent research has identified carvacrol (CAR), an antioxidant and anti-inflammatory agent, as a promising natural compound for protecting against DIC. This study aims to investigate the potential cardioprotective effects properties of CAR in vitro and in vivo. The cardioprotective effect of CAR was assessed by pretreating H9c2 cells with non-toxic CAR for 24 h, followed by co-treatment with DOX (10 μM) for an additional 24 h. The cell viability was determined using an MTT assay. For the in vivo study, male Sprague-Dawley rats (200-250 g) were randomly divided into three groups: control, cardiotoxicity (DOX), and treatment (CAR + DOX) groups. CAR (50 mg/kg, BW) was administered orally to the CAR + DOX groups for 14 days. Then, a single dose of DOX (15 mg/kg/i.p, BW) was administered on day 15 for DOX and CAR + DOX groups. The rats were allowed to recover for 3 days before being sacrificed. Our results demonstrated that DOX (10 µM) significantly reduced H9c2 cell viability by 50% (p < 0.0001), and CAR (0.067 µM) protected H9c2 cells from DIC (p = 0.0045). In the rat model, CAR pretreatment effectively mitigated DOX-induced reductions in systolic pressure (p = 0.0007), pulse pressure (p = 0.0213), hypertrophy (p = 0.0049), and cardiac fibrosis (p = 0.0006). However, the pretreatment did not alter the heart function, oxidative stress, and antioxidant enzymes. In conclusion, our results indicate that CAR could potentially serve as an adjuvant to reduce cardiotoxicity by ameliorating myocardial fibrosis and hypertrophy.
阿霉素（DOX）是一种显著的化疗药物，然而，其对阿霉素诱导的心脏毒性（DIC）的不良影响日益受到关注。最近的研究已确定香芹酚（CAR），一种抗氧化和抗炎剂，是一种有望预防DIC的天然化合物。本研究旨在调查CAR在体外和体内的潜在心脏保护作用特性。通过用无毒的CAR预处理H9c2细胞24小时，然后与DOX（10μM）共同处理24小时来评估CAR的心脏保护作用。使用MTT法测定细胞活力。对于体内研究，将雄性Sprague-Dawley大鼠（200-250g）随机分为三组：对照组、心脏毒性（DOX）组和治疗（CAR+DOX）组。向CAR+DOX组口服给予CAR（50mg/kg，体重），持续14天。然后，在第15天对DOX组和CAR+DOX组给予单剂量的DOX（15mg/kg/腹腔注射，体重）。让大鼠恢复3天，然后处死。我们的结果表明，DOX（10μM）使H9c2细胞活力显著降低50%（p<0.0001），而CAR（0.067μM）保护H9c2细胞免受DIC（p=0.0045）。在大鼠模型中，CAR预处理有效减轻了DOX诱导的收缩压降低（p=0.0007）、脉压降低（p=0.0213）、肥大（p=0.0049）和心脏纤维化（p=0.0006）。然而，预处理并未改变心脏功能、氧化应激和抗氧化酶。总之，我们的结果表明，CAR可能通过改善心肌纤维化和肥大而潜在地作为一种辅助药物来降低心脏毒性。
