Qin Yeyu, Xie Jing, Zheng Ruihe, Li Yuhang, Wang Haixia
Department of Pharmacy, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.
Medical College, Xiamen University, Xiamen, China.
Front Pharmacol. 2022 Apr 20;13:863322. doi: 10.3389/fphar.2022.863322. eCollection 2022.
Doxorubicin (DOX) is one of the most common chemotherapeutic anti-cancer drugs. However, its clinical use is restricted by serious cardiotoxicity. Oleoylethanolamide (OEA), a structural congener of endocannabinoid anandamide, is the endogenous agonist of peroxisome proliferator activated-receptor α (PPARα) and transient receptor potential cation channel vanilloid-1 (TRPV1), and involved in many physiological processes. The present study aimed to determine whether OEA treatment protects against DOX-induced cytotoxicity (DIC) and gain insights into the underlying mechanism that mediate these effects. Our data revealed that Oleoylethanolamide treatment improved the myocardial structure in DOX-challenged mice by attenuating cardiac oxidative stress and cell apoptosis. OEA also alleviated DOX-induced oxidative stress and apoptosis dysregulation in HL-1 cardiomyocyte. These effects were mediated by activation of TRPV1 and upregulation of PI3K/ Akt signaling pathway. Inhibition of TRPV1 and PI3K reversed the protective effects of OEA. Taken together, our data suggested that OEA protects against DIC through a TRPV1- mediated PI3K/ Akt pathway.
阿霉素（DOX）是最常用的化疗抗癌药物之一。然而，其临床应用受到严重心脏毒性的限制。油酰乙醇胺（OEA）是内源性大麻素花生四烯乙醇胺的结构类似物，是过氧化物酶体增殖物激活受体α（PPARα）和瞬时受体电位阳离子通道香草酸受体1（TRPV1）的内源性激动剂，并参与许多生理过程。本研究旨在确定OEA治疗是否能预防阿霉素诱导的细胞毒性（DIC），并深入了解介导这些作用的潜在机制。我们的数据显示，油酰乙醇胺治疗通过减轻心脏氧化应激和细胞凋亡，改善了阿霉素攻击小鼠的心肌结构。OEA还减轻了阿霉素诱导的HL-1心肌细胞氧化应激和凋亡失调。这些作用是由TRPV1的激活和PI3K/Akt信号通路的上调介导的。抑制TRPV1和PI3K可逆转OEA的保护作用。综上所述，我们的数据表明，OEA通过TRPV1介导的PI3K/Akt途径预防DIC。
