Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-γ in Mice

Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-γ in Mice
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胡椒碱通过激活 PPAR-γ 减轻小鼠阿霉素引起的心脏毒性

DOI:
10.1155/2019/2601408
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发表时间:
2019-12-17
期刊:
影响因子:
2.9
通讯作者:
Tang, Qi-Zhu
Tang, Qi-Zhu
中科院分区:
医学3区
文献类型:
--
作者:
Yan, Jie;Xu, Si-Chi;Tang, Qi-Zhu

文献摘要

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背景。氧化应激、炎症和心脏凋亡与阿霉素(DOX)诱导的心脏损伤密切相关。据报道,胡椒碱可抑制巨噬细胞的炎症反应和细胞焦亡。然而,胡椒碱是否可以保护小鼠免受阿霉素相关的心脏损伤仍不清楚。本研究旨在探讨胡椒碱是否能抑制 DOX 相关的小鼠心脏损伤。方法。为了诱导 DOX 相关的急性心脏损伤,DOX 组小鼠腹腔注射单剂量 DOX(15 mg/kg)。为了研究胡椒碱的保护作用,在注射 DOX 前两周开始,对小鼠口服胡椒碱(50 mg/kg,每天 18:00)3 周。结果。胡椒碱治疗显着减轻了 DOX 引起的心脏损伤,并改善了心脏功能。胡椒碱还可以减少注射 DOX 的小鼠的心肌氧化应激、炎症和细胞凋亡。胡椒碱还可以提高细胞活力,减少心肌细胞的氧化损伤和炎症因子。我们还发现胡椒碱可激活过氧化物酶体增殖物激活受体-γ (PPAR-γ),并且在体内和体外用 PPAR-γ 拮抗剂治疗可消除胡椒碱的保护作用。结论。胡椒碱可以通过激活小鼠体内的 PPAR-γ 来抑制 DOX 相关的心脏损伤。
Background. Oxidative stress, inflammation and cardiac apoptosis were closely involved in doxorubicin (DOX)-induced cardiac injury. Piperine has been reported to suppress inflammatory response and pyroptosis in macrophages. However, whether piperine could protect the mice against DOX-related cardiac injury remain unclear. This study aimed to investigate whether piperine inhibited DOX-related cardiac injury in mice. Methods. To induce DOX-related acute cardiac injury, mice in DOX group were intraperitoneally injected with a single dose of DOX (15 mg/kg). To investigate the protective effects of piperine, mice were orally treated for 3 weeks with piperine (50 mg/kg, 18:00 every day) beginning two weeks before DOX injection. Results. Piperine treatment significantly alleviated DOX-induced cardiac injury, and improved cardiac function. Piperine also reduced myocardial oxidative stress, inflammation and apoptosis in mice with DOX injection. Piperine also improved cell viability, and reduced oxidative damage and inflammatory factors in cardiomyocytes. We also found that piperine activated peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and the protective effects of piperine were abolished by the treatment of the PPAR-gamma antagonist in vivo and in vitro. Conclusions. Piperine could suppress DOX-related cardiac injury via activation of PPAR-gamma in mice.