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褪黑素对顺铂诱导的心脏毒性的保护作用:BDNF-TNF-α信号通路的潜在作用

Protective effects of melatonin in cisplatin-induced cardiac toxicity: possible role of BDNF-TNF-α signaling pathway.

作者信息

Zhuo Xiaoqing, Jiang Honglei

机构信息

MM. Department of Cardiology - Shandong Second Provincial General Hospital (Shandong ENT Hospital) - Jinan, China.

出版信息

Acta Cir Bras. 2022 May 2;37(2):e370208. doi: 10.1590/acb370208. eCollection 2022.

DOI:10.1590/acb370208
PMID:35507972
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9064185/
Abstract

PURPOSE

The present study explored the role of melatonin in cisplatin-induced cardiac injury along with the possible role of brain-derived neurotrophic factor (BDNF) in melatonin-mediated effects.

METHODS

Wistar rats were administered cisplatin (10 mg/kg), and cardiac injury was assessed by measuring the levels of cardiac troponin (cTnT) and lactate dehydrogenase (LDH-1).The extent of apoptosis was measured by measuring caspase-3 (pro-apoptotic) and Bcl-2 (anti-apoptotic) in hearts. The levels of BDNF, tumour necrosis factor α (TNF-α) and reduced glutathione were measured in heart. Melatonin (5 and 10 mg/kg) was administered for 15 days, and the role of BDNF was identified by co-administering BDNF inhibitor, ANA-12 (0.25 and 0.5 mg/kg).

RESULTS

Melatonin attenuated cTnT and LDH-1 levels along with reduction in caspase-3 and increase in Bcl-2. It also increased cisplatin-induced decrease in BDNF, increase in TNF-α and decrease in reduced glutathione levels. Moreover, ANA-12 abolished the cardioprotective effects, anti-inflammatory and antioxidant effects of melatonin suggesting the role of BDNF in melatonin-mediated effects in cisplatin-induced cardiac injury.

CONCLUSIONS

Melatonin is useful in cisplatin-induced cardiac injury, which may be due to an increase in BDNF, decrease in inflammation and increase in antioxidant activities.

摘要

目的

本研究探讨褪黑素在顺铂诱导的心脏损伤中的作用,以及脑源性神经营养因子(BDNF)在褪黑素介导的效应中的可能作用。

方法

给Wistar大鼠注射顺铂(10mg/kg),通过测量心肌肌钙蛋白(cTnT)和乳酸脱氢酶(LDH-1)水平评估心脏损伤。通过测量心脏中半胱天冬酶-3(促凋亡)和Bcl-2(抗凋亡)来测定凋亡程度。测量心脏中BDNF、肿瘤坏死因子α(TNF-α)和还原型谷胱甘肽的水平。给予褪黑素(5和10mg/kg)15天,并通过共同给予BDNF抑制剂ANA-12(0.25和0.5mg/kg)来确定BDNF的作用。

结果

褪黑素降低了cTnT和LDH-1水平,同时降低了半胱天冬酶-3水平并增加了Bcl-2水平。它还逆转了顺铂诱导的BDNF降低、TNF-α升高和还原型谷胱甘肽水平降低。此外,ANA-12消除了褪黑素的心脏保护作用、抗炎和抗氧化作用,表明BDNF在褪黑素介导的顺铂诱导的心脏损伤效应中起作用。

结论

褪黑素对顺铂诱导的心脏损伤有效,这可能是由于BDNF增加、炎症减轻和抗氧化活性增强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/11fbd51aa649/1678-2674-acb-37-2-e370208-gf07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/e3317d58f5a2/1678-2674-acb-37-2-e370208-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/5f746ccea2ff/1678-2674-acb-37-2-e370208-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/f8a5839238f8/1678-2674-acb-37-2-e370208-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/e7ea4bbe218e/1678-2674-acb-37-2-e370208-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/1a7bc85e6ca6/1678-2674-acb-37-2-e370208-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/8eec3f34ab93/1678-2674-acb-37-2-e370208-gf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/11fbd51aa649/1678-2674-acb-37-2-e370208-gf07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/e3317d58f5a2/1678-2674-acb-37-2-e370208-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/5f746ccea2ff/1678-2674-acb-37-2-e370208-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/f8a5839238f8/1678-2674-acb-37-2-e370208-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/e7ea4bbe218e/1678-2674-acb-37-2-e370208-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/1a7bc85e6ca6/1678-2674-acb-37-2-e370208-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/8eec3f34ab93/1678-2674-acb-37-2-e370208-gf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3d0/9064185/11fbd51aa649/1678-2674-acb-37-2-e370208-gf07.jpg

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