Tranilast prevents doxorubicin-induced myocardial hypertrophy and angiotensin II synthesis in rats.

作者: Chengchuang Zhan , Nan Bai , Min Zheng , Yanyan Wang , Yuanqi Wang

DOI: 10.1016/J.LFS.2020.118984

关键词: Oxidative stressAngiotensin IIDoxorubicinChymaseHeart diseasePharmacologyFibrosisApoptosisChemistryTranilast

摘要: An increase in oxidative stress is an important pathological mechanism of heart injury induced by doxorubicin (DOX). Tranilast anti-allergy drug that has been shown to possess good antioxidant activity previous studies. The overexpression and secretion chymase mast cells (MCs) the angiotensin II (Ang II), which plays a crucial role myocardial hypertrophy deterioration disease. MC stabilizer tranilast (N-(3,4-dimethoxycinnamoyl) anthranilic acid; tran) prevents from degranulating, may reduce DOX-induced Ang synthesis. Therefore, present study, we hypothesized will protect rats damage via its activity, thereby inhibiting expression. Thirty male Wistar were divided into three groups (n = 10 each group) received DOX, combination DOX or saline (the control test this hypothesis. suppressed expression, reduced levels prevented function DOX. Based on findings suppression chymase-dependent Ang-II production direct effect inhibition apoptosis fibrosis because capacity contribute protective against hypertrophy.

参考文章(51)
Rania R. Abdelaziz, Wagdi F. Elkashef, Eman Said, Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy. Environmental Toxicology and Pharmacology. ,vol. 40, pp. 259- 267 ,(2015) , 10.1016/J.ETAP.2015.06.019
Pawan K. Singal, Natasha Iliskovic, Timao Li, Dinender Kumar, Adriamycin cardiomyopathy: pathophysiology and prevention. The FASEB Journal. ,vol. 11, pp. 931- 936 ,(1997) , 10.1096/FASEBJ.11.12.9337145
Raymond B. Weiss, The anthracyclines: will we ever find a better doxorubicin? Seminars in Oncology. ,vol. 19, pp. 670- 686 ,(1992) , 10.5555/URI:PII:009377549290036Z
K K Griendling, B Lassègue, T J Murphy, M Clark, R W Alexander, G Nickenig, Angiotensin II down-regulates the vascular smooth muscle AT1 receptor by transcriptional and post-transcriptional mechanisms: evidence for homologous and heterologous regulation. Molecular Pharmacology. ,vol. 48, pp. 601- 609 ,(1995)
Oktay Tacar, Crispin R. Dass, Doxorubicin-induced death in tumour cells and cardiomyocytes: is autophagy the key to improving future clinical outcomes? Journal of Pharmacy and Pharmacology. ,vol. 65, pp. 1577- 1589 ,(2013) , 10.1111/JPHP.12144
Naotaka Shiota, Hideki Okunishi, Shinji Takai, Imao Mikoshiba, Hiroshi Sakonjo, Nobuo Shibata, Mizuo Miyazaki, Tranilast Suppresses Vascular Chymase Expression and Neointima Formation in Balloon-Injured Dog Carotid Artery Circulation. ,vol. 99, pp. 1084- 1090 ,(1999) , 10.1161/01.CIR.99.8.1084
Taben M Hale, Susan J Robertson, Kevin D Burns, Denis deBlois, Short-term ACE inhibition confers long-term protection against target organ damage. Hypertension Research. ,vol. 35, pp. 604- 610 ,(2012) , 10.1038/HR.2012.2
Tien Van Phan, Ke Ke, Ok-Joo Sul, Yun-Kyung Park, Kack-Kyun Kim, Yeon-Soo Cho, Hun-Taeg Chung, Hye-Seon Choi, Protection against Ovariectomy-Induced Bone Loss by Tranilast PLoS ONE. ,vol. 9, pp. e95585- ,(2014) , 10.1371/JOURNAL.PONE.0095585