Arecoline induces cardiotoxicity by upregulating and activating cardiac hypertrophy-related pathways in Sprague-Dawley rats

被引：20

作者：

Ho, Tsung-Jung ^{[1
,2
,3
]}

Tsai, Bruce Chi-Kang ^{[4
]}

Kuo, Chia-Hua ^{[5
,6
]}

Luk, Hsiang-Ning ^{[7
]}

Day, Cecilia Hsuan ^{[8
]}

Hsieh, Dennis Jine-Yuan ^{[9
]}

Chen, Ray-Jade ^{[10
]}

Kuo, Wei-Wen ^{[16
,17
]}

Kumar, V. Bharath ^{[15
]}

Yao, Chun-Hsu ^{[11
,12
,13
,14
]}

Huang, Chih-Yang ^{[4
,15
,18
,19
,20
]}

机构：

[1] HualienTzu Chi Hosp, Integrat Ctr Tradit Chinese & Modern Med, Hualien, Taiwan

[2] Hualien Tzu Chi Hosp, Dept Chinese Med, Hualien, Taiwan

[3] Tzu Chi Univ, Coll Med, Sch Postbaccalaure Ate Chinese Med, Hualien, Taiwan

[4] Buddhist Tzu Chi Med Fdn, Hualien Tzu Chi Hosp, Cardiovasc & Mitochondrial Related Dis Res Ctr, Hualien, Taiwan

[5] Univ Taipei, Lab Exercise Biochem, Taipei, Taiwan

[6] Coll William & Mary, Dept Kinesiol & Hlth Sci, Williamsburg, VA USA

[7] Buddhist Tzu Chi Med Fdn, Hualien Tzu Chi Hosp, Dept Anesthesia, Hualien, Taiwan

[8] MeiHo Univ, Dept Nursing, Pingtung, Taiwan

[9] Chung Shan Med Univ, Dept Med Lab & Biotechnol, Taichung, Taiwan

[10] Taipei Med Univ, Coll Med, Sch Med, Dept Surg, Taipei, Taiwan

[11] China Med Univ, Dept Biomed Imaging & Radiol Sci, Taichung, Taiwan

[12] China Med Univ, Sch Chinese Med, Taichung, Taiwan

[13] China Med Univ Hosp, Biomat Translat Res Ctr, Taichung, Taiwan

[14] Asia Univ, Dept Bioinformat & Med Engn, Taichung, Taiwan

[15] Asia Univ, Dept Med Lab Sci & Biotechnol, Taichung, Taiwan

[16] China Med Univ, Coll Life Sci, Dept Biol Sci & Technol, Taichung, Taiwan

[17] China Med Univ, PhD Program Biotechnol Ind, Taichung, Taiwan

[18] Tzu Chi Univ Sci & Technol, Buddhist Tzu Chi Med Fdn, Ctr Gen Educ, Hualien, Taiwan

[19] China Med Univ, Grad Inst Biomed Sci, Taichung, Taiwan

[20] China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung, Taiwan

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 2022年 / 354卷

关键词：

Areca nut; Arecoline; Cardiac toxicity; IL-6; MAPK; Calcineurin; TRANSCRIPTION FACTORS; ARECA NUT; BETEL; ROLES; HEART; STAT;

D O I：

10.1016/j.cbi.2022.109810

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Habitual chewing of the areca nut increases the risk of mortality owing to cardiovascular disease, but few reports have revealed the cardiotoxicity mechanism of the areca nut. Arecoline has been reported to be the primary toxic constituent in the areca nut. In order to study the acute cardiotoxicity of the areca nut in the development of pathologic heart hypertrophy, we induced heart injury in rats using arecoline. Arecoline at a low dosage (5 mg/kg/day) or a high dosage (50 mg/kg/day) was intraperitoneally injected to Sprague-Dawley rats for 21 days. The change of heart function and biochemical pathways were investigated with echocardiography and Western blot. The results were presented that heart functions were weakened by arecoline stimulation, and western blotting analysis revealed an elevation in BNP levels in the heart after arecoline exposure. Arecoline induced IL-6-mediated activation of the MEK5/ERK5 and JAK2/STAT3 pathways, as well as mitogen-activated protein kinase signaling cascades. Further, arecoline increased the calcineurin and NFATc3 levels in the heart. In summary, our results suggest that arecoline causes significantly cardiotoxicity and heart damage by inducing several hypertrophy-related signaling pathways, including IL-6-induced MEK5/ERK5, JAK2/STAT3, mitogen-activated protein kinases, and calcineurin signaling pathways. The study elucidated, for the first time, the possible cardiac hypertrophy mechanisms underlying the cardiotoxicity of the areca nut.

引用

页数：9

共 48 条

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