The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats
The areca nut is one of the most commonly consumed psychoactive substances worldwide, with an estimated consumption by approximately 10% of the world’s population, especially in some regions of South Asia, East Africa, and the tropical Pacific. Arecoline, the major areca nut alkaloid, has been class...
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De Gruyter
2021
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oai:doaj.org-article:d6546e3a9d3943768d9d3689cac3eeed2021-12-05T14:10:42ZThe molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats2391-541210.1515/biol-2021-0116https://doaj.org/article/d6546e3a9d3943768d9d3689cac3eeed2021-11-01T00:00:00Zhttps://doi.org/10.1515/biol-2021-0116https://doaj.org/toc/2391-5412The areca nut is one of the most commonly consumed psychoactive substances worldwide, with an estimated consumption by approximately 10% of the world’s population, especially in some regions of South Asia, East Africa, and the tropical Pacific. Arecoline, the major areca nut alkaloid, has been classified as carcinogenic to humans as it adversely affects various organs, including the brain, heart, lungs, gastrointestinal tract, and reproductive organs. Earlier studies have established a link between areca nut chewing and cardiac arrhythmias, and yet research pertaining to the mechanisms underlying cardiotoxicity caused by arecoline is still preliminary. The main purpose of this study is to test the hypothesis that arecoline causes cardiac fibrosis through transforming growth factor-β (TGF-β)/Smad-mediated signaling pathways. Male Wistar rats were injected intraperitoneally with low (5 mg/kg/day) or high (50 mg/kg/day) doses of arecoline for 3 weeks. Results from Masson’s trichrome staining indicated that arecoline could induce cardiac fibrosis through collagen accumulation. Western blot analysis showed that TGF-β and p-Smad2/3 protein expression levels were markedly higher in the arecoline-injected rat hearts than in those of the control rats. Moreover, arecoline upregulated other fibrotic-related proteins, including SP1-mediated connective tissue growth factor expression. Tissue-type plasminogen activator and its inhibitor, plasminogen activator inhibitor, and matrix metalloproteinase (MMP) 9 were upregulated, and the inhibitor of MMP9 was downregulated. This study provides novel insight into the molecular mechanisms underlying arecoline-induced cardiac fibrosis. Taken together, the areca nut is a harmful substance, and the detrimental effects of arecoline on the heart are similar to that caused by oral submucous fibrosis.Ku Chang-WenDay Cecilia HsuanOu Hsiu-ChungHo Tsung-JungChen Ray-JadeKumar Velmurugan BharathLin Wen-YuanHuang Chih-YangDe Gruyterarticlearecolinecardiac fibrosistgf-βmmp9smadBiology (General)QH301-705.5ENOpen Life Sciences, Vol 16, Iss 1, Pp 1182-1192 (2021) |
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arecoline cardiac fibrosis tgf-β mmp9 smad Biology (General) QH301-705.5 |
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arecoline cardiac fibrosis tgf-β mmp9 smad Biology (General) QH301-705.5 Ku Chang-Wen Day Cecilia Hsuan Ou Hsiu-Chung Ho Tsung-Jung Chen Ray-Jade Kumar Velmurugan Bharath Lin Wen-Yuan Huang Chih-Yang The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats |
| description |
The areca nut is one of the most commonly consumed psychoactive substances worldwide, with an estimated consumption by approximately 10% of the world’s population, especially in some regions of South Asia, East Africa, and the tropical Pacific. Arecoline, the major areca nut alkaloid, has been classified as carcinogenic to humans as it adversely affects various organs, including the brain, heart, lungs, gastrointestinal tract, and reproductive organs. Earlier studies have established a link between areca nut chewing and cardiac arrhythmias, and yet research pertaining to the mechanisms underlying cardiotoxicity caused by arecoline is still preliminary. The main purpose of this study is to test the hypothesis that arecoline causes cardiac fibrosis through transforming growth factor-β (TGF-β)/Smad-mediated signaling pathways. Male Wistar rats were injected intraperitoneally with low (5 mg/kg/day) or high (50 mg/kg/day) doses of arecoline for 3 weeks. Results from Masson’s trichrome staining indicated that arecoline could induce cardiac fibrosis through collagen accumulation. Western blot analysis showed that TGF-β and p-Smad2/3 protein expression levels were markedly higher in the arecoline-injected rat hearts than in those of the control rats. Moreover, arecoline upregulated other fibrotic-related proteins, including SP1-mediated connective tissue growth factor expression. Tissue-type plasminogen activator and its inhibitor, plasminogen activator inhibitor, and matrix metalloproteinase (MMP) 9 were upregulated, and the inhibitor of MMP9 was downregulated. This study provides novel insight into the molecular mechanisms underlying arecoline-induced cardiac fibrosis. Taken together, the areca nut is a harmful substance, and the detrimental effects of arecoline on the heart are similar to that caused by oral submucous fibrosis. |
| format |
article |
| author |
Ku Chang-Wen Day Cecilia Hsuan Ou Hsiu-Chung Ho Tsung-Jung Chen Ray-Jade Kumar Velmurugan Bharath Lin Wen-Yuan Huang Chih-Yang |
| author_facet |
Ku Chang-Wen Day Cecilia Hsuan Ou Hsiu-Chung Ho Tsung-Jung Chen Ray-Jade Kumar Velmurugan Bharath Lin Wen-Yuan Huang Chih-Yang |
| author_sort |
Ku Chang-Wen |
| title |
The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats |
| title_short |
The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats |
| title_full |
The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats |
| title_fullStr |
The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats |
| title_full_unstemmed |
The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats |
| title_sort |
molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats |
| publisher |
De Gruyter |
| publishDate |
2021 |
| url |
https://doaj.org/article/d6546e3a9d3943768d9d3689cac3eeed |
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