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Journal : Narra J

Colchicine attenuates chemical hypoxia-induced pyroptosis through downregulation of nuclear factor kappa B and caspase-1 in cardiomyocytes Satrijo, Budi; Rohman, Mohammad S.; Aulanni'am, Aulanni'am; Sujuti, Hidayat; Lestari, Bayu
Narra J Vol. 5 No. 2 (2025): August 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i2.2245

Abstract

Myocardial infarction (MI) is the leading cause of mortality worldwide. During MI, cardiomyocyte necrosis and inflammation are crucial in the post-MI cardiac remodeling process, including pyroptosis. Although colchicine is a well-known anti-inflammatory drug that has been clinically studied in the context of MI, its role in cardiac pyroptosis remains unclear. The aim of this study was to investigate the role of colchicine in pyroptosis in vitro, using CoCl2-induced H9c2 cells. Prior to the primary experiment, the hypoxic model in H9c2 cells was optimized by evaluating hypoxia-inducible factor-1 alpha (HIF-1α) expression and viability in cells exposed to various concentrations of CoCl2 at different time intervals. Subsequently, an in vitro hypoxia model was established by treating H9c2 cells with CoCl2 (600 µM), with or without colchicine (1 µM), for 3 hours. Flow cytometry was used to measure the expression of nuclear factor-kappa beta (NF-κB), interleukin 18 (IL-18), caspase-1, and HIF-1α in pyroptotic cells. Immunofluorescence was used to assess caspase-1 localization and its colocalization with propidium iodide during late-stage pyroptosis. Our data indicated that CoCl2-induced hypoxia significantly upregulated NF-κB, caspase-1, and IL-18 expression, and increased pyroptotic cell death in H9c2 cells. Colchicine treatment attenuated these effects, leading to a marked reduction in NF-κB, caspase-1, and IL-18 expression in hypoxic cells. Colchicine treatment significantly decreased the number of late pyroptotic cells. The protective effect of colchicine was more pronounced in late hypoxia (24-hour) setting compared to early hypoxia (3-hour). These findings suggest that colchicine attenuates cardiac pyroptosis in hypoxic H9c2 cells, as evidenced by the significant downregulation of key proteins involved in this pathway, including NF-κB, caspase-1, and IL-18. This protective effect appeared to be more effective in late hypoxia.
Co-Authors A. Harijono A.A. Ketut Agung Cahyawan W Abdalrauf A Mahmud Yousif Abdalrauf A Mahmud Yousif, Abdalrauf A Mahmud Abdussalam Ashour, Abdussalam Achmad Rudijanto Adinda Chika Anindita Affandi, Haykal Agung Prasetyo Wibowo Agustiana Dwi Agustiana Dwi Indiah Ventiyaningsih Agustina Tri Endharti Ala Shukri Eshami, Ala Shukri Analis W Wardhana Anik Puryatni Anisak, Siti Ariani Ariani Ariani Ariani Arifin, Mochammad Samsul Arsinah Habibah Fitriah, Arsinah Habibah Askandar Tjokroprawiro Astika Swastirani Aulanni'am, Aulanni'am Aulia Yasmin, Aulia Bagus Hermansyah Bambang Rahardjo Bayu Kurniawan Bintang Soetjahjo Bogi Pratomo Wibowo Burhan, Niniek Chabibi, Mochamad Chabibi Chairinnisa, Elsa Safira Christina Dewi Dalhar, Mochamad Dewi, Ni Ketut Ayu Feriyanti Dian Handayani Dian Nugrahenny Diana Lyrawati Diana Lyrawati Dicky Faizal Irnandi Didi Candradikusuma Didi Candradikusuma Dwi Jayasa, Pande Made Dwi Yuni Nur Hidayati Edi Mustamsir Edi Widjajanto Edi Widjajanto Edwin Widodo Effendi, Ma'sum Eko Sulistijono Elok Zubaidah Erma Sulistyaningsih Ery Olivianto Fardizia Putri Alia Feni Istikharoh Fibrianto, Yuda Fita Shofiyah Gading, Inges Manggar Gerry Gunawan, Gerry Handono Kalim Hanif Hanif Happy Kurnia Permatasari Hara, Kenta HARI PURNOMO Hariwati Hariwati Hasfiani, Yuliatin Huda Rohmawati Husna, Ully Husnul Khotimah Ika Kustiyah Oktaviyanti Indrayanti Indrayanti Indriati Dwi Rahayu Inggita Kusumastuty Josef Sem Berth Tuda Juniartha, Putu Kalsumy, Umi Kanthi Permaningtyas Tritisari, Kanthi Permaningtyas Karyono Mintaroem Karyono Mintaroem Karyono Mintaroem Karyono mitaroem, Karyono Krisni Subandiyah Krisni Subandiyah Kusworini Handono Laily Yuliatun Lavina Sofia Ardani Lely Retno W Leny Budhi Harti Lestari, Bayu Lirawati, Diana Loeki Enggar Fitri M Rasjad Indra Machlusil Husna, Machlusil Maimun Z Arthamin, Maimun Z Masafumi Matsuo Masdar Muid Masdar Muid Masruroh Rahayu Masruroh Rahayu, Masruroh Mayangsari, Elly Mentari Sekar Arum Miftahu Soleh Moch. Aris Widodo, Moch. Aris Mochammad Dalhar Mohammad Hidayat Mohammad Hidayat Mohammad S. Rohman Muhammad Ali Faisal Muhammad Rasjad Indra Muhammad Rasjad Indra Nabila Andjani, Nabila Nabila Erina Erwan Nashi Widodo Nathania Bella Claresta Niarti Ulan Sari Siarnu Nindy Sabrina Niniek Burhan Nisrina Nur Afina, Nisrina Nur Nunuk Helilusiatiningsih Nur Kusmiyati Nur Permatasari Nura Fattah Cantika Yoga Nurshalilah Nurshalilah Pande Made Dwi Jayasa Pande Made Dwijayasa Prima Wijayanti, Prima Primawardani, Putri Puryatni, Anik - Putri, Dianita Setya Pradita Putu Juniartha Raisa, Neila Raudhatul Jannah Restuningwiyani, Sintha Retnani, Diah Prabawati Retty Ratnawati Retty Ratnawati Rizky Amalia RR. Ettie Rukmigarsari Salim, Irfan Agus Samsul Arifin Santoso, Giovani Anggasta Satrijo, Budi Selvi Marcellia Septi Nur Rachmawati Setiyaningsih, Fera Yuli Setyawati Soeharto Setyawati Soeharto, Setyawati Shintiya Dewi, Debby Shofiyah, Fita SIMON BAMBANG WIDJANARKO Sintha Restuningwiyani Siti Lintang Kawuryan Siti Narsito Wulan Soetjahjo, Bintang Sri Andarini Sutrisno Sutrisno Syahrul Chilmi, Syahrul Syarifah Rohaya Tatit Nurseta Tatit Nurseta Tatit Nurseta Tika Ardhini Wardoyo Tinny Endang Tinny Endang Hernowati Tokunaga, Chiharu Tri Dewanti Widyaningsih Triawanti Triawanti Tuda, Josef Sem Berth Umar Zein Vierlia, Wino Vrieda Widowati, Hesty Widya Rahmawati Winda Nurtika Yonezawa, Kazuyoshi Yoshino, Ken-ichi Yuda Fibrianto Yudanto, Hendy Setyo Zuly Vita Aulya, Zuly Vita