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Journal : INDONESIAN JOURNAL OF PHARMACY

Potential Deleterious Effects of L-Citrulline Supplementation in Isoproterenol-Induced Myocardial Infarction: Focus on Nitrosative Stress Gregorius Bhaskara Wikanendra; Wawaimuli Arozal; Kusmardi Kusmardi; Vetnizah Juniantito; Andrea Laurentius
Indonesian Journal of Pharmacy Vol 30 No 4, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjpharm30iss4pp269

Abstract

L-Citrulline shows potential activity as a supplement to prevent myocardial infarction through vasodilative and possible antioxidative effects but may be deleterious by causing nitrosative stress. This study determined the potentially deleterious effects of L-citrulline supplementation in isoproterenol-induced myocardial infarction with a focus on nitrosative stress. L-Citrulline supplementation was given orally at dosages of 300 or 600mg/kg body weight daily for 6 days. Myocardial infarction was induced in Wistar rats via subcutaneous injection of isoproterenol (85 mg/kg body weight (BW)) on day 4 and 5. Blood pressure was measured at the end of the study (day 6) and rats were sacrificed to collect heart tissue samples for a histopathological evaluation. The histopathological evaluation was done using hematoxylin and eosin staining for the myocardial damage evaluation and immunohistochemical (IHC) staining of arginase-2, inducible nitric oxide synthase (iNOS), and 3-nitrotyrosine to evaluate nitrosative stress. L-Citrulline supplementation failed to show a significant protective effect on blood pressure and exacerbated the decrease of diastolic blood pressure. Both low and high dose L-citrulline supplementation had a significant protective effect on myocardial damage compared to the isoproterenol group (p<0.01). L-Citrulline also caused increased nitrosative stress as shown by increased expression of arginase-2 and 3-nitrotyrosine on IHC staining but tended to show an ameliorative effect on iNOS expression. A significant increase in arginase-2 expression was detected between the high dose group and the other groups (p<0.01 vs. normal and isoproterenol groups; p<0.05 vs. low dose group). L-Citrulline supplementation increased 3-nitrotyrosine expression in a dose-dependent manner, which was significantly different compared to the normal group (low dose: p<0.013; high dose: p<0.003). L-Citrulline increased the production of nitrosative stress but resulted in less myocardial damage through its other effects.
Co-Authors Agatha Grace Agian Jeffilano Barinda Andrea Laurentius Arleni Bustami Aryo Tedjo Barinda, Again Jeffilano Bernie Endyarni Medise Cong, Tzeto Han Deni Rahmat Dewi Sukmawati Dewi, Yulia Ratna Djumhana Atmakusuma Djumhana Atmakusuma, Djumhana Dwita, Nounik Cheri Edhiatmi, Marsetyo Erlina, Linda Erni H Purwaningsih Erni H Purwaningsih, Erni H Erni Hernawati Purwaningsih, Erni Hernawati Ernie Purwaningsih Eviarini, Prawitasari Eziefule, Oluebube Magnificient Fadhillah, Muhamad Rizqy Fadilah Fadilah Fadilah, Fadilah Fajarido, Ariski Femmi Dwinda Agustini Franciscus D. Suyatna Gregorius Bhaskara Wikanendra Gusti Khatimah, Nurul Hanifah Oswari Hedi R. Dewoto Heri Wibowo Hesty Utami Husna, Fauzul Indah D Dewijanti Indah D Dewijanti, Indah D Irawan Mangunatmadja Jusman, Sri Widia Azraki Kapuangan, Christopher Kartika, Kartika Handayani Kenichi Watanabe Khatimah, Nurul Gusti Kuncoro, Daviet Dwi Kurniasari Kurniasari Kusmardi Kusmardi Kusmardi Kusmardi Laurentius, Andrea Lee, Hee Jae Marliana Sri Rejeki Marliana Sri Rejeki Marliana Sri Rejeki Marselina Marselina Marsetyo Edhiatmi Meilei Ma Melva Louisa Muhamad Sadam Safutra Musridharta, Eka Nabillah, Deya Adiby Nafrialdi Nafrialdi Nastiti Kaswandani Ni Made Dwi Sandhiutami Novi Silvia Hardiany Nur Azizah Nurwulan Adi Ismaya Pebriani, Mala Primadhani, Suci Widya Punniyakoti T. Veeraveedu Puspita Eka Wuyung Puspita Eka Wuyung Putri, Rizky Clarinta Radiana Dhewayani Antarianto Radoti Merlin Rani Hendiyani Rani Sauriasari Rani Sauriasari, Rani Raymond R. Tjandrawinata Rejeki, Marliana Sri Ria Anggraeni Rianto Setiabudy Rianto Setiabudy Riski Amanda, Clara Roro Rukmi Windi Perdani, Roro Rukmi ROS SUMARNY Ros Sumarny Rosyidah, Citra Safutra, Muhamad Sadam Safutra, Sadam Sagala, Radoti Merlin SEPTELIA INAWATI WANANDI Sesilia Keban Sesilia Keban, Sesilia Setyo Handryastuti Shimizu, Ippei Silmi Hanifah Soni Siswanto Sumiati, Yati Supraja Dwiyono Suyatna, Franciscus D Syarifah Dewi Thandavarayan, Rajarajan Amirthalingam Tri Yuliani Tri Yuliani, Tri Triana, Novi Tzeto Han Cong Ulfa T Wahyuni Ulya, Nurul Vetnizah Juniantito Vivian Soetikno Vivian Soetikno Wahyunia Likhayati Septiana Wardani, Amanda Saphira Wikanendra, Gregorius Bhaskara Yati Sumiyati