The Postulated Hepatotoxic Metabolite of Methimazole Causes Mitochondrial Dysfunction and Energy Metabolism Disturbances in Liver

Niknahad, Hossein and Jamshidzadeh, Akram and Heidari, Reza and Abdoli, Narges and Ommati, Mohammad Mehdi and Jafari, Faezeh and Zarei, Mahdi and Asadi, Behnam (2016) The Postulated Hepatotoxic Metabolite of Methimazole Causes Mitochondrial Dysfunction and Energy Metabolism Disturbances in Liver. Pharmaceutical Sciences, 22 (4). pp. 217-226. ISSN 1735-403X

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Abstract

Background: Although several cases of methimazole-induced liver injury are reported, but there is no clear idea on the mechanism of methimazole hepatotoxicity. N-methyl thiourea (NMT) is a postulated hepatotoxic metabolite for methimazole. The current investigation was designed to evaluate the effect of NMT on hepatocyte mitochondria as a target of xenobiotics-induced cellular injury. Methods: Isolated liver mitochondria from healthy mice were incubated with NMT (10 µM-160 mM) (in vitro). Furthermore, mice received NMT (10, 20, 40 and 80 mg/kg, i.p) then, their liver mitochondria were isolated and assessed (in vivo). Several mitochondrial indices including mitochondrial succinate dehydrogenase activity, mitochondrial membrane potential, mitochondrial swelling, reactive oxygen species, lipid peroxidation, and mitochondrial glutathione and ATP content were assessed. Results: NMT caused a decrease in succinate dehydrogenase activity, an increase in mitochondrial ROS formation, lipid peroxidation, and swelling along with the collapse of mitochondrial membrane potential in both in vitro and in vivo experiments. Moreover, the level of glutathione and ATP was lower in NMT-exposed mitochondria. Conclusion: Our data indicate that mitochondrial dysfunction might play a major role in the mechanism of liver injury induced by the methimazole hepatotoxic metabolite.

Item Type: Article
Subjects: ScienceOpen Library > Medical Science
Depositing User: Managing Editor
Date Deposited: 09 May 2023 05:29
Last Modified: 02 Sep 2024 12:25
URI: http://scholar.researcherseuropeans.com/id/eprint/1198

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