Paradoxical effect of methimazole on liver mitochondria: In vitro and in vivo. (30th September 2016)

• Record Type: Journal Article
• Authors: Niknahad, Hossein; Jamshidzadeh, Akram; Heidari, Reza; Hosseini, Zeynab; Mobini, Keivan; Khodaei, Forouzan; Ommati, Mohammad Mehdi; Abdoli, Narges; Keshavarz, Nahid; Bazyari, Mandana; Najibi, Asma
• Is Part Of: Toxicology letters. Volume 259(2016)
• Page Start: 108
• Page End: 115
• Publication Date: 2016-09-30
• Subjects: Antithyroids hepatotoxicity -- Methimazole -- Liver injury -- Mitochondria -- Glyoxal; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2016.08.003
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: Methimazole caused mitochondrial injury when it was administered to mice ( in vivo ). Paradoxically methimazole not only caused no injury toward isolated mitochondria ( in vitro ), but also protected this organelle against stress. Methimazole seems to be a novel mitochondrial protecting agent in vitro . Abstract: Methimazole is the most frequently prescribed antithyroid agent. On the other hand, several cases of liver injury are attributed to this drug. The mechanism of methimazole-induced liver injury is obscure. Hepatocytes mitochondria seem to be a target for methimazole cytotoxicity. Current investigation aimed to evaluate the effects of methimazole on the hepatocytes mitochondria in different experimental models. In the in vivo model, methimazole (100, 200 and 400 mg/kg, i.p) was administered to mice and liver mitochondria were isolated and assessed. In the in vitro experiments, intact isolated liver mitochondria were incubated with increasing methimazole concentrations (10 μM–100 mM). It was found that methimazole decreased liver mitochondrial ATP and glutathione, increased mitochondrial swelling, lipid peroxidation and reactive oxygen species (ROS), and collapsed mitochondrial membrane potential when administered to mice. Paradoxically, methimazole not only caused no significant injury toward isolated liver mitochondria in vitro but improved mitochondrial function and protected this organelle. The differences between two investigated models in the current study might be associated with drug bioactivation and reactive metabolites formation. These findings suggest mitochondrial dysfunction as a mechanism for methimazole-induced liver injury. Moreover, methimazole seems to be a novel mitochondrial protecting agent in vitro .