propylthiouraci-linduced mitochondrial dysfunction in liver and its relevance to drug-induced hepatotoxicity

Background: propylthiouracil (ptu) administration is associated with several cases of hepatotoxicity, especially in children. the mechanism(s) of ptu- induced hepatotoxicity is obscure. in the current study, we aimed to assess the effect of ptu on hepatocytes mitochondria in different experimental models. methods: mice were treated with ptu (10, 20, 40, 80, and 100 mg/kg, i.p) then, the liver mitochondria were isolated and evaluated. moreover, liver mitochondria were isolated from normal mice and incubated with increasing concentrations of ptu (10 µm-1 mm). mitochondrial dehydrogenases activity, mitochondrial membrane potential, mitochondrial swelling, and mitochondrial adenosine triphosphate (atp) content were monitored. results: ptu hepatotoxicity was biochemically evident in mice by increased serum biomarkers of liver injury. ptu also caused a decrease in mitochondrial dehydrogenases activity, increased mitochondrial swelling, depleted mitochondrial atp, and caused mitochondrial depolarization both in vitro and in vivo. conclusion: our data suggest mitochondrial dysfunction as a mechanism for ptu-induced hepatotoxicity.