Abstract
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.