Pharm Sci. 2017;23(2):95-102.
doi: 10.15171/PS.2017.15

Scopus id: 85023168305
  Abstract View: 705
  PDF Download: 720

Research Article

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

Akram Jamshidzadeh 1,2, Hossein Niknahad 1,2, Reza Heidari 1 * , Maryam Azadbakht 2, Forouzan Khodaei 2, Mohammad Reza Arabnezhad 2, Omid Farshad 2,3

1 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
2 Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
3 Students Research Committee, School of Pharmacy, International Branch, Shiraz University of Medical Sciences, Shiraz, Iran.

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.

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Submitted: 26 Jan 2017
Accepted: 05 May 2017
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