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

作者: Akram Jamshidzadeh , Hossein Niknahad , Reza Heidari , Maryam Azadbakht , Forouzan Khodaei

DOI: 10.15171/PS.2017.15

关键词:

摘要: Background: Propylthiouracil (PTU) administration is associated with several cases of hepatotoxicity, especially in children. The mechanism(s) PTU-induced hepatotoxicity obscure. In the current study, we aimed to assess effect PTU on hepatocytes mitochondria different experimental models. Methods: Mice were treated (10, 20, 40, 80, and 100 mg/kg, i.p) then, liver mitochondria were isolated evaluated. Moreover, liver were isolated from normal mice incubated increasing concentrations PTU (10 µM-1 mM). Mitochondrial dehydrogenases activity, mitochondrial membrane potential, swelling, adenosine triphosphate (ATP) content monitored. Results: PTU hepatotoxicity was biochemically evident by increased serum biomarkers of injury. also caused a decrease in swelling, depleted ATP, caused mitochondrial depolarization both vitro vivo. Conclusion: Our data suggest dysfunction as mechanism for PTU-induced hepatotoxicity.

参考文章(52)
Jun Yang, Lin-fa Li, Qin Xu, Jun Zhang, Wan-wen Weng, Yang-jun Zhu, Meng-jie Dong, Analysis of 90 cases of antithyroid drug-induced severe hepatotoxicity over 13 years in China. Thyroid. ,vol. 25, pp. 278- 283 ,(2015) , 10.1089/THY.2014.0350
Meng-Ting Wang, Wan-Ju Lee, Tien-Yu Huang, Che-Li Chu, Chang-Hsun Hsieh, Antithyroid drug-related hepatotoxicity in hyperthyroidism patients: a population-based cohort study. British Journal of Clinical Pharmacology. ,vol. 78, pp. 619- 629 ,(2014) , 10.1111/BCP.12336
Katie Chan, Don Truong, Nandita Shangari, Peter J O’Brien, Drug-induced mitochondrial toxicity. Expert Opinion on Drug Metabolism & Toxicology. ,vol. 1, pp. 655- 669 ,(2005) , 10.1517/17425255.1.4.655
Rob C.A. Onderwater, Jan N.M. Commandeur, Nico P.E. Vermeulen, Comparative cytotoxicity of N-substituted N′-(4-imidazole-ethyl)thiourea in precision-cut rat liver slices Toxicology. ,vol. 197, pp. 81- 91 ,(2004) , 10.1016/J.TOX.2003.11.014
Ping Zhao, Thomas F. Kalhorn, John T. Slattery, Selective mitochondrial glutathione depletion by ethanol enhances acetaminophen toxicity in rat liver Hepatology. ,vol. 36, pp. 326- 335 ,(2002) , 10.1053/JHEP.2002.34943
Dennis R. Lock, Zev M. Sthoeger, Severe hepatotoxicity on beginning propylthiouracil therapy. Journal of Clinical Gastroenterology. ,vol. 24, pp. 267- 269 ,(1997) , 10.1097/00004836-199706000-00020
Reza Heidari, Hossein Niknahad, Akram Jamshidzadeh, Narges Abdoli, Factors affecting drug-induced liver injury: antithyroid drugs as instances Clinical and molecular hepatology. ,vol. 20, pp. 237- 248 ,(2014) , 10.3350/CMH.2014.20.3.237
Rob C.A Onderwater, Jan N.M Commandeur, Ed J Groot, Astrid Sitters, Wiro M.P.B Menge, Nico P.E Vermeulen, Cytotoxicity of a series of mono- and di-substituted thiourea in freshly isolated rat hepatocytes: a preliminary structure-toxicity relationship study Toxicology. ,vol. 125, pp. 117- 129 ,(1998) , 10.1016/S0300-483X(97)00169-8