Characterizing the mechanism of thiazolidinedione-induced hepatotoxicity: An in vitro model in mitochondria

Toxicology and Applied Pharmacology
Dan HuRi-gao Ding

Abstract

To characterize the mechanism of action of thiazolidinedione (TZD)-induced liver mitochondrial toxicity caused by troglitazone, rosiglitazone, and pioglitazone in HepaRG cells. Human hepatoma cells (HepaRG) were treated with troglitazone, rosiglitazone, or pioglitazone (12.5, 25, and 50μM) for 48h. The Seahorse Biosciences XF24 Flux Analyzer was used to measure mitochondrial oxygen consumption. The effect of TZDs on reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry. The mitochondrial ultrastructure of HepaRG cells was observed under a transmission electrical microscope (TEM). mtDNA content was evaluated by real-time PCR, and ATP content and mitochondrial respiratory chain (MRC) complex I, II, III, IV activity were measured via chemiluminescence. Results were considered statistically significant at p<0.05. Among the three drugs, troglitazone exhibited the highest potency, followed by rosiglitazone, and then pioglitazone. The TZDs caused varying degrees of mitochondrial respiratory function disorders including decreases in oxygen consumption, MRC activity, and ATP level, and an elevation in ROS level. TZD treatment resulted in mtDNA content decline, reduction in MMP, and alte...Continue Reading

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Citations

Nov 28, 2015·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Muzeeb SyedSteen Honoré Hansen
Oct 25, 2016·Mitochondrion·Madhusudanarao Vuda, Ashwin Kamath
Nov 13, 2018·Journal of Cellular Physiology·Habib YaribeygiAmirhossein Sahebkar
Feb 8, 2020·Journal of Inherited Metabolic Disease·Maaike C De VriesMichelangelo Mancuso
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Jan 11, 2017·Journal of Biomedical Science·Ting-Wei LeeYi-Jen Chen
May 13, 2017·The Journal of Toxicological Sciences·Yosuke SanukiKazuyuki Tsurui
May 7, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sarah HatherellAlistair M Middleton
Sep 29, 2018·Science Advances·Alexander MedvedevSergei S Makarov
Nov 2, 2019·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Bernard Fromenty

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