2017
DOI: 10.3389/fphar.2017.00753
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Impairment of Mitochondrial Biogenesis and Dynamics Involved in Isoniazid-Induced Apoptosis of HepG2 Cells Was Alleviated by p38 MAPK Pathway

Abstract: Isoniazid (INH), a widely used first-line antitubercular drug, has been noted to be associated with hepatotoxicity. In spite of extensive researches over many decades, the mechanism of INH-induced hepatotoxicity still remains poorly understood. Recently, mitochondrial toxicity has been emerging as a new paradigm for INH-induced hepatotoxicity. In this study, we showed that INH impaired mitochondrial biogenesis and dynamics in human hepatocarcinoma HepG2 cells. INH reduced mitochondrial membrane potential (MMP)… Show more

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Cited by 39 publications
(31 citation statements)
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References 59 publications
(83 reference statements)
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“…The INH reactive metabolite, hydrazine, was shown to directly inhibit the activity of solubilized complex II in mouse hepatocytes while causing mitochondrial oxidant stress [135]. This INH induced mitochondrial oxidative stress affects mitochondrial dynamics in various ways [136]: INH induced mitochondrial ROS and reduced the membrane potential in rat liver mitochondria [115]. This was similarly demonstrated in HepG2 cells in which INH not only reduced the membrane potential but also induced mitochondrial swelling [136] and led to changes in mitochondrial structure and its perinuclear localization [136, 137].…”
Section: Rifampin and Isoniazid Hepatotoxicitymentioning
confidence: 99%
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“…The INH reactive metabolite, hydrazine, was shown to directly inhibit the activity of solubilized complex II in mouse hepatocytes while causing mitochondrial oxidant stress [135]. This INH induced mitochondrial oxidative stress affects mitochondrial dynamics in various ways [136]: INH induced mitochondrial ROS and reduced the membrane potential in rat liver mitochondria [115]. This was similarly demonstrated in HepG2 cells in which INH not only reduced the membrane potential but also induced mitochondrial swelling [136] and led to changes in mitochondrial structure and its perinuclear localization [136, 137].…”
Section: Rifampin and Isoniazid Hepatotoxicitymentioning
confidence: 99%
“…This INH induced mitochondrial oxidative stress affects mitochondrial dynamics in various ways [136]: INH induced mitochondrial ROS and reduced the membrane potential in rat liver mitochondria [115]. This was similarly demonstrated in HepG2 cells in which INH not only reduced the membrane potential but also induced mitochondrial swelling [136] and led to changes in mitochondrial structure and its perinuclear localization [136, 137]. In INH treated lymphoma cells, the fluorescent probe JC-1 revealed a breakdown of the mitochondrial membrane potential [138].…”
Section: Rifampin and Isoniazid Hepatotoxicitymentioning
confidence: 99%
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