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  • Apoptosis in HepG2 cells induced by zinc Pyrithione (cas 1121-30-8) via mitochondrial dysfunction pathway: Involvement of zinc accumulation and oxidative stress
  • Add time:10/01/2019         Source:sciencedirect.com

    Zinc Pyrithione (cas 1121-30-8) (ZPT) is widely used as a substitute booster biocide for tributyltin and is also an additive to antidandruff shampoos and medical cosmetic products. ZPT and pyrithione have been detected in different environmental matrices and biota, suggesting that it may pose health threats to aquatic organisms and even humans. The present study used HepG2 cells, a human hepatoma cell line, to study the hepatotoxicity of ZPT (0.1–5.0 μM). ZPT treatment caused marked viability reduction and induced apoptosis depending on its dose used. ZPT-induced apoptosis involved an increased Bax/Bcl-2 ratio, loss of mitochondrial membrane potential, cytochrome c release, and enhanced caspase-9/-3 activity. In addition, a significant elevation in the amount of zinc ions and oxidative stress was evident. The involvement of these in ZPT-induced apoptosis was confirmed by toxicity comparison with analogs of ZPT and the observation that pretreatment with antioxidants afforded protection. Overall, these results suggest that ZPT induces zinc accumulation, oxidative stress, and subsequent apoptosis by causing mitochondrial dysfunction. Importantly, ROS was an initial and prolonged signal in ZPT-induced apoptosis in HepG2 cells.

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