High concentration of magnolol induces hepatotoxicity under serum-reduced conditions

Ying Hsien Kao, Bruno Jawan, Cheuk Kwan Sun, Shigeru Goto, Yu Chun Lin, Chun Tzu Hung, Mei Chun Pan, Li Wen Hsu, Yu Fan Cheng, Chia Yun Lai, Chih Shien Wang, Ching Chou Tsai, Huoy Rou Chang, Chao Long Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

13 Scopus citations

Abstract

Although magnolol is cytoprotective against warm ischemia/reperfusion injury, its effect on cold preservation has not been fully investigated. This study aimed at examining whether magnolol maintains the liver graft integrity after cold preservation and elucidating the underlying mechanisms in terms of apoptotic signaling under both normothermic and hypothermic conditions. After being preserved in Ringer's lactate (RL) at 4 °C for 6 h ex vivo, the magnolol-treated grafts demonstrated significantly higher AST, ALT, and LDH levels in perfusates than those from negative controls. TUNEL staining showed no difference in the number of apoptotic nuclei in both groups, whereas a more intense apoptotic signal in magnolol-treated grafts was shown as compared with the controls. In vitro data showed no significant difference in viability of RL-preserved clone-9 hepatocytes between the magnolol-treated and control groups, while magnolol pretreatment at 30 min before cold preservation prominently induced hepatocyte cell death. RT-PCR and Western blotting analyses revealed a suppression in Bcl-2, but an up-regulation in Bax expression in clone-9 cells after magnolol treatment. Magnolol suppressed the ratios of NF-κB to I-κBα protein contents and I-κBα phosphorylation induced by TNF-α, and potentiated mitochondrial cytochrome c release and subsequent caspase-3 cleavage. Conversely, caspase-3 inhibitor attenuated magnolol-induced hepatotoxicity. We concluded that magnolol could not protect liver grafts from cold ischemia/reperfusion injury. High concentration of magnolol under serum-reduced conditions attenuates NF-κB-mediated signaling and induces intrinsic apoptotic pathway, thereby inducing in vitro hepatotoxicity.

Original languageEnglish
Pages (from-to)469-474
Number of pages6
JournalPhytomedicine
Volume17
Issue number6
DOIs
StatePublished - 05 2010
Externally publishedYes

Keywords

  • Caspase-3 inhibitor
  • Cold preservation injury
  • Cytochrome c
  • Hepatotoxicity
  • Liver graft
  • Magnolia officinalis
  • Magnolol

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