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Autophagy-based intervention strategy in the management of hepatotoxicity.

SIGNIFICANCE
Ample evidence has demonstrated an important role for autophagy as either a protective mechanism or a cause for hepatotoxicity, denoting the likely potentials for targeting autophagy in the prevention or treatment of hepatotoxicity.


RECENT ADVANCES
The functional role of autophagy is in the pathogenesis of hepatotoxicity has been gradually recognized. Mechanistically, autophagy-mediated either protective or promoting effect on hepatotoxicity is attributed to its functions to regulate oxidative stress, endoplasmic reticulum (ER) stress, lipid metabolisms, iron homeostasis, inflammatory response and programmed cell death. Targeting autophagy as a novel strategy for fighting against hepatotoxicity has demonstrated encouraging efficacy in a number of models.


CRITICAL ISSUES
Clarifying the precise functional role of autophagy in different types of hepatotoxicity is essential for developing the type-specific autophagy-based intervention. Unraveling the molecular targets and identifying novel agents for effectively and accurately manipulating autophagy are needed for a better utilization of autophagy-based approach to exert beneficial effect on hepatotoxicity.


FUTURE DIRECTIONS
Well-designed clinical trials are needed to validate the efficacy of autophagy-targeting strategy for hepatotoxicity intervention. Further studies should be also focused on developing novel autophagy-targeting agents that can accurately regulate autophagy based on the characteristics of each type of hepatotoxicity.