Abstract
Morphological changes of hepatocyte death have so far only been described on cells in culture or in tissue sections. Using a high-resolution and high-magnification multiphoton microscopic system, we recorded in living mice serial changes of acetaminophen (APAP)-induced hepatocyte necrosis in relevance to metabolism of a fluorogenic bile solute. Initial changes of hepatocyte injury included basal membrane disruption and loss of mitochondrial membrane potential. An overwhelming event of rupture at adjacent apical membrane resulting in flooding of bile into these hepatocytes might ensue. Belbs formed on basal membrane and then dislodged into the sinusoid circulation. Transmission electron microscopy disclosed a necrotic hepatocyte depicting well the changes after apical membrane rupture and bile flooding. Administration of the antidote N-acetylcysteine dramatically reduced the occurrence of apical membrane rupture. The present results demonstrated a hidden but critical step of apical membrane rupture leading to irreversible APAP-induced hepatocyte injury.
Highlights
Multiphoton microscopy allows high-resolution imaging of cells deep in various organs of living animals.[6]
Traced back to zero time, both types of CF-retaining cells were all pre-labeled by rhodamine B isothiocyanate (RITC)-dextran, though retention tended to be less intense in early CF-retaining (ECFR) cells
new CF-retaining (NCFR) cells were not pre-labeled by RITCdextran
Summary
Multiphoton microscopy allows high-resolution imaging of cells deep in various organs of living animals.[6]. Canalicular membrane rupture resulting in bile flooding in NCFR hepatocytes. These two cells developed abrupt swelling and bile flooding, suggesting that the canalicular membrane rupture occurred at 45 min and 27 min, respectively.
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