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Ultrastructural effects of acetaminophen in isolated mouse hepatocytes
Abstract:
The ultrastructure of isolated mouse hepatocytes shows good correlation with that of cells from intact liver. Incubation of isolated mouse hepatocytes with 1.0 mM acetaminophen causes a variety of cytoplasmic and cell surface lesions, as well as cell death. The changes are similar or equivalent to those caused by acetaminophen in vivo. The most prominent feature of damage in isolated hepatocytes is bleb formation, which is also seen occasionally in control incubations. The protective compound alpha-mercaptopropionylglycine and the antidote N-acetylcysteine both prevented the acetaminophen-induced changes. It is suggested that the in vivo counterpart to the blebs are endocytic vacuoles which form at cell margins due to the intravascular pressure of the sinusoids. It is suggested that the cell surface changes both in vivo and in isolated hepatocytes are caused by some dysfunction to the microfilament component of the cytoskeleton.
Insights
Acetaminophen causes liver cell damage, mimicking in vivo effects in isolated mouse hepatocytes. Protective agents like N-acetylcysteine prevented these acetaminophen-induced changes, suggesting cytoskeletal involvement.
Area of Science:
- Hepatology
- Toxicology
- Cell Biology
Background:
- Isolated mouse hepatocytes serve as a model for studying drug toxicity.
- Acetaminophen is a common drug known to cause liver injury.
Purpose of the Study:
- To investigate the effects of acetaminophen on isolated mouse hepatocytes.
- To compare in vitro acetaminophen toxicity with in vivo observations.
- To explore the protective mechanisms against acetaminophen-induced liver damage.
Main Methods:
- Isolation and incubation of mouse hepatocytes.
- Exposure of hepatocytes to acetaminophen (1.0 mM).
- Microscopic examination of cellular ultrastructure and surface changes.
- Assessment of protective effects of alpha-mercaptopropionylglycine and N-acetylcysteine.
Main Results:
- Acetaminophen induced cytoplasmic and cell surface lesions, including bleb formation, in isolated hepatocytes.
- These changes mirrored those observed in vivo.
- Bleb formation was also noted in control incubations but was prominent with acetaminophen.
- Alpha-mercaptopropionylglycine and N-acetylcysteine effectively prevented acetaminophen-induced damage.
Conclusions:
- Isolated mouse hepatocytes accurately model acetaminophen-induced liver injury.
- Acetaminophen toxicity in hepatocytes involves cytoskeletal microfilament dysfunction.
- N-acetylcysteine and alpha-mercaptopropionylglycine show potential as antidotes by mitigating these cellular changes.