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In vivo Liver Endocytosis Followed by Purification of Liver Cells by Liver Perfusion
Published on: November 10, 2011
Nitric oxide mediates hepatocyte injury
J H Wang1, H P Redmond, Q D Wu
1The Royal College of Surgeons in Ireland, Department of Surgery, Beaumont Hospital, Dublin 9, Ireland.
The American Journal of Physiology
|November 14, 1998
Summary
Nitric oxide (NO) induces hepatocyte (HC) apoptosis, contributing to liver injury after trauma and sepsis. This study clarifies the distinct roles of NO and reactive oxygen intermediates (ROI) in HC cell death.
Area of Science:
- Hepatology
- Cell Biology
- Immunology
Background:
- Acute hepatic failure is linked to hepatocyte (HC) damage and death via necrosis or apoptosis.
- Tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS) induce HC necrosis, not apoptosis.
- Reactive oxygen intermediates (ROI) and nitric oxide (NO) are implicated in apoptosis, but their role in HC cell death is unclear.
Purpose of the Study:
- To investigate the distinct roles of NO and ROI in hepatocyte (HC) cell death.
- To test the hypothesis that NO and ROI exert different effects on HC cell death.
Main Methods:
- Hepatocytes (HC) were treated with TNF-alpha and LPS, alone or with antioxidants.
- The effects of NO donors and nitric oxide synthase inhibitors (L-NMMA) on HC apoptosis were assessed.
- ROI generation, peroxynitrite formation, and hepatocellular enzyme release were measured.
Main Results:
- TNF-alpha and LPS with antioxidants induced HC apoptosis and DNA fragmentation, correlated with increased NO production.
- The NO donor sodium nitroprusside caused HC apoptosis and cell damage.
- Antioxidants inhibited TNF-alpha- and LPS-mediated ROI and peroxynitrite formation.
- NO synthase inhibition (L-NMMA) attenuated TNF-alpha- and LPS-induced HC apoptosis.
Conclusions:
- Nitric oxide (NO) plays a significant role in hepatocyte (HC) injury, primarily by inducing apoptosis.
- Distinct mechanisms govern HC necrosis and apoptosis in response to inflammatory stimuli.
- Targeting NO pathways may offer therapeutic strategies for liver injury in sepsis and trauma.
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