Related Experiment Video
Updated: Aug 24, 2026
Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration
Published on: May 31, 2018
Simultaneous abrogation of NOS-2 and COX-2 activities is lethal in partially hepatectomised mice
Miriam Zeini1, Sonsoles Hortelano, Paqui G Través
1Instituto de Bioquímica (Centro Mixto CSIC-UCM), Facultad de Farmacia, Universidad Complutense, 28040, Madrid, Spain.
Background/Aims:
We have investigated the role of the nitric oxide (NO) and prostaglandins (PGs), respectively, synthesized by nitric oxide synthase 2 (NOS-2) and cyclooxygenase-2 (COX-2), in the outcome of liver regeneration after partial hepatectomy (PH).
Methods:
Liver mass recovery and molecular parameters related to cell proliferation and apoptotic death have been determined.
Results:
NOS-2 and COX-2 are normally both expressed in the remnant liver after PH, and inhibition of either one delays regeneration. We found, however, that simultaneous suppression of the activities of NOS-2 (by gene knockout) and COX-2 (by pharmacological inhibition) resulted in animal death between 24 and 72 h after PH. Analysis of liver mass recovery and molecular parameters related to cell proliferation and apoptotic death revealed increased liver-cell apoptosis and an insufficient proliferative response. Broad-specificity caspase inhibitors, such as z-Val-Ala-Asp.fmk (z-VAD), or administration of NO-donors, rescued animals from death, revealing a critical apoptotic bias at this stage of proliferation.
Conclusions:
These findings demonstrate that simultaneous signaling by NO and prostaglandins plays an important role in the mechanism of liver regeneration after PH by protecting the remnant tissue from apoptotic death.
Insights
Nitric oxide (NO) and prostaglandins (PGs) are crucial for liver regeneration after partial hepatectomy (PH). Simultaneous blocking of NOS-2 and COX-2 leads to death, highlighting their protective role against apoptosis.
Area of Science:
- Hepatology
- Molecular Biology
- Regenerative Medicine
Background:
- Investigating the roles of nitric oxide (NO) and prostaglandins (PGs) in liver regeneration post-partial hepatectomy (PH).
- Examining the involvement of nitric oxide synthase 2 (NOS-2) and cyclooxygenase-2 (COX-2) in liver regeneration outcomes.
Purpose of the Study:
- To elucidate the combined function of NO and PGs in liver regeneration after PH.
- To determine the impact of inhibiting NOS-2 and COX-2 on liver regeneration and survival.
Main Methods:
- Assessing liver mass recovery and molecular markers of cell proliferation and apoptosis.
- Utilizing gene knockout for NOS-2 and pharmacological inhibition for COX-2 in a PH model.
- Employing caspase inhibitors and NO-donors to evaluate rescue effects.
Main Results:
- Both NOS-2 and COX-2 are expressed in remnant liver post-PH, and inhibiting either delays regeneration.
- Simultaneous inhibition of NOS-2 and COX-2 leads to mortality within 72 hours post-PH.
- This inhibition causes increased hepatocyte apoptosis and inadequate proliferation, which can be rescued by caspase inhibitors or NO-donors.
Conclusions:
- Coordinated signaling of NO and PGs is vital for liver regeneration after PH.
- These signaling pathways protect remnant liver tissue from excessive apoptotic cell death during regeneration.
