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Published on: February 25, 2016
Nitric oxide synthase and postischemic liver injury
S Kawachi1, I N Hines, F S Laroux
1Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, Louisiana, 71130, USA.
Abstract:
The objective of this study was to determine what roles the endothelial cell and inducible isoforms of nitric oxide synthase (eNOS, iNOS) play in ischemia and reperfusion (I/R)-induced liver injury in vivo in mice genetically deficient in each isoform of NOS. We found that 45 min of partial (70%) liver ischemia and 5 h of reperfusion induced substantial liver injury as assessed by the release of large and significant amounts of the liver-specific enzyme alanine aminotransferase (ALT) into the serum of wild-type (wt) mice. The enhanced ALT levels were not due to increased recruitment of potentially damaging PMNs, which could mediate hepatocyte injury, as neither histopathological inspection nor quantitative MPO determinations revealed the presence of PMNs in the liver at this time point. In addition, we observed a significant enhancement in liver injury in eNOS-deficient but not iNOS-deficient mice subjected to liver I/R compared to postischemic wt mice. Taken together, these data suggest that eNOS- but not iNOS-derived NO plays an important role in limiting or downregulating I/R-induced liver injury in vivo following 5 h of reperfusion.
Insights
Endothelial nitric oxide synthase (eNOS) protects against liver injury caused by ischemia and reperfusion (I/R). Mice lacking eNOS showed worse liver damage, while those lacking inducible nitric oxide synthase (iNOS) did not.
Area of Science:
- Physiology
- Immunology
- Hepatology
Background:
- Ischemia and reperfusion (I/R) injury is a significant clinical problem.
- Nitric oxide synthase (NOS) isoforms, endothelial (eNOS) and inducible (iNOS), are implicated in I/R injury.
- The specific roles of eNOS and iNOS in liver I/R injury remain unclear.
Purpose of the Study:
- To investigate the roles of eNOS and iNOS in I/R-induced liver injury in vivo.
- To compare liver injury severity in eNOS-deficient and iNOS-deficient mice.
Main Methods:
- Induction of partial liver ischemia (70%) for 45 minutes followed by 5 hours of reperfusion in wild-type (wt), eNOS-deficient, and iNOS-deficient mice.
- Assessment of liver injury by measuring serum alanine aminotransferase (ALT) levels.
- Histopathological examination and myeloperoxidase (MPO) determination to assess neutrophil infiltration.
Main Results:
- Significant liver injury, indicated by elevated ALT, occurred in wt mice after I/R.
- No significant neutrophil infiltration was observed in the liver at the assessed time point.
- eNOS-deficient mice exhibited significantly enhanced liver injury compared to wt mice.
- iNOS-deficient mice showed no significant difference in liver injury compared to wt mice.
Conclusions:
- Endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) plays a protective role in limiting liver I/R injury.
- Inducible nitric oxide synthase (iNOS)-derived NO does not appear to play a significant role in this model of liver I/R injury.
- Targeting eNOS may offer a therapeutic strategy for mitigating liver I/R injury.
