Polynitroxyl albumin plus tempol attenuates liver injury and inflammation after hepatic ischemia and reperfusion.

Abstract

PNA+Tempol, albumin containing conjugated (polynitroxyl albumin; PNA) and free (4-hydroxyl-2,2,6,6-tetramethyl-piperidinyl-1-oxyl; Tempol) nitroxide may protect against injury caused by reactive oxygen species. Therefore, the actions of PNA+Tempol on liver injury and inflammation induced by hepatic ischemia and reperfusion (I/R) were examined. Rats were subjected to 1 h ischemia followed by 24 h reperfusion in the absence (I/R) or presence of PNA+Tempol (25%; 15 mL/kg, i.v.) (I/R+PNA+Tempol) or human serum albumin (23%; 13.5 mL/kg, i.v.) (I/R+HSA). Test solutions were administered prior to and for 2 h during reperfusion. Sham-operated rats underwent surgery with neither ischemia nor infusion. I/R+PNA+Tempol rats had significantly less liver injury and inflammation than I/R rats. I/R+PNA+Tempol livers exhibited focal lesions whereas I/R livers exhibited global necrosis. Likewise, plasma ALT activity was significantly lower in I/R+PNA+Tempol rats. PNA+Tempol reduced I/R-induced neutrophil accumulation and intercellular adhesion molecule-1 (ICAM-1) expression. HSA did not alter I/R-induced liver injury or inflammation. Sham-operated rats exhibited normal liver morphology and no inflammation. Attenuation of I/R liver injury by PNA+Tempol may be mediated by its effect on inflammation, the major contributor to I/R injury. Reduction of inflammation by PNA+Tempol is most likely due to the antioxidative nature of the nitroxides.

• Authors: J M Blonder, T A McCalden, C J Hsia, R E Billings
• Journal: Life sciences (Life Sci) Vol. 67 Issue 26 Pg. 3231-9 (Nov 17 2000) ISSN: 0024-3205 [Print] Netherlands
• PMID: 11191630 (Publication Type: Journal Article)

Chemical References

• Albumins
• Cyclic N-Oxides
• Nitrogen Oxides
• Protective Agents
• Reactive Oxygen Species
• Spin Labels
• polynitroxyl-albumin
• Intercellular Adhesion Molecule-1
• tempol

Topics

• Albumins (pharmacology)
• Animals
• Cyclic N-Oxides (pharmacology)
• Hepatitis (metabolism, pathology, prevention & control)
• Intercellular Adhesion Molecule-1 (metabolism)
• Ischemia
• Liver (blood supply, drug effects, pathology)
• Male
• Necrosis
• Neutrophils (metabolism)
• Nitrogen Oxides (pharmacology)
• Protective Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (prevention & control)
• Spin Labels