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

• Published in: Life sciences (1973) 2000-11, Vol.67 (26), p.3231-3239
• Main Authors: Blonder, Joan M., McCalden, Thomas A., Hsia, Carleton J.C., Billings, Ruth E.
• Format: Article
• Language: English
• Subjects: Albumins - pharmacology; Animals; Cyclic N-Oxides - pharmacology; Hepatitis - metabolism; Hepatitis - pathology; Hepatitis - prevention & control; Intercellular Adhesion Molecule-1 - metabolism; Ischemia; Liver; Liver - blood supply; Liver - drug effects; Liver - pathology; Male; Necrosis; Neutrophils - metabolism; Nitrogen Oxides - pharmacology; Polynitroxyl albumin; Protective Agents - pharmacology; Rat; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Reperfusion; Reperfusion Injury - prevention & control; Spin Labels
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(00)00907-3

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.