Polynitroxyl albumin plus tempol attenuates liver injury and inflammation after hepatic ischemia and reperfusion.
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.
Blonder
J M
JM
RxKinetix, Inc., Louisville, CO 80027, USA. joan@rxkinetix.com
McCalden
T A
TA
Hsia
C J
CJ
Billings
R E
RE
D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D006505:Hepatitis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007511:Ischemia; D008099:Liver / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009336:Necrosis; D009504:Neutrophils / Q000378:metabolism; D009589:Nitrogen Oxides / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D013113:Spin Labels
D000418:Albumins; D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D020011:Protective Agents; D017382:Reactive Oxygen Species; D013113:Spin Labels; C117059:polynitroxyl-albumin; D018799:Intercellular Adhesion Molecule-1; C001803:tempol