Decreased hepatic ischemia-reperfusion injury by manganese-porphyrin complexes

• Published in: Free radical research 2007, Vol.41 (2), p.127-134
• Main Authors: Wu, Tzong-Jin, Khoo, Nicholas H., Zhou, Fen, Day, Brian J., Parks, Dale A.
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - secretion; Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; Aspartate Aminotransferases - secretion; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; free radical; Ischemia; Ischemia - drug therapy; L-Lactate Dehydrogenase - secretion; Lipid Peroxidation - drug effects; liver; Liver - blood supply; Liver - drug effects; Liver Diseases - prevention & control; Male; metallophoryrin; Metalloporphyrins - pharmacology; Metalloporphyrins - therapeutic use; Mice; Mice, Inbred C57BL; nitric oxide; Nitrosation - drug effects; Reactive Oxygen Species - metabolism; Reperfusion Injury - prevention & control; Thiobarbituric Acid Reactive Substances - analysis; Tyrosine - analogs & derivatives; Tyrosine - analysis
• ISSN: 1071-5762; 1029-2470
• DOI: 10.1080/10715760600801298

Reactive oxygen and nitrogen species have been implicated in ischemia-reperfusion (I/R) injury. Metalloporphyrins (MP) are stable catalytic antioxidants that can scavenge superoxide, hydrogen peroxide, peroxynitrite and lipid peroxyl radicals. Studies were conducted with three manganese-porphyrin (MnP) complexes with varying superoxide dimutase (SOD) and catalase catalytic activity to determine if the MnP attenuates I/R injury in isolated perfused rat livers. The release of the hepatocellular enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) was maximal at 1 min reperfusion, decreased rapidly and increased gradually by 90 min. Manganese tetrakis-(N-ethyl-2 pyridyl) porphyrin (MnTE-2-PyP) decreased ALT, AST, LDH at 1-90 min reperfusion, while manganese tetrakis-(N-methyl-2 pyridyl) porphyrin (MnTM-2-PyP) and manganese tetrakis-(ethoxycarbonyl) porphyrin (MnTECP) decreased ALT and LDH from 5 to 90 min reperfusion. The release of thiobarbituric acid-reacting substances (TBARS) was diminished by MnTE-2-PyP and MnTM-2-PyP at 90 min. The extent of protein nitration (nitrotyrosine, NT) was decreased in all three MnPs treated livers. These results demonstrate that MnP complexes can attenuate hepatic I/R injury and may have therapeutic implications in disease states involving oxidants.