Decreased hepatic ischemia-reperfusion injury by manganese-porphyrin complexes.
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 mouse 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.
Wu
Tzong-Jin
TJ
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Khoo
Nicholas H
NH
Zhou
Fen
F
Day
Brian J
BJ
Parks
Dale A
DA
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D007511:Ischemia / Q000188:drug therapy*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000098:blood supply / Q000187:drug effects*; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D015538:Nitrosation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D000975:Antioxidants; D008665:Metalloporphyrins; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C520506:manganese tetrakis-(N-ethyl-2 pyridyl) porphyrin; C520507:manganese tetrakis-(N-methyl-2 pyridyl) porphyrin; C520505:manganese tetrakis-(ethoxycarbonyl) porphyrin; C002744:3-nitrotyrosine; D014443:Tyrosine; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase