title: Hepatic ischemia/reperfusion injury: importance of oxidant/tumor necrosis factor interactions.
abstract: Previous studies have demonstrated a role for both tumor necrosis factor (TNF) and reactive oxygen intermediates (ROI) in hepatic ischemia/reperfusion (I/R) injury. Biologically active TNF was present in liver homogenates in ischemic and nonischemic lobes after 2 h of ischemia but without reperfusion. Using an in situ liver perfusion model, we measured ROI, TNF, and hepatic enzymes in the effluent after 2 h of ischemia. Increased reduction of ferricytochrome C was observed in the hepatic effluent, indicative of the formation of ROI. Treatment of animals with TNF neutralizing antisera significantly reduced both ROI and aspartate aminotransferase (AST). Animals treated with superoxide dismutase (SOD), or SOD + catalase (CAT) had greater TNF in the hepatic effluent compared with I/R alone; however, SOD or SOD + CAT did not cause additional release of AST.SOD + CAT plus anti-TNF serum resulted in significant protection compared with SOD + CAT plus control serum. Reperfusion of ischemic liver with 4 mM H2O2 increased both TNF and AST. Optimal protection of hepatocellular injury from reperfusion injury is achieved with a combination of antioxidants and inhibition of TNF.
authors: Department of Surgery, University of Michigan Medical School, Ann Arbor 48109.
authors: W E
authors: WE
authors: Scales
authors: D A
authors: DA
authors: Campbell
authors: M E
authors: ME
authors: Green
authors: D G
authors: DG
authors: Remick
mesh_terms: D000818:Animals; D002374:Catalase / Q000494:pharmacology; D007511:Ischemia / Q000378:metabolism*; D008099:Liver / Q000098:blood supply*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D002374:Catalase; D013482:Superoxide Dismutase