The effects of N -acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by a choline-methionine-deficient diet

Abstract

tory injury is involved in hypothermic I/R injury, that oxidaAbundant fat in the liver has been implicated in poor outtive stress produced by PMNLs is involved in normothermic come after liver transplantation or liver surgery, but the rea-I/R injury, and that NAC and anti-rat ICAM-1 monoclonal sons for this association are still unclear. The aim of the antibody restore liver integrity in I/R injury. (HEPATOLOGY present study was to examine mechanisms that may be in-1997;26:670-678.) volved in hepatic dysfunction after ischemia-reperfusion (I/R) of the steatotic rat liver. Steatosis was produced by a cholinemethionine-deficient (CMDD) diet. In the first experiment,In clinical liver transplantation, donor livers may be subisolated perfused rat livers, subjected to 24-hour cold storage jected to various types of stress, such as ischemia caused by followed by 120-minute reperfusion, were used to investigate hypotension or drug-induced liver dysfunction. Steatotic hypothermic I/R injury of the steatotic rat liver. In the second liver grafts have recently been directly implicated in primary experiment, livers were subjected to 60-minute partial left graft nonfunction or dysfunction after orthotopic liver translobar vascular clamping to allow study of normothermic I/R plantation in humans. [1][2][3] The poor outcome of transplantainjury. In the first experiment, compared with normal non-tion of steatotic liver grafts has also been confirmed in animal steatotic liver, steatotic livers showed significantly greater in-models. [4][5][6] Furthermore, emergency liver transplantation is jury, as assessed by amounts of hepatic enzymes released into often required because liver failure may develop postoperathe perfusate, bile production, the concentrations of reduced tively when a steatotic liver has been partially resected and glutathione (GSH) in the perfusate, as well as in the livers Pringle's maneuver has been performed for 60 minutes or themselves, and electron microscopic findings of sinusoidal more. 7 The vulnerability of steatotic liver to normothermic microcirculatory injury. The addition of N-acetylcysteine ischemia-reperfusion (I/R) has also been shown experimen-(NAC), a precursor of glutathione, to the liver before cold tally. 8 However, mechanisms of I/R injury in the steatotic storage significantly improved these parameters in steatotic liver have not been fully clarified. Elucidation of these mechlivers. The second experiment showed that, compared with anisms and development of appropriate treatments are more nonsteatotic livers, steatotic livers had lower concentrations important than ever because of the severe shortage of donor of GSH and impaired rates of bile production. There was also organs. evidence of increased oxidative stress in polymorphonuclear N-Acetylcysteine (NAC) is a precursor of glutathione, leukocytes (PMNLs) in liver or peripheral blood of rats with which has been shown to be effective for the treatment of fatty livers. An anti-rat intercellular adhesion molecule-1 fulminant liver failure aft...

Bucillamine, a thiol antioxidant, prevents transplantation-associated reperfusion injury

“…A previous study similarly observed a significant reduction in the level of GSH in steatotic livers induced by a choline-methionine-deficient diet compared with that in normal livers (28). Low GSH levels may underlie the greater susceptibility of steatotic livers to reperfusion injury.…”

“…The antioxidant enzyme superoxide dismutase had variable effectiveness in previous studies and has been most impressive when administered by gene therapy with viral vectors, an as-yet-unproven technology (12). N-acetylcysteine, especially at high doses, has been successful in preserving microcirculatory function in some studies but has been ineffective in others (28,(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). In a pilot clinical study, it also seemed to improve outcomes in patients (46).…”

N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation

“…In rat liver transplantation, NAC treatment reduced early phase reperfusion injury [5] and decreased leucocyte adherence to sinusoidal endothelium [23]. In a model of hypothermic I/R injury of the steatotic rat liver, NAC given before cold storage for 24 h diminished sinusoidal microcirculatory injury and lowered enzyme release after reperfusion [24]. In an endotoxin sepsis model of the rat, NAC treatment given before as well as after induction of sepsis decreased leucocyte adherence in mesentery vessels and improved haemodynamics [25,26].…”

Effect of Hepatic Steatosis on Bioenergetic Function During Hepatic Ischemia-reperfusion: A Systematic Review

“…1). One study by Nakano et al examined the effect of hepatic steatosis on bioenergetics in both warm and cold IRI [17].…”

“…QUORUM Diagram. [18]; b, [19]; c, [20]; d, [21]; e, [22]; f, [23], g, [24]; h, [25]; i, [26]; j, [27]; k, [28]; l, [29]; m, [30]; n, [17]; o, [31]; p, [32]; q, [33]; r, [34]; s, [35]; t, [36]; u, [37] [38]; b, [39]; c, [40]; d, [41]; e, [42]; f, [43]; g, [44]; h, [45]; i, [46]; j, [47]; k, [48]; l, [49]; m, [50]; n, [51]; o, [52] [62]; c, [63]; d, [64]; e, [65]; f, [66]; g, [67]; h, [68]; i, [69]; j, [70]; k, [71]; l, [17]; m, [60]; n, [72]; o, [73]<...>…”