Augmentation of Mitochondrial Reduced Glutathione by S-Adenosyl-L-Methionine Administration in Ischemia-Reperfusion Injury of the Rat Steatotic Liver Induced by Choline-Methionine-Deficient Diet

Abstract

We examined whether warm ischemia-reperfusion (I/R) damage of the rat steatotic liver can be reduced by administration of S-adenosyl-L-methionine (SAMe). We examined the effect of SAMe on the mitochondrial reduced-glutathione (GSH) pool. Sixty minutes of partial left lobar vascular clamping followed by 2 h of reperfusion were employed for a model of hepatic warm ischemia. Either 5% dextrose or SAMe was injected intraperitoneally 2 h before I/R in steatotic rats (S-D5% or S-SAMe group). Serum liver enzyme concentrations 2 h after reperfusion were significantly lower in the S-SAMe group than in the S-D5% group. The cytosolic and mitochondrial GSH concentrations after I/R were significantly higher in the S-SAMe group than in the S-D5% group (p < 0.05). The cytosolic and mitochondrial oxidized-glutathione/GSH ratios after I/R were significantly greater in the S-D5% group than in the S-SAMe group (p < 0.01). The adenosine triphosphate concentration was higher in the S-SAMe group than in the S-D5% group (p = 0.0515). These results show that hepatocellular and mitochondrial oxidative stress after I/R in the steatotic liver can be reduced by administration of SAMe. The results also show that mitochondrial function and hepatocellular integrity can be restored by administration of SAMe in steatotic rats.

Targeting cholesterol at different levels in the mevalonate pathway protects fatty liver against ischemia–reperfusion injury

“…Consistent with this outcome, previous studies reported the depletion of this pool of GSH during hepatic I/R damage, and its restoration by GSH ethyl ester [37] or SAM [38] protected steatotic livers against I/R damage. Although this concept remains to be tested in human fatty liver, mitochondrial GSH depletion has been shown in nonalcoholic steatohepatitis [39] which is associated with increased free cholesterol accumulation and StAR overexpression [40].…”

Ischemic Preconditioning Increases the Tolerance of Fatty Liver to Hepatic Ischemia-Reperfusion Injury in the Rat

“…16 Strategies focused on the improvement of hepatic microcirculation or the inhibition of oxygen-free radical-mediated injury have resulted in decreased injury after I/R in fatty rats livers but were insufficient to prevent hepatic injury. 15,[17][18][19][20] Multiple mechanisms are thus potentially involved in the impaired tolerance to ischemic injury of steatotic livers, and consequently, various pharmacological strategies may need to be combined to effectively protect the fatty liver. Moreover, the different mechanisms of cell death in fatty versus nonfatty livers, 21 point to the potential differences in the mechanisms involved in hepatic I/R injury in both types of the livers.…”

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

“…During the period or at the end of WI, ATP was low for both steatotic and lean livers [22,43]. However, the recovery of ATP levels in post-IRI steatotic livers were slower [22,43,45], with decreased ATP [22,30,37,39,41,44,49,50] and increased ADP concentrations [27,43], and the net effect of decreased overall energy charge [43] of steatotic livers. Similarly, at the end of cold ischemia, ATP levels showed no difference between steatotic and lean livers [64].…”

“…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]<...>…”

“…Using different substrate/inhibitor protocols, researchers are now able to test the flux through different respiratory complexes within the ETS and estimate respiration efficiencies [89]. Complex I substrates are derived from tricarboxylic acid cycle dehydrogenase reactions and release reduced nicotinamide adenine dinucleotide, while complex II, which is part of the tricarboxylic acid cycle is directly fueled by [40]; b, [40,64]; c, [27]; d, [64]; e, [40,45,64]; f, [27,40,64]; g, [34]; h, [19]; i, [27,38,40,47,64]; j, [24,27]; k, [23,27]; l, [22,43,64]; m, [22,43,45,64]; n, [27,43,65]; o, [22,30,37,39,41,44,49,50,53,57,61,64,66,…”