S-Nitroso-N-Acetylcysteine Ameliorates Ischemia-Reperfusion Injury In The Steatotic Liver

Abstract

BACKGROUND:Steatosis is currently the most common chronic liver disease and it can aggravate ischemia-reperfusion (IR) lesions. We hypothesized that S-nitroso-N-acetylcysteine (SNAC), an NO donor component, can ameliorate cell damage from IR injury. In this paper, we report the effect of SNAC on liver IR in rats with normal livers compared to those with steatotic livers.METHODS:Thirty-four rats were divided into five groups: I (n=8), IR in normal liver; II (n=8), IR in normal liver with SNAC; III (n=9), IR in steatotic liver; IV (n=9), IR in steatotic liver with SNAC; and V (n=10), SHAN. Liver steatosis was achieved by administration of a protein-free diet. A SNAC solution was infused intraperitoneally for one hour, beginning 30 min. after partial (70%) liver ischemia. The volume of solution infused was 1 ml/100 g body weight. The animals were sacrificed four hours after reperfusion, and the liver and lung were removed for analysis. We assessed hepatic histology, mitochondrial respiration, oxidative stress (MDA), and pulmonary myeloperoxidase.RESULTS:All groups showed significant alterations compared with the group that received SHAN. The results from the steatotic SNAC group revealed a significant improvement in liver mitochondrial respiration and oxidative stress compared to the steatotic group without SNAC. No difference in myeloperoxidase was observed. Histological analysis revealed no difference between the non-steatotic groups. However, the SNAC groups showed less intraparenchymal hemorrhage than groups without SNAC (p=0.02).CONCLUSION:This study suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver.

Adenosine receptors: regulatory players in the preservation of mitochondrial function induced by ischemic preconditioning of rat liver

“…Furthermore, IPC decreases liver injury after both warm and cold I/R [2,4,9,10]. Several mechanisms have been proposed for protection by IPC, including activation of adenosine receptors [11][12][13][14], increased nitric oxide production [15], activation of protein kinase C [16], up-regulation of heat shock proteins, and increased antioxidant capacity [17,18]. Probably, the process better established to be associated with decrease tolerance to I/R injury is the inability to restore energetic balance following I/R [1,19,20].…”

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

“…Twenty-seven studies utilizing the thiobarbituric acid reactive substances assay showed significantly increased levels of MDA in steatotic livers post-IRI [20,21,23,25,28,32,34,38,40,44,46,48,52,54,55,57,[61][62][63]69,[71][72][73][75][76][77][78] while Nakano and colleagues [17] reported similar levels of perfusate MDA to that seen from lean livers. Serviddio et al [47] also reported a significant increase in mitochondrial 4-hydroxy-2-nonenal-protein adducts post-IRI in steatotic livers.…”

“…Interestingly, one study noted a downward trend in phosphate/oxygen ratio in post-IRI steatotic livers [34], but there was no difference in phosphate/oxygen ratio between the two groups of livers pre-or post-IRI [27,40]. There was also no difference in FCCP-induced (a mitochondrial respiratory uncoupler) respiration post-IRI indicating no difference in maximal ETS capacity between the liver types [27].…”

“…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,…”