Acetylcysteine Treatment for Non–Acetaminophen-Induced Acute Liver Failure

Abstract

Intravenous acetylcysteine should not be used routinely for treatment of non-acetaminophen-induced ALF. Further large-scale studies are needed to evaluate clinical outcomes.

Metabolic insights into the hepatoprotective role of N-acetylcysteine in mouse liver

“…27,28 Labeling of Metabolites with 13 C. [U- 13 C]glucose allows determination of metabolic pathways used to synthesize downstream compounds. [13][14][15][16][17]27 Briefly, via glycolysis, 1 molecule [U- 13 [1,2,[3][4][5][6][7][8][9][10][11][12][13] C]oxaloacetate, which condenses with acetyl-CoA into citrate. Glucose flux through these 2 pathways can be quantified from 13 C-NMR spectra from the 13 C-labeling pattern in glutamate (Glu) synthesized from the TCA cycle intermediate ␣-ketoglutarate.…”

“…After treatment with NAC, the relative de novo synthesis of GSH via PC (fractional enrichment in [2,3-13 C]GSH) decreased from 1.98% Ϯ 0.30% to 0.87% Ϯ 0.11% at a 300-mg/kg dose (P Ͻ .05; Fig. 4 [4,[5][6][7][8][9][10][11][12][13] C]Glu is a measure of carbon flux through PDH (Supplemental Fig. 1).…”

“…1). [13][14][15][16][17]27 NAC (300 mg/kg) caused increased flux through PDH (increased fractional 13 C-enrichment in [4,[5][6][7][8][9][10][11][12][13] C]Glu from 2.08% Ϯ 0.26% to 4.00 Ϯ 0.44%; Fig. 5).…”

“…5). Despite this augmented flux, the de novo synthesis of GSH via PDH only rose (but less than for Glu) with the 150 mg/kg NAC dose (increased fractional enrichment in [4,[5][6][7][8][9][10][11][12][13] C]GSH from 1.48% Ϯ 0.14% to 1.87% Ϯ 0.20%; P Ͻ .05), did not change significantly with 300 mg/kg NAC, and decreased at higher NAC doses to 0.61% Ϯ 0.10% (P Ͻ .05).…”

“…Furthermore, because NAC is recognized as an antioxidant, it might be useful in the setting of liver injuries different from those caused by acetaminophen intoxication. [6][7][8][9][10][11] NAC has also been reported to improve oxygen delivery, 4 to increase systemic oxygen consumption, 12 and to have beneficial effects on liver blood flow and function. 6,8,10 Because liver oxygen consumption is coupled with aerobic oxidation of energy substrates in the mitochondrial tricarboxylic acid (TCA) cycle, we hypothesize that NAC might improve hepatocellular energy metabolism.…”