Table 3.

An overview of the literature on the impact of NAC on lipid accumulation, oxidative stress and inflammation in knockout models of NAFLD.

Author, Year	Experimental Model, NAC Dosage, and Intervention Period	Main Findings
Laurent et al., 2004 [65]	Male C57BL/6J obese ob/ob and lean wild-type mice between 8 and 10 weeks of age fed a standard diet were injected with NAC at 150 mg/kg every 3 days for 2 months.	NAC reduced lipoperoxidation and increased the intracellular and the mitochondrial pool of GSH, whereas the other antioxidant molecules tested were ineffective. However, it failed to ameliorate or lower cytochrome C release and caspase-3 activity.
de Oliveira et al., 2006 [67]	NAFLD was induced in ob/ob by MCD diet before oral gavage with SNAC 1.4 μmol/kg) for 4 weeks.	No significant changes in food intake or body weight were observed in comparison to the control group. After SNAC treatment, several genes belonging to oxidative phosphorylation, fatty acid biosynthesis, fatty acid metabolism and glutathione metabolism pathways were downregulated in comparison to the MCD group.
Oliveira et al., 2007 [68]	NAFLD was induced in male ob/ob mice using a MCD diet concomitantly with oral SNAC (1.4 mmol/kg) by gavage daily for 4 weeks.	SNAC markedly reduced liver steatosis, as well as parenchymal inflammation and microsomal triglyceride transfer protein.
de Oliveira et al., 2008 [66]	NAFLD was induced in male ob/ob mice by MCD diet and high-fat diets before the oral administration of SNAC solution (1.4 mg/kg/day) for 4 weeks.	SNAC inhibited the development of NAFLD, leading to a marked decrease in macro and microvacuolar steatosis and hepatic lipid peroxidation in the MCD group. SNAC treatment reversed the development of NAFLD in animals treated for 60 days with MCD and high-fat diets.
Chen et al., 2015 [70]	Polymerase η defiant (pol η−/−) mice fed HFD received NAC (1 mg/mL; wt/vol) or metformin (1.5 mg/mL; wt/vol) in drinking water, from week 8.	NAC and metformin suppressed DNA damage and the metabolic changes induced by a high-fat diet in both WT and pol η−/− mice, suggesting that metabolic abnormalities may be a general response to elevated DNA damage.
Gentric et al., 2015 [9]	Primary hepatocytes from ob/ob mice were treated with 7.5 mM NAC after seeding and during the whole culture time.	NAC treatment impaired the accumulation of ROS as well as that of Gpx3 and Hba1 mRNA, with no impact on cell viability. Moreover, the accumulation of BrdU at 60 h after plating was lower in ob/ob hepatocytes treated with NAC than in untreated cells, showing that treated cells progressed normally through the cell cycle.
Lee et al., 2015 [71]	Primary cultured hepatocytes from superoxide dismutase 1 (Sod1)-deficient and wild-type C57BL/6 mice treated with NAC at 2 mM for 2 h.	NAC was found to be effective in suppressing lipogenesis in the WT cells but not in the Sod1-KO cells.
Preziosi et al., 2017 [72]	Iron overload in liver-specific β-catenin knockout mice. NAC (2 g/kg) was added to drinking water for 3 months.	NAC protected KO +Fe from hepatic steatosis, injury and fibrosis, and prevented activation of AKT, ERK, NF-kB and reappearance of β-catenin.
Kumar et al., 2019 [69]	Primary hepatocytes from augmenter of liver regeneration (ALR) (ALR-L-knockout (KO)) mice pre-incubated with 10 mM NAC for 30 min.	NAC and recombinant ALR (rALR) both inhibited ALR depletion-induced miR-540 expression and lipid accumulation in hepatocytes.
Shin et al., 2019 [73]	Male catalase knockout (CKO) mice were fed an HFD for 6 weeks. NAC (60 mg/kg/day) or melatonin (500 μg/kg/day) were dissolved in saline solution and injected intraperitoneally for 6 weeks.	Co-treatment with NAC and melatonin suppressed fatty liver development and improved hepatic mitochondrial function.
Mai et al., 2020 [63]	NAC (10 μM) was applied in combination with MCD/lipopolysaccharide (LPS) or palmitate for 24 h in AML12 (alpha mouse liver 12) cells.	Thioredoxin interacting protein, Nod-like receptor family pyrin domain containing 3 (NLRP3), pro-caspase 1, and caspase-1 activity were suppressed by NAC.