NAC treatment ameliorates a subset of abnormal phenotypes in NPC1ASO liver. (A) NAC reduced the significantly increased liver/body weight ratio in NPC1ASO mice to that of CTLASO mice. (B and C) NAC reduced the significantly elevated plasma levels of ALT and AST in NPC1ASO mice to CTLASO levels. (D) NPC1 protein remained undetectable in NAC-treated NPC1ASO mice, demonstrating that NAC treatment did not interfere with ASO-induced knockdown of NPC1. (E) Without NAC treatment (left two bars), NPC1ASO mice showed a significantly lower GSH level compared to CTLASO mice, indicative of oxidative stress. NAC treatment of NPC1ASO mice increased the GSH level in liver, but this increase was not statistically significant. (F) Comparison of histological sections from untreated (left) and NAC-treated (right) NPC1ASO mice showed that NAC treatment did not reduce the activated macrophages and histiocytosis in NPC1ASO liver. All mice received ASO treatment for 4 weeks, and NAC-treated mice concurrently received NAC for 4 weeks. Data analyzed by two-way ANOVA with post-tests; column lettering (a, b) indicates significance (P < 0.05), as described in Figure 1. Scale bar in F = 5 µm. n = 4–5 for each treatment group.