Figure 5.

The impact of bucillamine on NASH, DNA damage, cellular proliferation and HCC. Dietary supplementation with bucillamine in ALIOS fed C3H/He mice had no impact on steatosis or lobular inflammation, although a cardinal feature of NASH—hepatocyte ballooning—was abrogated, with a corresponding reduction in the NAS score, alongside a significant reduction in fibrosis stage (A) and Sirius Red quantification (B). Of the ancillary features of NASH, Mallory-Denk bodies (MDB) were reduced, as was pericellular fibrosis (PCF), with no changes in the presence of lipogranulomas (LG), microvesicular steatosis (MVS), megamitochondria (MM), portal tract inflammation (PTI), pigmented Kupffer (PK) cells, apoptotic bodies (AB) or portal tract fibrosis (PTF) (C). Despite reduced severity of NASH and fibrosis, there was no impact tumour development or size (C). DNA damage H2AX foci were diminished, although the hepatocyte proliferation biomarker Ki67 was not (E). Quantification at 24 weeks of age confirmed a significant increase in Ki67 assessed proliferation in ALIOS fed mice, further increased at 48 weeks. Induction of H2AX was more dramatic in ALIOS fed mice, but only at 48 weeks. Categorical data statistical differences determined by Chi Square tests; scale data by Mann Whitney Tests (ns-not significant, * p < 0.05, ** p < 0.01, *** p < 0.001).