A: Flutamide treatment resulted in a marginal increase in the number and area of glutathione S-transferase placental form (GST-P)-positive foci, indicating preneoplastic lesions. Studies also found that flutamide counteracted HFD-induced mitophagy inhibition, which could potentially contribute to the maintenance and progression of these lesions. This suggests that flutamide may enhance the risk of hepatocarcinogenesis by affecting mitophagy and promoting the formation of preneoplastic lesions.

A: Flutamide treatment led to significant changes in lipid metabolism-related genes, including increased expression of Abca1 and Srebf2 in the HFD + FL group. Additionally, flutamide induced oxidative stress, as evidenced by increased expression of the antioxidant enzyme Gpx2. These findings suggest that flutamide can alter lipid metabolism and induce oxidative stress, which may contribute to the progression of NAFLD and hepatocarcinogenesis.

A: A study found that flutamide significantly increased the expression of autophagy-related genes such as Atg5, Atg7, Lamp1, Lamp2, and Lc3 in the HFD + FL group compared to the HFD group alone. Additionally, flutamide increased the expression of mitophagy-related genes like Parkin and Ambra1, indicating an induction of mitophagy. This suggests that flutamide can modulate autophagy and mitophagy pathways, potentially contributing to its hepatocarcinogenic effects.

A: Flutamide exacerbates HFD-induced steatosis and marginally increases preneoplastic lesions in rats. It counteracts HFD-mediated mitophagy inhibition, as indicated by increased LC3 and decreased AMBRA1 levels in background hepatocytes. This suggests that FL-induced mitophagy induction relies on Parkin expression and may potentially exacerbate NAFLD-associated hepatocarcinogenesis by affecting mitophagy.