Albicanol modulates oxidative stress and the p53 axis to suppress profenofos induced genotoxicity in grass carp hepatocytes

Abstract

The organophosphorus pesticide profenofos (PFF) is widely used as an environmental contaminant, and it can remain in water bodies causing serious harm to aquatic organisms. Albicanol is a sesquiterpenoid with potent antioxidant and antagonistic activities against heavy metal toxicity. However, the mechanism of PFF induced genotoxicity in fish hepatocytes and the role Albicanol can play in this process are unknown. In this study, the model was established by treating grass carp hepatocytes with PFF (150 μM) and/or Albicanol (5 × 10^-5 μg mL^-1) for 24 h. The results showed that PFF exposure arrested L8824 cells in the G1-S phase. PFF caused the increase of MDA level in L8824 cells, while the decrease of SOD, CAT and T-AOC levels caused oxidative stress. Elevated levels of γH2AX, tail moment, tail length, % DNA and 8-OHdG indicated that PFF caused DNA damage in L8824 cells. PFF inhibited the expression levels of cell cycle related regulatory genes (cyclin A, cyclin D, cyclin E, CDK2 and CDK4) by upregulating p53/p21 genes and activating the p53 signaling pathway. Albicanol was used to significantly reduce the above effects caused by PFF exposure on hepatocytes in grass carp. Albicanol could reduce the increase in the proportion of cells in the G1-S phase caused by PFF. In summary, Albicanol could inhibit the genotoxicity of L8824 cells resulted from PFF exposure by decreasing oxidative stress and the p53 pathway.

Keywords: Albicanol; DNA Damage; L8824 cells; P53 pathway; Profenofos.