Albicanol antagonizes PFF-induced mitochondrial damage and reduces inflammatory factors by regulating innate immunity.

ABSTRACT

As an environmental pollutant, profenofos (PFF) can seriously endanger human health through the food chain. Albicanol is a sesquiterpene compound with antioxidant, anti-inflammatory, and anti-aging properties. Previous studies have shown that Albicanol can antagonize apoptosis and genotoxicity caused by PFF exposure. However, the toxicity mechanism of PFF regulating hepatocyte immune function, apoptosis, and programmed necrosis and the role of Albicanol in this process have not been reported yet. In this study, grass carp hepatocytes (L8824) were treated with PFF (200 µM) or combined with Albicanol (5 ×10-5 µg mL-1) for 24 h to establish an experimental model. The results of JC-1 probe staining and Fluo-3 AM probe staining showed increased free calcium ions and decreased mitochondrial membrane potential in L8824 cells after PFF exposure, suggesting that PFF exposure may lead to mitochondrial damage. Real-time quantitative PCR and Western blot results showed that PFF exposure could increase the transcription of innate immunity-related factors (C3, Pardaxin 1, Hepcidin, INF-γ, IL-8, and IL-1ß) in L8824 cells. PFF up-regulated the TNF/NF-κB signaling pathway and the expression of caspase-3, caspase-9, Bax, MLKL, RIPK1, and RIPK3 and down-regulated the expression of Caspase-8 and Bcl-2. Albicanol can antagonize the above-mentioned effects caused by PFF exposure. In conclusion, Albicanol antagonized the mitochondrial damage, apoptosis, and necroptosis of grass carp hepatocytes caused by PFF exposure by inhibiting the TNF/NF-κB pathway in innate immunity.