Detoxification metabolic pathways and hepatotoxicity mechanisms of B[a]P in reproductive clam Ruditapes philippinarum

Abstract

The liver is a major organ of digestion and detoxification metabolism in animals, and the occurrence of most liver diseases is closely associated with environmental pollution. Besides, liver is a non-reproductive primary target organ regulated by sex steroid hormone signaling. In this study, we elucidated the detoxification metabolism pathways of B[a]P in the clam Ruditapes philippinarum and identified the hepatotoxicity mechanism of B[a]P using technical approaches such as transcriptomics, computer simulation and experimental validation. We found that the AhR signaling pathway and CYP450 family (CYP1A1, CYP2B1, CYP3A4) and FMO in the digestive gland of clam play important roles in the detoxification metabolism of B[a]P, but the performance varied between male and female clams. SOD1 and CAT, GPX, PRDX play antioxidant function but PRDX pathway did not function in females. The level of detoxification metabolism in reproductive clams under B[a]P stress was female < male, oxidative stress was female > male, and oxidative damage was female < male. Cell death (apoptosis, pyroptosis and ferroptosis) was aggravated in the digestive gland of both males and females, with a reduced level of hepatic function health and an increase in the level of inflammatory factors, but males presented a more pronounced tendency toward hepatic fibrosis. In summary, the results of this study enrich the research perspectives on the metabolic pathways of POPs in aquatic invertebrates and lay the foundation for the study of POPs-induced hepatotoxicity, which is of great significance for the conservation of marine biological resources and the monitoring of POPs pollution.