Multi-omics analysis reveals the toxic mechanism of tributyltin exposure causing digestive gland oxidative stress in cuttlefish (Sepia pharaonis)

Tributyltin (TBT) is known for its environmental persistence and high toxicity, posing a significant threat to benthic aquatic organisms in coastal zones. The present study employed physiological, histological, and multiomics techniques to investigate the toxic effects of TBT exposure and the detoxification mechanisms in Sepia pharaonis. The results revealed that TBT exposure resulted in reduced growth performance, elevated activity of the antioxidant enzyme system, and pronounced histopathological alterations in the digestive glands, suggesting substantial oxidative stress within these tissues. Transcriptome analysis indicated that differentially expressed genes were significantly enriched in pathways related to reactive oxygen species (ROS) metabolism, oxidative stress, the mitochondrial respiratory chain, antioxidant activity, and stress responses. Furthermore, levels of metabolites involved in ROS scavenging-including oxidized glutathione, L-arginine, L-glutamate, gamma-glutamyl-Lalanine, and L-glycine-were markedly elevated, reflecting the organism's response to reduce the excess ROS induced by TBT stress. Additionally, the integrated analysis of transcriptome and metabolome data indicated that the cuttlefish could effectively counteract TBT-induced oxidative stress via its antioxidant enzyme system. However, exposure to high concentrations of TBT prompted a shift from reliance on the antioxidant enzyme system to the activation of detoxification defense mechanisms, with a pronounced effect on glutathione metabolism and arginine biosynthesis. In conclusion, our findings enhance the understanding of S. pharaonis's adaptability to TBT-stressed environments and offer new insights into the molecular mechanisms underlying TBT-induced detoxification.