Integrative Inducer Intervention and Transcriptomic Analyses Reveal the Metabolism of Paralytic Shellfish Toxins in Azumapecten farreri.

Paralytic shellfish toxins (PSTs) are widely distributed neurotoxins, and the PST metabolic detoxification mechanism in bivalves has received increasing attention. To reveal the effect of phase I (cytochrome P450)-II (GST)-III (ABC transport) metabolic systems on the PST metabolism in Azumapecten farreri, this study amplified stress on the target systems using rifampicin, dl-α-tocopherol, and colchicine; measured PST levels; and conducted transcriptomic analyses. The highest toxin content reached 1623.48 µg STX eq/kg in the hepatopancreas and only 8.8% of that in the gills. Inducer intervention significantly decreased hepatopancreatic PST accumulation. The proportional reductions in the rifampicin-, dl-α-tocopherol-, and colchicine-induced groups were 55.3%, 50.4%, and 36.1%, respectively. Transcriptome analysis showed that 11 modules were significantly correlated with PST metabolism (six positive/five negative), with phase I CYP450 and phase II glutathione metabolism significantly enriched in negatively correlated pathways. Twenty-three phase I-II-III core genes were further validated using qRT-PCR and correlated with PST metabolism, revealing that CYP46A1, CYP4F6, GSTM1, and ABCF2 were significantly correlated, while CYP4F11 and ABCB1 were indirectly correlated. In conclusion, phase I-II-III detoxification enzyme systems jointly participate in the metabolic detoxification of PSTs in A. farreri. This study provides key data support to profoundly elucidate the PST metabolic detoxification mechanism in bivalves.

Coordination regulation of enhanced performance reveals the tolerance mechanism of Chlamys farreri to azaspiracid toxicity.

Azaspiracids (AZAs) are lipid biotoxins produced by the marine dinoflagellates Azadinium and Amphidoma spp. that can accumulate in shellfish and cause food poisoning in humans. However, the mechanisms underlying the tolerance of shellfish to high levels of such toxins remain poorly understood. This study investigated the combined effects of detoxification metabolism and stress-related responses in scallops Chlamys farreri exposed to AZA. Scallops accumulated a maximum of 361.81 µg AZA1 eq/kg and 41.6 % AZA residue remained after 21 days of exposure. A range of AZA2 metabolites, including AZA19, AZA11, and AZA23, and trace levels of AZA2-GST, were detected. Total hemocyte counts significantly increased and ROS levels remained consistently high until gradually decreasing. Immune system activation mediated mitochondrial dysfunction and severe energy deficiency. DEGs increased over time, with key genes CYP2J6 and GPX6 contributing to AZA metabolism. These transcriptome and metabolic results identify the regulation of energy metabolism pathways, including inhibition of the TCA cycle and activation of carbohydrates, amino acids, and lipids. AZA also induced autophagy through the MAPK-AMPK signaling pathways, and primary inhibited PI3K/AKT to decrease mTOR pathway expression. Our results provide additional insights into the resistance of C. farreri to AZA, characterized by re-establishing redox homeostasis toward a more oxidative state.