Integrated metabolomics and transcriptomics analyses for understanding the mechanism underlying amantadine-induced toxicity in Laminaria japonica

Abstract

The antiviral agent, amantadine, is widely present in marine ecosystems and poses a significant threat to marine organisms. However, studies on the toxicity of amantadine across the full life cycle of the brown alga Laminaria japonica, particularly during the microscopic gametophyte stage, remain lacking. A comprehensive approach combing biochemical analyses and multi-omics techniques was employed to investigate the mechanisms underlying amantadine-induced toxicity in L. japonica gametophytes. The development rate of algal cells was less than 3 % from 10³ to 10⁷ ng/L of amantadine. In total, 1049 differentially expressed genes and 215–231 differential metabolites were detected, with the majority involved in amino acid, lipid, and carbohydrate metabolism. Integrated analysis showed that alginate biosynthesis and glycerophospholipid metabolism were affected, suggesting damage to the cell wall and membrane structure. Key genes (e.g., SOD2) and metabolites (e.g., arachidonic acid and α-linolenic acid), associated with the antioxidant system and arachidonic acid metabolism, were identified, leading to oxidative stress in the algae. Furthermore, the downregulation of genes and metabolites involved in porphyrin metabolism, photosynthesis, carbon fixation, glycolysis, and the pentose phosphate pathway may inhibit ATP supply and NADPH generation, negatively affecting metabolic processes and inhibiting algal cell growth. In contrast to disrupting protein synthesis in juvenile sporophytes, amantadine primarily interferes with photosynthesis and carbohydrate metabolism in gametophytes. These findings offer new insights into the mechanisms by which amantadine impedes the growth and metabolism of algae throughout their life cycle in aquatic ecosystems.