Mustafa Öz, Enes Üstüner
The rapid expansion of global aquaculture has increased fish exposure to multiple xenobiotics, including agricultural chemicals, industrial pollutants, and emerging contaminants such as microplastics. Although numerous studies have examined individual toxicants, a critical knowledge gap remains regarding integrative, nutrition-based detoxification strategies that simultaneously mitigate oxidative stress, enhance endogenous detoxification pathways, and reduce dependence on chemical therapeutics. This review addresses the question of how bioactive feed additives can be strategically used to support physiological detoxification mechanisms in fish exposed to complex xenobiotic mixtures. The review synthesizes current evidence on phytogenic compounds, functional amino acids, trace elements, and advanced delivery systems that activate antioxidant defense systems, phase I and phase II detoxification enzymes, and cellular repair processes. Particular emphasis is placed on molecular pathways such as nuclear factor erythroid 2-related factor 2 signaling, species-specific detoxification capacity, and the interaction between nutrition, gut microbiota, and immune function. Comparative evidence across major aquaculture species demonstrates that nutritional detoxification strategies can improve resilience to oxidative damage while contributing to reduced antibiotic use and improved product safety. By integrating mechanistic insights with One Health and sustainability perspectives, this review highlights nutritional detoxification as a scalable and environmentally responsible approach for managing xenobiotic stress in modern aquaculture systems.