Differential Cell Death Pathways Induced by Oxidative Stress in Multi-Organs of Amur Grayling (Thymallus grubii) Under Gradient Ammonia Stress

Ammonia nitrogen is a common contaminant in aquatic environments, and its potential toxicity to organisms has attracted extensive attention. However, few studies have comprehensively evaluated the negative impacts of ammonia stress on cold-water fish. In this study, liver, gill, and intestine specimens of Amur grayling (<i>Thymallus grubii</i>) from three treatment groups (control (0 mg/L), low ammonia (43.683 mg/L), and high ammonia (436.8 mg/L)), were collected for histological observation, biochemical examination, and transcriptomic, metabolomic, and intestinal microbiome analysis. Our results showed that excessive ammonia nitrogen blocked the normal immune function and compromised the integrity of liver and gill tissues through oxidative stress-mediated differential cell death pathways. Meanwhile, the multi-omics analysis revealed that ammonia exposure predominantly altered the carbohydrate, lipid, and amino acid metabolism modes. In addition, it was also demonstrated that ammonia nitrogen stress affected the composition of intestinal microbiota taxa. This study provides insights into the potential risks and hazards of ammonia stress on cold fish in natural waters and provides a reference for the environment control of the water quality in aquaculture.