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However, their interactive effects on fish are unclear. Aiming to determine their interactive effects, silver carp (Hypophthalmichthys molitrix) were exposed to ammonia, nitrite or ammonia + nitrite for 72 h. Silver carp exhibited pathological damage in the liver and spleen and significant increases in MDA, SOD and CAT in the liver and plasma after ammonia or nitrite exposure. Thus, ammonia and nitrite caused significant histology damage through inducing oxidative stress, and the antioxidative response of SOD\u2212CAT was initiated by silver carp to defend them. A transcriptomic analysis suggested that disruptions in immune responses and metabolism were the main toxic effects caused by ammonia and nitrite. Specifically, nitrite decreased splenic TNF-\u03b1 and IL-1\u03b2 but increased splenic C4. Ammonia decreased splenic TNF-\u03b1 and C4 but increased splenic IL-1\u03b2. We noted significant interactions between ammonia and nitrite, and the pathological changes and IBR in the co-exposure groups were less severe than those in the single-factor exposure groups, indicating that ammonia and nitrite have an antagonistic effect. Significant decreases in plasmatic ammonia and NO2\u2212+NO3\u2212 were induced by nitrite and ammonia, respectively. Moreover, the plasmatic glutamine, urea-N, and glutamine synthetase and glutamate dehydrogenase activities increased significantly under ammonia and nitrite exposure, while T-NOS decreased significantly. These results suggest an antagonistic interaction between ammonia and nitrite in silver carp, possibly resulting from competitive bioaccumulation. Consequently, the simultaneous monitoring and control of both ammonia and nitrite concentrations are essential to mitigate their compounded toxic effects, which might be exacerbated under isolated exposure conditions.<\/jats:p>","DOI":"10.3390\/antiox14040453","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T12:49:01Z","timestamp":1744289341000},"page":"453","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Competitive Bio-Accumulation Between Ammonia and Nitrite Results in Their Antagonistic Toxicity to Hypophthalmichthys molitrix: Antioxidant and Immune Responses and Metabolic Detoxification Evidence"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1512-0975","authenticated-orcid":false,"given":"Honghui","family":"Guo","sequence":"first","affiliation":[{"name":"Yangtze River Fisheries Research Institute, Chinese Academy of Fisheries, Wuhan 430223, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Li","sequence":"additional","affiliation":[{"name":"Yangtze River Fisheries Research Institute, Chinese Academy of Fisheries, Wuhan 430223, China"},{"name":"College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Ge","sequence":"additional","affiliation":[{"name":"Yangtze River Fisheries Research Institute, Chinese Academy of Fisheries, Wuhan 430223, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Sha","sequence":"additional","affiliation":[{"name":"Yangtze River Fisheries Research Institute, Chinese Academy of Fisheries, Wuhan 430223, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangzhong","family":"Luo","sequence":"additional","affiliation":[{"name":"Yangtze River Fisheries Research Institute, Chinese Academy of Fisheries, Wuhan 430223, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiwei","family":"Zou","sequence":"additional","affiliation":[{"name":"Yangtze River Fisheries Research Institute, Chinese Academy of Fisheries, Wuhan 430223, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5840-5006","authenticated-orcid":false,"given":"Hongwei","family":"Liang","sequence":"additional","affiliation":[{"name":"Yangtze River Fisheries Research Institute, Chinese Academy of Fisheries, Wuhan 430223, China"},{"name":"College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1890\/06-1293.1","article-title":"Ammonia modeling for assessing potential toxicity to fish species in the Rio Grande, 1989\u20132002","volume":"17","author":"Passell","year":"2007","journal-title":"Ecol. 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