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While the toxic ramifications of antibiotics and heavy metals have been extensively studied individually, their co\u2010toxicity on aquatic piscine models and the associated cellular stress responses remain poorly understood. The research focuses on understanding the mechanisms of stress and simultaneous toxicity in this specific scenario. The study revealed elevated levels of cellular ROS, MDA, and GSH, along with increased CAT enzyme activity in all treated groups, indicating oxidative stress. Histological damages, including increased numbers of goblet cells and necrotic spots, further confirmed oxidative injury. Gene expression analysis showed enhancement of stress\u2010responsive genes such as <jats:italic>nrf2<\/jats:italic>, <jats:italic>GPx\u20101<\/jats:italic>, <jats:italic>hsp70<\/jats:italic>, <jats:italic>keap1<\/jats:italic>, <jats:italic>nqo1<\/jats:italic>, <jats:italic>Cyp 1a<\/jats:italic>, <jats:italic>ucp2<\/jats:italic>, <jats:italic>Cu\/Zn\u2010SOD<\/jats:italic>, and <jats:italic>Mn\u2010SOD<\/jats:italic>, aligning with the observed biochemical changes. The translocation and heightened expression of Nrf2 in the nucleus were notable across all treatments. Furthermore, the combined effects of AMX, As, and F were more pronounced compared to other combinations, while exposure to AMX alone had the least impact. These findings underscore the role of the Nrf2\u2010Keap1\u2010ARE pathway in mediating the observed responses and highlight the synergistic toxicity of AMX, As, and F in the environment, posing a significant threat to both ecosystems and human health.<\/jats:p>","DOI":"10.1002\/jat.4842","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T20:34:59Z","timestamp":1750970099000},"page":"2278-2288","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Oxidative Stress in Zebrafish Gut Induced by Individual and Combined Exposure to Amoxicillin, Arsenic and Fluoride: Engagement of Nrf2\u2010Keap1\u2010ARE Pathway"],"prefix":"10.1002","volume":"45","author":[{"given":"Sunanda","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Department of Zoology Visva\u2010Bharati  Santiniketan West Bengal 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