Aspirin exposure coupled with hypoxia interferes energy metabolism, antioxidant and autophagic processes and causes liver injury in estuarine goby Mugilogobius chulae.

ABSTRACT

Toxicity assessments of pollutants often overlook the impact of environmental factors like hypoxia, which can alter chemical toxicity with unexpected consequences. In this study, Mugilogobius chulae, an estuarine fish, was used to investigate the effects of hypoxia (H), aspirin (ASA), and their combination (H_ASA) exposure over 24, 72, and 168 h. We employed RNA-seq analysis, expression of key gene expression profiling, enzymatic activity assays, and histopathological and ultrastructural examinations of liver tissue to explore the effects and mechanisms of ASA-coupled hypoxia exposure in fish. Results showed that glycolysis was inhibited, and lipolysis was enhanced in ASA/H_ASA groups. The PPAR signaling pathway was activated, increasing fatty acid ß-oxidation and lipophagy to mitigate energy crisis. Both ASA and H_ASA exposures induced p53 expression and inhibited the TOR pathway to combat environmental stress. However, a greater energy demand and heightened sensitivity to ASA were observed in H_ASA compared to ASA exposure. Disruptions in energy and detoxification pathways led to increased stress responses, including enhanced antioxidant activities, autophagy, and apoptotic events, as observed in organelle structures. Overall, sub-chronic H_ASA exposure caused liver injury in M. chulae by affecting energy metabolism, antioxidant regulation, and autophagy processes. This study highlights the influence of hypoxia on ASA toxicity in fish, providing valuable insights for ecological risk assessment of NSAIDs.