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

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.

Atorvastatin causes developmental and behavioral toxicity in yellowstripe goby (Mugilogobius chulae) embryos/larvae via disrupting lipid metabolism and autophagy processes.

Atorvastatin (ATV) is one of the most commonly prescribed lipid-lowering drugs detected frequently in the environment due to its high use and low degradation rate. However, the toxic effects of residual ATV in the aquatic environment on non-target organisms and its toxic mechanisms are still largely unknown. In the present study, embryos of a native estuarine benthic fish, Mugilogobius chulae, were employed to investigate the developmental and behavioral toxic effects of ATV including environmentally relevant concentrations. The aim of this study was to provide a scientific basis for ecological risk assessment of ATV in the aquatic environment by investigating the changes of biological endpoints at multiple levels in M. chulae embryos/larvae. The results showed that ATV had significantly lethal and teratogenic effects on M. chulae embryos/larvae and caused abnormal changes in developmental parameters including hatch rate, body length, heart rate, and spontaneous movement. ATV exposure caused oxidative stress in M. chulae embryos/larvae subsequently inhibited autophagy and activated apoptosis, leading to abnormal developmental processes and behavioral changes in M. chulae embryos/larvae. The disruptions of lipid metabolism, autophagy, and apoptosis in M. chulae embryos/larvae caused by ATV exposure may pose a potential ecological risk at the population level.

Response of lipid metabolism, energy supply, and cell fate in yellowstripe goby (Mugilogobius chulae) exposed to environmentally relevant concentrations atorvastatin.

The usage of typical pharmaceuticals and personal care products (PPCPs) such as cardiovascular and lipid-modulating drugs in clinical care accounts for the largest share of pharmaceutical consumption in most countries. Atorvastatin (ATV), one of the most commonly used lipid-lowering drugs, is frequently detected with lower concentrations in aquatic environments owing to its wide application, low removal, and degradation rates. However, the adverse effects of ATV on non-target aquatic organisms, especially the molecular mechanisms behind the toxic effects, still remain unclear. Therefore, this study investigated the potentially toxic effects of ATV exposure (including environmental concentrations) on yellowstripe goby (Mugilogobius chulae) and addressed the multi-dimensional responses. The results showed that ATV caused typical hepatotoxicity to M. chulae. ATV interfered with lipid metabolism by blocking fatty acid ß-oxidation and led to the over-consumption of lipids. Thus, the exposed organism was obliged to alter the energy supply patterns and substrates utilization pathways to keep the normal energy supply. In addition, the higher concentration of ATV exposure caused oxidative stress to the organism. Subsequently, M. chulae triggered the autophagy and apoptosis processes with the help of key stress-related transcriptional regulators FOXOs and Sestrins to degrade the damaged organelles and proteins to maintain intracellular homeostasis.