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.

Toxic effects of environmentally relevant concentrations of naproxen exposure on Daphnia magna including antioxidant system, development, and reproduction.

Naproxen (NPX) is one of common non-prescription non-steroidal anti-inflammatory drugs (NSAIDs) which is widely detected in aquatic environments worldwide due to its high usage and low degradation. NPX exerts anti-inflammatory and analgesic pharmacological effects through the inhibition of prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase (COX). Given its evolutionarily relatively conserved biological functions, the potential toxic effects of NPX on non-target aquatic organisms deserve more attention. However, the ecotoxicological studies of NPX mainly focused on its acute toxic effects under higher concentrations while the chronic toxic effects under realistic concentrations exposure, especially for the underlying molecular mechanisms still remain unclear. In the present study, Daphnia magna, being widely distributed in freshwater aquatic environments, was selected to investigate the toxic effects of environmentally relevant concentrations of NPX via determining the response of the Nrf2/Keap1 signaling pathway-mediated antioxidant system in acute exposure, as well as the changes in life-history traits, such as growth, reproduction, and behavior in chronic exposure. The results showed that the short-term exposure to NPX (24 h and 48 h) suppressed ptgs2 expression while activating Nrf2/Keap1 signaling pathway and its downstream antioxidant genes (ho-1, sod, cat and trxr). However, with prolonged exposure to 96 h, the opposite performance was observed, the accumulation of malondialdehyde (MDA) indicated that D. magna suffered from severe oxidative stress. To maintain homeostasis, the exposed organism may trigger ferroptosis and apoptosis processes with the help of Silent mating type information regulation 2 homologs (SIRTs). The long-term chronic exposure to NPX (21 days) caused toxic effects on D. magna at the individual and population levels, including growth, reproduction and behavior, which may be closely related to the oxidative stress induced by the drug. The present study suggested that more attention should be paid to the ecological risk assessment of NSAIDs including NPX on aquatic non-target organisms.

Hypoxia aggravates the burden of yellowstripe goby (Mugilogobius chulae) under atorvastatin exposure.

In the present study, an estuarine benthic fish, Mugilogobius chulae (M. chulae), was exposed to hypoxia, atorvastatin (ATV), a highly used and widely detected lipid-lowering drug in aquatic environment, and the combination of hypoxia and ATV for 7 days, respectively, so as to address and compare the effects of the combination of hypoxia and ATV exposure on M. chulae. The results showed that lipid metabolism in M. chulae was greatly affected: lipid synthesis was blocked and catabolism was enhanced, exhibiting that lipids content were heavily depleted. The combined exposure of hypoxia and ATV caused oxidative stress and induced massive inflammatory response in the liver of M. chulae. Signaling pathways involving in energy metabolism and redox responses regulated by key factors such as HIF, PPAR, p53 and sirt1 play important regulatory roles in hypoxia-ATV stress. Critically, we found that the response of M. chulae to ATV was more sensitive under hypoxia than normoxia. ATV exposure to aquatic non-target organisms under hypoxic conditions may make a great impact on the detoxification and energy metabolism, especially lipid metabolism, and aggravate the oxidative pressure of the exposed organisms.