Study on toxicity responses in Xenopus tropicalis long-term exposure to norfloxacin, oxytetracycline and arsenic

The presence of residues of antibiotics and heavy metals in the global aquatic environment is a widespread potential environmental risk. Here, we studied their effect on Xenopus tropicalis by analysing the hepatotoxic effects of norfloxacin (NOR), oxytetracycline (OTC), and arsenic (As) on its histology, lipidomics, proteases, and cytokines. The results showed that development was inhibited, and additional vacuolation, sinusoids, pyknosis, nuclei, cell lysis, and leukocyte infiltration were observed in the liver after 72 days of exposure to NOR (0.1-4.0 mg L^-1), OTC (0.1-4.0 mg L^-1), and/or As (0.3-3.5 μg L^-1). In addition, the size and number of lipid droplets increased with the superposition of drugs, disrupting lipid droplet homeostasis. Lipidomics proved that the intensity of lipid responses related to lipid metabolism was disrupted, especially for CerP and TAG. In addition, the lipotoxicity induced by joint exposure was more potent than that induced by a single exposure. Compared with the controls, the ROS levels in the liver were 7.21%-37.18% greater, which promoted oxidative stress damage. By revealing the underlying mechanisms involved, we found that the liver can resist oxidative stress and lipid peroxidation by regulating the expression of multiple cytokines. Our study provides new insights into the hepatotoxicity and underlying mechanisms in aquatic amphibians caused by long-term exposure to low concentrations of NOR, OTC, and/or As.