Oxytetracycline-induced oxidative liver damage by disturbed mitochondrial dynamics and impaired enzyme antioxidants in largemouth bass (Micropterus salmoides)

Aquat Toxicol. 2023 Aug:261:106616. doi: 10.1016/j.aquatox.2023.106616. Epub 2023 Jun 17.

Abstract

Oxytetracycline (OTC), a commonly used tetracycline antibiotic in aquaculture, has been found to cause significant damage to the liver of largemouth bass (Micropterus salmoides). This study revealed that OTC can lead to severe histopathological damage, structural changes at the cellular level, and increased levels of reactive oxygen species (ROS) in M. salmoides. Meanwhile, OTC impairs the activities of antioxidant enzyme (such as T-SOD, CAT, GST, GR) by suppressing the activation of MAPK/Nrf2 pathway. OTC disrupts mitochondrial dynamics and mitophagy through via PINK1/Parkin pathway. The accumulation of damaged mitochondria, combined with the inhibition of the antioxidant enzyme system, contributes to elevated ROS levels and oxidative liver damage in M. salmoides. Further investigations demonstrated that an enzyme-treated soy protein (ETSP) dietary supplement can help maintain mitochondrial dynamic balance by inhibiting the PINK1/Parkin pathway and activate the MAPK/Nrf2 pathway to counteract oxidative damage. In summary, these findings highlight that exposure to OTC disrupts mitochondrial dynamics and inhibits the antioxidant enzyme system, ultimately exacerbating oxidative liver damage in M. salmoides. We propose the use of a dietary supplement as a preventive measure against OTC-related side effects, providing valuable insights into the mechanisms of antibiotic toxicity in aquatic environments.

Keywords: Enzyme-treated soy protein; MAPK/Nrf2 pathway; Mitochondrial damage; PINK1/Parkin pathway.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Antioxidants / metabolism
  • Bass* / metabolism
  • Liver
  • Mitochondrial Dynamics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress
  • Oxytetracycline* / toxicity
  • Protein Kinases / metabolism
  • Protein Kinases / pharmacology
  • Reactive Oxygen Species / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitin-Protein Ligases / pharmacology
  • Water Pollutants, Chemical* / toxicity

Substances

  • Antioxidants
  • Oxytetracycline
  • Reactive Oxygen Species
  • NF-E2-Related Factor 2
  • Water Pollutants, Chemical
  • Anti-Bacterial Agents
  • Ubiquitin-Protein Ligases
  • Protein Kinases