Deacetyl epoxyazadiradione ameliorates BPA-induced neurotoxicity by mitigating ROS and inflammatory markers in N9 cells and zebrafish larvae

Comp Biochem Physiol C Toxicol Pharmacol. 2023 Sep:271:109692. doi: 10.1016/j.cbpc.2023.109692. Epub 2023 Jun 30.

Abstract

Bisphenol A (BPA) leaches from plastic products have become a major inevitable concern among the research society. Human exposure to BPA leads to deleterious effects on multiple organs by the induced hyper inflammatory and oxidative stress responses. Due to the compromised antioxidant mechanism, the brain environment was highly susceptible and required special concern to ameliorate the effects of BPA. Hence, this study investigates the potential of neem-derived semi natural deacetyl epoxyazadiradione (DEA) against the oxidative stress and inflammatory response induced by BPA exposure in N9 cells and zebrafish larvae. The results from the in vitro analyses showed a decrease in cell viability in the MTT assay and a decline in mitochondrial damage in BPA-exposed N9 cells. Further in vivo, results revealed that pre-treatment of DEA to zebrafish larvae has significantly reduced the level of superoxide anion and increased the production of antioxidant enzymes such as SOD, CAT, GST, GPx and GR. We also found a significant decrease in the production of nitric oxide (p < 0.0001) and iNOS gene expression at 150 μM concentration. Further, DEA pre-treatment improved the behaviour of zebrafish larvae by ameliorating the production of the AChE enzyme. In conclusion, DEA protected zebrafish larvae from BPA toxicity by ameliorating oxidative stress and inflammatory responses.

Keywords: Azadirachta indica; Bisphenol; Embryos; Neuroinflammation; Oxidative stress; Zebrafish.

MeSH terms

  • Animals
  • Antioxidants* / metabolism
  • Benzhydryl Compounds / metabolism
  • Benzhydryl Compounds / toxicity
  • Humans
  • Larva
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Zebrafish* / metabolism

Substances

  • Antioxidants
  • Reactive Oxygen Species
  • bisphenol A
  • epoxyazadiradione
  • Benzhydryl Compounds