Multixenobiotic resistance mechanism: Organ-specific characteristics in the fish Prochilodus lineatus and its role as a protection against genotoxic agents

Comp Biochem Physiol C Toxicol Pharmacol. 2021 May:243:108996. doi: 10.1016/j.cbpc.2021.108996. Epub 2021 Feb 3.

Abstract

The multixenobiotic resistance mechanism (MXR) can decrease intracellular genotoxic pressure through the efflux of compounds out of the cell. Thus, this work presents a temporal approach to evaluate the MXR activity and the occurrence of genotoxic damage in different organs of the fish Prochilodus lineatus after an intraperitoneal injection of benzo[a]pyrene (B[a]P). Although the liver and brain demonstrated rapid MXR induction (6 h), the occurrence of DNA damage was not prevented. However, these organs presented some return to DNA integrity after MXR activity. The kidney demonstrated the slowest response in the MXR induction (24 h), which may be related to the preferential excretion of B[a]P metabolites by this route. Moreover, the kidney MXR reduction at 96 h may be related to its role in the excretion of metabolites from all other metabolizing organs. The gills did not appear to play an essential role in xenobiotics efflux; however, their participation in biotransformation is exhibited through the occurrence of DNA damage. The integrated response of the organs in the dynamics for the maintenance of the organism integrity could be promoted by the circulation of the xenobiotic through the bloodstream, which corroborates the increase in the DNA damage in the erythrocytes at 6 h. Therefore, the ability to induce MXR was linked to the preservation of DNA integrity in the presence of B[a]P, since MXR acts to avoid the accumulation of xenobiotics inside the cell.

Keywords: Benzo[a]pyrene; DNA damage, comet assay; Rhodamine B; Temporal approach.

MeSH terms

  • Animals
  • Benzo(a)pyrene* / pharmacokinetics
  • Benzo(a)pyrene* / toxicity
  • Biotransformation
  • Brain / drug effects
  • Characiformes / metabolism*
  • DNA / metabolism
  • DNA Damage
  • Gills / drug effects
  • Liver / drug effects
  • Water Pollutants, Chemical* / pharmacokinetics
  • Water Pollutants, Chemical* / toxicity
  • Xenobiotics* / pharmacokinetics
  • Xenobiotics* / toxicity

Substances

  • Water Pollutants, Chemical
  • Xenobiotics
  • Benzo(a)pyrene
  • DNA