Potential of dehydroepiandrosterone and quercetin to ameliorate copper oxide nanoparticles induced hepatotoxicity in albino wistar rats

J Mol Histol. 2024 Nov 30;56(1):17. doi: 10.1007/s10735-024-10311-4.

Abstract

The current investigation was designed as an experimental endeavor to explore the protective efficacy of dehydroepiandrosterone (DHEA) and quercetin against hepatotoxicity induced by copper oxide (CuO) nanoparticles. Rats were subjected to CuO nanoparticle intoxication through intraperitoneal injection of 150 mg/kg b.w. for three weeks, followed by the administration of the aforementioned antioxidants for an additional three weeks. This study systematically tracked alterations in liver enzymatic activity, antioxidant levels, apoptotic markers, and histopathological changes using the comet assay. CuO nanoparticle-intoxicated rats exhibited a significant increase in serum alanine transaminase aspartate aminotransferase (AST), and bilirubin levels, coupled with a noteworthy reduction in serum albumin. Moreover, there was a marked rise in serum tumor necrosis factor-alpha levels, concomitant with a significant decline in serum hepatocyte growth factor (HGF). Caspase-3 and Bax mRNA levels in the serum showed a substantial increase, while serum Bcl-2 mRNA levels witnessed a significant decrease. Liver tissue levels of malondialdehyde (MDA) and nitric oxide (NOx) experienced a significant elevation, and DNA damage was observed through the comet assay. Histopathological examination of the liver tissue substantiated these aforementioned findings. Administration of the antioxidants DHEA or quercetin, either individually or in combination, mitigated the parameters of hepatotoxicity to varying extents. In summary, the hepatic genotoxicity induced by CuO nanoparticles demonstrated improvement following the administration of either DHEA or quercetin. Additionally, their combined administration exhibited a more potent protective potential.

Keywords: Dehydroepiandrosterone; Genotoxicity; Hepatotoxicity; Nanoparticles; Quercetin.

MeSH terms

  • Animals
  • Antioxidants* / metabolism
  • Apoptosis / drug effects
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Copper*
  • DNA Damage / drug effects
  • Dehydroepiandrosterone* / pharmacology
  • Liver* / drug effects
  • Liver* / metabolism
  • Liver* / pathology
  • Male
  • Metal Nanoparticles / chemistry
  • Nanoparticles / chemistry
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects
  • Quercetin* / administration & dosage
  • Quercetin* / pharmacology
  • Rats
  • Rats, Wistar*

Substances

  • Quercetin
  • Copper
  • Dehydroepiandrosterone
  • Antioxidants
  • cuprous oxide
  • Nitric Oxide
  • cupric oxide