Synergistic effects of auraptene and 17-β estradiol on traumatic brain injury treatment: oxidant/antioxidant status, inflammatory cytokines and pathology

Int J Neurosci. 2024 Dec;134(12):1477-1489. doi: 10.1080/00207454.2023.2269478. Epub 2023 Oct 19.

Abstract

Objective: Despite significant advances that have been made in the treatment of traumatic brain injury (TBI), it remains a global health issue. This study aimed to investigate the synergistic effects of 17-β estradiol (E2) and auraptene (AUR) on TBI treatment.

Methods: In total, 70 adult male Wistar rats were divided randomly into ten main groups: Sham, TBI, TBI + DMSO, TBI + AUR (4 mg/kg), TBI + AUR (8 mg/kg), TBI + AUR (25 mg/kg), TBI + E2 group, TBI + AUR (4 mg/kg) + E2 group, TBI + AUR (8 mg/kg) + E2 group and TBI + AUR (25 mg/kg) + E2 group. Diffuse TBI was caused by the Marmarou process in male rats. The brain's tissues were harvested to check the parameters of oxidative stress and levels of inflammatory cytokine.

Results: The finding revealed that TBI induced a significant increase in brain edema, pro-inflammatory cytokines and oxidant levels [MDA and NO], and also a decrease in the brain's antioxidant biomarkers [GPx, SOD]. We also found that E2 and AUR (25 mg/kg) significantly preserved the levels of these biomarkers. The combination of AUR concentrations and E2 showed that this treatment efficiently preserved the levels of these biomarkers. Furthermore, the combination of E2 and AUR (25 mg/kg) c could cause the most effective synergistic interaction.

Conclusion: AUR could act synergistically with E2 to treat brain injury complications.

Keywords: 17-β estradiol; TBI; auraptene; oxidative stress.

MeSH terms

  • Animals
  • Antioxidants* / administration & dosage
  • Antioxidants* / pharmacology
  • Brain Edema / drug therapy
  • Brain Edema / etiology
  • Brain Edema / metabolism
  • Brain Injuries, Traumatic* / drug therapy
  • Brain Injuries, Traumatic* / metabolism
  • Coumarins* / administration & dosage
  • Coumarins* / pharmacology
  • Cytokines* / metabolism
  • Drug Synergism*
  • Estradiol* / administration & dosage
  • Estradiol* / pharmacology
  • Male
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress* / drug effects
  • Rats
  • Rats, Wistar*

Substances

  • Estradiol
  • Cytokines
  • aurapten
  • Antioxidants
  • Coumarins
  • Neuroprotective Agents