Thymoquinone has a neuroprotective effect against inflammation, oxidative stress, and endoplasmic reticulum stress in the brain cortex, medulla, and hippocampus due to doxorubicin

KAYMAK E., AKİN A. T., Ozturk E., KARABULUT D., Kuloglu N., YAKAN B.

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, vol.35, no.11, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 35 Issue: 11
  • Publication Date: 2021
  • Doi Number: 10.1002/jbt.22888
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE
  • Keywords: doxorubicin, endoplasmic reticulum stress, inflammation, neurotoxicity, thymoquinone
  • Yozgat Bozok University Affiliated: Yes


Although doxorubicin (DOX) is used in many cancer treatments, it causes neurotoxicity. In this study, the effect of thymoquinone (THQ), a powerful antioxidant, on DOX-induced neurotoxicity was evaluated. In total, 40 rats were used and 5 groups were formed. Group I: control group (n = 8); Group II: olive oil group (n = 8); Group III: the THQ group (n = 8); THQ 10 mg/kg per day was given intraperitoneally (i.p.) throughout the experiment; group IV: DOX group (n = 8); On Day 7 of the experiment, a single dose of 15 mg/kg intraperitoneally DOX injected; group V: DOX + THQ group (n = 8); Throughout the experiment, 10 mg/kg THQ per day and intraperitoneally 15 mg/kg DOX on Day 7 were injected. Immunohistochemically, tumor necrosis factor-alpha (TNF-alpha), interleukin-17 (IL-17), hypoxia-inducible factor 1 alpha (HIF1-alpha), glucose regulatory protein 78 (GRP78), and the gene inducible by growth arrest and DNA damage 153 (GADD153) proteins were evaluated in the brain cortex, medulla, and hippocampus regions. Total oxidant status (TOS) levels and total antioxidant status (TAS) in the brain tissue were measured. TNF-alpha, IL-17, HIF1-alpha, GRP78, and GADD153 immunoreactivities significantly increased in the DOX group in the study. THQ significantly reduced these values. THQ increased the TAS level significantly and decreased the TOS level significantly compared to the DOX group. THQ may play a role as a neuroprotective agent in DOX-induced neurotoxicity in the cortex, medulla, and hippocampus regions of the brain.