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Makale Tam Makale Uluslararası 2020 Açık erişimli

Neuroprotective effect of chrysin on isoniazid-induced neurotoxicity via suppression of oxidative stress, inflammation and apoptosis in rats

Hamit Celik, Sefa Küçükler, Selim Çomaklı, Cüneyt Çağlayan, Selçuk Özdemir, Ahmet Yardim, Muhammet Karaman, Fatih Mehmet Kandemir

NeuroToxicology Cilt 81 · ss. 197–208 · 01.12.2020
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Özet

Isoniazid (INH) is among the most important anti-tuberculosis agents widely prescribed. However, its clinical use is restricted due to its severe side effects associated with neurotoxicity. The aim of the present study was to investigate the neuroprotective effects of chrysin (CR), a natural antioxidant, against INH-induced neurotoxicity in rats. The rats were treated orally with INH (400 mg/kg body weight) alone or with CR (25 and 50 mg/kg body weight) for 7 consecutive days. INH administration significantly increased brain lipid peroxidation and resulted in a significant decrease in antioxidant biomarkers including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH). INH treatment also increased levels of nuclear factor kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha), glial fibrillary acidic protein (GFAP) and activities of p38 alpha mitogen-activated protein kinase (p38 alpha MAPK) while decreasing levels of neural cell adhesion molecule (NCAM). Double immunofluorescence expressions of c-Jun N-terminal kinase (JNK) and Bcl-2 associated X protein (Bax) in brain tissues were increased after INH administration. Furthermore, INH increased mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier subunit (Gclm), glutamate cysteine ligase catalytic subunit (Gclc), NF-kappa B, TNF-alpha, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and GFAP in rat brain tissues. Co-treatment with CR increased anti-oxidant capacity as well as regulated inflammation and apoptosis in brain. Additionally, molecular docking results showed that CR had the potential to interact with the active sites of TNF-alpha and NF kappa-B. In conclusion, CR improved INH-induced brain oxidative damage, inflammation and apoptosis, possibly through their antioxidant properties.

Anahtar kelimeler

TISSUE oxidative stress EXPRESSION INFLAMMATION toxicity INHIBITION PATHWAY Molecular docking NF-KAPPA-B ACID PHENETHYL ESTER PROTEIN Isoniazid NEUROTOXICITY INDUCED HEPATOTOXICITY Chrysin ethambutol

Sürdürülebilir Kalkınma Amaçları

  • SKA 3: Sağlıklı Bireyler

Atıf için künye

Celik, H., Küçükler, S., Çomaklı, S., Çağlayan, C., Özdemir, S., Yardim, A., Karaman, M., & Kandemir, F. M. (2020). Neuroprotective effect of chrysin on isoniazid-induced neurotoxicity via suppression of oxidative stress, inflammation and apoptosis in rats. NeuroToxicology, 81, 197–208. https://doi.org/10.1016/j.neuro.2020.10.009

BibTeX 
@article{celik2020-251105,
  author = {Celik, Hamit and Küçükler, Sefa and Çomaklı, Selim and Çağlayan, Cüneyt and Özdemir, Selçuk and Yardim, Ahmet and Karaman, Muhammet and Kandemir, Fatih Mehmet},
  title = {Neuroprotective effect of chrysin on isoniazid-induced neurotoxicity via suppression of oxidative stress, inflammation and apoptosis in rats},
  journal = {NeuroToxicology},
  year = {2020},
  volume = {81},
  pages = {197--208},
  issn = {0161-813X},
  doi = {10.1016/j.neuro.2020.10.009},
  url = {https://akademik.atauni.edu.tr/yayinlar/251105-neuroprotective-effect-of-chrysin-on-isoniazid-induced-neurotoxicity-via}
}