Neuroprotective effect of rutin against colistin-induced oxidative stress, inflammation and apoptosis in rat brain associated with the CREB/BDNF expressions

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Çelik H., Kandemir F. M. , Caglayan C., Özdemir S. , Çomaklı S., Kucukler S. , ...More

Molecular Biology Reports, vol.47, no.3, pp.2023-2034, 2020 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 47 Issue: 3
  • Publication Date: 2020
  • Doi Number: 10.1007/s11033-020-05302-z
  • Title of Journal : Molecular Biology Reports
  • Page Numbers: pp.2023-2034


The purpose of the current study was to examine the neuroprotective effect of rutin against colistin-induced neurotoxicity in rats. Thirty-five male Sprague Dawley rats were randomly divided into 5 groups. The control group (orally received physiological saline), the rutin group (orally administered 100 mg/kg body weight), the colistin group (i.p. administered 15 mg/kg body weight), the Col + Rut 50 group (i.p. administered 15 mg/kg body weight of colistin, and orally received 50 mg/kg body weight of rutin), the Col + Rut 100 group (i.p. administered 15 mg/kg body weight of colistin, and orally received 100 mg/kg body weight of rutin). Administration of colistin increased levels of glial fibrillary acidic protein and brain-derived neurotrophic factor and acetylcholinesterase and butyrylcholinesterase activities while decreasing level of cyclic AMP response element binding protein and extracellular signal regulated kinases 1 and 2 (ERK1/2) expressions. Colistin increased oxidative impairments as evidenced by a decrease in level of nuclear factor erythroid 2-related factor 2 (Nrf-2), glutathione, superoxide dismutase, glutathione peroxidase and catalase activities, and increased malondialdehyde content. Colistin also increased the levels of the apoptotic and inflammatoric parameters such as cysteine aspartate specific protease-3 (caspase-3), p53, B-cell lymphoma-2 (Bcl-2), nuclear factor kappa B (NF-kappa B), Bcl-2 associated X protein (Bax), tumor necrosis factor-alpha (TNF-alpha) and neuronal nitric oxide synthase (nNOS). Rutin treatment restored the brain function by attenuating colistin-induced oxidative stress, apoptosis, inflammation, histopathological and immunohistochemical alteration suggesting that rutin supplementation mitigated colistin-induced neurotoxicity in male rats.