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

• Published in: Molecular biology reports 2020-03, Vol.47 (3), p.2023-2034
• Main Authors: Çelik, Hamit, Kandemir, Fatih Mehmet, Caglayan, Cuneyt, Özdemir, Selçuk, Çomaklı, Selim, Kucukler, Sefa, Yardım, Ahmet
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; AMP; Animal Anatomy; Animal Biochemistry; Animals; Apoptosis; Apoptosis - drug effects; Bax protein; Bcl-2 protein; Biomarkers; Biomedical and Life Sciences; Body weight; Brain - metabolism; Brain - pathology; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Caspase-3; Catalase; Colistin; Colistin - adverse effects; Colistin - pharmacology; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; Extracellular signal-regulated kinase; GA-binding protein; Glial fibrillary acidic protein; Glutathione peroxidase; Histology; Immunohistochemistry; Inflammation - etiology; Inflammation - metabolism; Inflammation - pathology; Life Sciences; Lymphocytes B; Malondialdehyde; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Morphology; Neuronal-glial interactions; Neuroprotection; Neuroprotective Agents - pharmacology; Neurotoxicity; NF-κB protein; Nitric-oxide synthase; Oral administration; Original Article; Oxidative stress; Oxidative Stress - drug effects; Proteins; Rats; Rutin - pharmacology; Superoxide dismutase; Tumor necrosis factor-TNF
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-020-05302-z

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-κB), Bcl-2 associated X protein (Bax), tumor necrosis factor-α (TNF-α) 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.