ORIGINAL ARTICLE
Year : 2022  |  Volume : 21  |  Issue : 1  |  Page : 9-16

Effect of inositol on ciprofloxacin-induced depression in rats through upregulation of Keap1-Nrf2 system


1 Department of Pharmacology, National Research Centre, Cairo, Egypt
2 Department of Research on Children with Special Needs, National Research Centre, Cairo, Egypt
3 Department of Medical Physiology, National Research Centre, Cairo, Egypt
4 Department of Pathology, National Research Centre, Cairo, Egypt

Correspondence Address:
Abeer Salama
Department of Pharmacology, National Research Centre, 33 El Buhouth Street (Former El-Tahrir Street), Dokki, Cairo 12622
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/epj.epj_53_21

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Background Kelch-like erythroid cell-derived protein 1 (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2) are transcription factors that can protect against oxidative stress and inflammation. Its deficiency has a contributory role in depression. Inositol is a nutritional supplement that is linked to various neurotransmitter receptors, such as serotonin. In the current study, we aimed to investigate the influence of inositol on ciprofloxacin (CPX)-induced depression through the upregulation of Keap1/Nrf2 system. Materials and methods Animals were divided into four groups as follows: group I: the normal control group that received saline. Group II (depressed group): rats treated daily with CPX (50 mg/kg body weight) for 14 days. Groups III and IV: rats received daily inositol (0.625 and 1.25 mg/kg body weight) for 14 days concurrently with daily dose of CPX. Forced swimming, oxidative biomarkers such as nitric oxide, malondialdehyde, and glutathione-s-transferase, and Keap1-Nrf2 and serotonin brain contents were assessed. Results and conclusion CPX-induced oxidative stress, reduced swimming time, and serotonin (5-HT) brain contents and showed severe neural injury in the form of spongiosis, focal gliosis around the degenerating neurons, and injured neurons revealed differences in sizes, vacuolization, shrinking, apoptosis, and lysis. An elevation of swimming time, brain glutathione-s-transferase, serotonin contents with a decrease of nitric oxide and malondialdehyde, and ameliorated histopathological alterations were observed in the inositol-administered group with respect to the CPX group. In conclusion, inositol alleviated neurological toxicity and has antidepressant activity through the downregulation of oxidative stress pathway and upregulation of 5-HT level and Keap1/Nrf2 system.


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