title: Protective role of naringin against cisplatin induced oxidative stress, inflammatory response and apoptosis in rat striatum via suppressing ROS-mediated NF-κB and P53 signaling pathways.
abstract: Cisplatin (Cis) is an effective chemotherapeutic agent successfully used in the treatment of a wide range of malignancies while its usage is limited due to its dose-dependent toxicity. The present study was conducted to investigate the efficacy of naringin, an ubiquitous flavonoid, against Cis-induced striatum injury in Wistar aged rats. Briefly, the experimental procedures were divided in two sets of experiments. In the first, the animals were divided into 4 groups: control, Nar 25mg/kg, Nar 50mg/kg and Nar 100mg/kg. In the second, the animals were divided into 4 groups: Cis (5mg/kg/week for 5 consecutive weeks), Cis+Nar (25mg/kg), Cis+Nar (50mg/kg) and Cis+Nar (100mg/kg). The administration of Cis (5mg/kg/week for 5 consecutive weeks) resulted in a decline in the concentrations of reduced glutathione and ascorbic acid. The activity of membrane bound ATPases and glutathione peroxidase (GPx) were decreased while the activity of catalase (CAT) and superoxide dismutase (SOD) were increased. Further, in striatum tissue, Cis significantly enhance the mRNA gene expression of P53, nuclear factor κB pathway (NFκB) and tumor necrosis factor (TNF-α). Oxidative/nitrosative stress was evident in Cis group by increased malondialdehyde (MDA), protein carbonyls (PCO), reactive oxygen species (ROS) and nitrite concentration (NO). Naringin (25, 50 and 100mg/kg) administration was able to protect against deterioration in striatum tissue, abrogate the change in antioxidant enzyme activities and suppressed the increase in MDA, PCO, NO and TNF-α concentrations. Moreover, Nar inhibited P53, NFkB and TNF-α pathways mediated inflammation and apoptosis, and improved the histological changes induced by Cis. Thus, these findings demonstrated the neuroprotective nature of Nar by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant competence in striatum tissue. These results imply that Nar has perfect effect against Cis-induced striatum injury in aged rats, which should be developed as an effective food and healthcare product for the treatment of brain injury in the future.
authors.affiliation: Laboratory of Toxicology-Microbiology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP1171, 3000 Sfax, Tunisia.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Chtourou
authors.affiliation: Laboratory of Toxicology-Microbiology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP1171, 3000 Sfax, Tunisia.
authors.forename: Bakhta
authors.initials: B
authors.lastname: Aouey
authors.affiliation: Molecular Biology Laboratory, Faculty of Nature and Life Sciences, University of Jijel, PB 98, Ouled Aissa 1800, Jijel, Algeria.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kebieche
authors.affiliation: Laboratory of Toxicology-Microbiology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP1171, 3000 Sfax, Tunisia. Electronic address: fetoui_hamadi@yahoo.fr.
authors.forename: Hamadi
authors.initials: H
authors.lastname: Fetoui
mesh_terms: D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D004660:Encephalitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D004798:Enzymes / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004798:Enzymes; D044950:Flavanones; D016328:NF-kappa B; D009573:Nitrites; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; C005274:naringin; D002945:Cisplatin
keywords: Aged rat; Chemotherapy; Inflammation; Oxidative stress; P53 expression; Striatum