title: Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat.
abstract: Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. Naringin, a natural flavonoid, plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the involvement of ROS overproduction and inflammation in cisplatin-induced nephrotoxicity in aged rats, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after treatment with naringin (20, 50 or 100 mg/kg body weight). Cisplatin resulted in an increase of renal markers, lipid peroxidation, protein and DNA oxidation, and ROS formation. Renal tumor necrosis factor-α (TNF-α) and nitrite levels were also elevated. Expressions of nuclear factor-kappa B (NF-κB), inductible nitric oxide synthase (iNOS), caspase-3 and p53 were up-regulated in renal tissues of Cis-treated rats compared with the normal control group. Histopathological changes were also observed in cisplatin group. Adminstration of naringin at different doses (25, 50 and 100 mg/kg) was able to protect against the deterioration in kidney function, abrogate the decline in antioxidant enzyme activities and suppressed the increase in TBARS, nitrite and TNF-α concentrations. Moreover, naringin inhibited NF-κB and iNOS pathways, caspase-3 and p53 activation and improved the histological changes induced by cisplatin. In conclusion, our studies suggest that oxidative stress and inflammation might play important roles in the development of cisplatin-induced nephrotoxicity and naringin might become an effective therapeutic strategy for this disease.
authors.affiliation: Laboratory of Toxicology 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 and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP1171, 3000, Sfax, Tunisia.
authors.forename: Baktha
authors.initials: B
authors.lastname: Aouey
authors.affiliation: Laboratory of Biochemistry, Molecular Mechanisms and Diseases Research Unit, UR12ES08, Faculty of Medicine, University of Monastir, BP5019, 5000, Monsatir, Tunisia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Aroui
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 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: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D044950:Flavanones / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000032:analysis / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D044950:Flavanones; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C005274:naringin; D002945:Cisplatin
keywords: Aged rat; Chemotherapy; Inflammation; Nephrotoxicity; Oxidative stress