Diphenyl diselenide is as effective as Ebselen in a juvenile rat model of cisplatin-induced nephrotoxicity |
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| Institution: | 1. King’s College London, Department of Nutritional Sciences, School of Life Course Sciences, Metal Metabolism Group, London, UK;2. Kings College London, Centre for Developmental Neurobiology, London, UK;1. Univ Lyon, Univ Jean Monnet, INSERM, U 1059 SainBioSE, F-42023 Saint-Etienne, France;2. University Hospital Saint-Etienne, Department of Gynecology and Obstetrics, F-42055 Saint-Etienne, France;3. Mines Saint-Etienne, Univ Lyon, Univ Jean Monnet, INSERM, U 1059 Sainbiose, Centre CIS, F-42023 Saint-Etienne, France;1. Professor of Medicine and Epidemiology & Community Medicine, University of Ottawa Senior Scientist, Ottawa Hospital Research Institute Scientist, Institute for Clinical Evaluative Sciences, Ottawa, Canada;2. Department of Medicine, University of Ottawa, Ottawa, Canada;3. Department of Pathology & Lab. Medicine, University of Ottawa Clinical Biochemist - Division of Biochemistry, The Ottawa Hospital, Ottawa, Canada;1. Key Laboratory for Special Functional Materials in Jilin Provincial Universities, Jilin Institute of Chemical Technology, Jilin 132022, China;2. Digestive Center, Jilin City People’s Hospital, Jilin 132001, China;3. School of Sciences, Jilin Institute of Chemical Technology, Jilin 132022, China;4. Department of General Surgery, The Second People’s Hospital of Panyu District, Guangzhou 511400, China;1. Medical Physiology Department, Faculty of Medicine, Minia University, Minia, 61111, Egypt;2. Histology and Cell Biology Department, Minia University, Faculty of Medicine, Minia, 61111, Egypt |
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| Abstract: | BackgroundCisplatin (CIS) is widely used in the chemotreatment of pediatric tumors. However, the CIS use is limited because of its high incidence of toxicity, mainly nephrotoxicity. Although there are many studies about CIS-related nephrotoxicity in animal models, only a few studies focus on juvenile animals. Because redox disturbances have been associated with kidney damage induced by CIS, this study aimed to compare the effectiveness of Ebselen and diphenyl diselenide (PhSe)2 against nephrotoxicity induced by CIS in juvenile rats.MethodsJuvenile Wistar rats were randomly divided into six groups: rats from groups I to III received an intraperitoneal (i.p.) injection with saline solution. The other groups received CIS (i.p., 6 mg/kg) on the first day. One hour before CIS injection and on the next four days, animals of groups III and V were intragastrically treated with Ebselen (11 mg/kg) whereas those from groups IV and VI received (PhSe)2 (12 mg/kg). After 24 h of the last treatment, blood and kidney were collected, and the parameters of renal function and oxidative stress were determined.ResultsKidney damage induced by CIS was confirmed by the increase of creatinine, urea and uric acid levels in the blood of juvenile rats. The renal oxidative disturbance was characterized by an increase in the levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl, and nitrogen oxides (Nox), as well as the decrease in non-protein thiol content (NPSH), glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD) activities. CIS inhibited the activities of δ-aminolevulinic acid dehydratase (δ-ALA-D) and Na+, K+-ATPase and down-regulated the Nrf2/Keap-1/HO-1 pathway in the kidney of juvenile rats.ConclusionBoth Ebselen and (PhSe)2 modulated back to the normal levels all parameters altered by the CIS administration in the kidney of juvenile rats. Thus, this study shows that (PhSe)2 was as effective as Ebselen in protecting the kidney against oxidative damage caused by CIS in rats. |
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| Keywords: | Cisplatin Toxicity Juvenile Organoselenium Nrf2/Keap-1/HO-1 pathway |
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