title: Protection against ischemia/reperfusion‑induced renal injury by co‑treatment with erythropoietin and sodium selenite.
abstract: Ischemia/reperfusion injury (IRI) has lzong been an area of concern and focus of investigations. Erythropoietin (EPO) exhibits multiple protective effects, and selenium is an antioxidant trace element in the body, however, there have been no reports concerning the effects of EPO combined with sodium selenite on IRI. In the present study, a mouse model of renal IRI (RIRI) was pre‑treated with EPO and sodium selenite to determine the most appropriate combination ratio of the two for further investigation. The results revealed that EPO and sodium selenite had synergistic protective effects in RIRI. EPO was identified as the predominant treatment component, with sodium selenite serving as an adjuvant, and combination treatment was markedly more effective, compared with treatment with either drug alone. The optimal ratio of treatment was 10:1 (10 IU EPO: 1 µg sodium selenite). The results indicated that RIRI markedly induced renal injury, as evidenced by elevated levels of blood urea nitrogen (BUN), as well as higher pathological scores, based on hematoxylin and eosin staining. Pre‑treatment with EPO and sodium selenite significantly decreased serum expression levels of BUN and malonaldehyde, and increased the expression levels of superoxide dismutase, glutathione peroxidase and nitric oxide (NO), compared with the model group. Furthermore, co‑treatment with EPO and sodium selenite upregulated the protein expression levels of phosphatidylinositol‑3 kinase (PI3K) in renal tissue samples. Together, the results suggested that co‑administration of EPO and sodium selenite effectively ameliorates IRI‑induced renal injury by reducing oxidative stress and activating the PI3K/NO signaling pathway.
authors.affiliation: Department of Clinical Medicine, College of Clinical Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Clinical Medicine, College of Clinical Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Clinical Medicine, College of Clinical Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Pharmacology, College of Basic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Clinical Medicine, College of Clinical Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, College of Basic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pathology, College of Basic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, College of Basic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ji
authors.affiliation: Department of Pharmacology, College of Basic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, College of Basic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000517:prevention & control*; D018038:Sodium Selenite / Q000008:administration & dosage / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D020011:Protective Agents; D004921:Erythropoietin; D009569:Nitric Oxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D058539:Phosphatidylinositol 3-Kinase; D018038:Sodium Selenite