title: Vitamin D3 pretreatment alleviates renal oxidative stress in lipopolysaccharide-induced acute kidney injury.
abstract: Increasing evidence demonstrates that reactive oxygen species plays important roles in sepsis-induced acute kidney injury. This study investigated the effects of VitD3 pretreatment on renal oxidative stress in sepsis-induced acute kidney injury. Mice were intraperitoneally injected with lipopolysaccharide (LPS, 2.0mg/kg) to establish an animal model of sepsis-induced acute kidney injury. In VitD3+LPS group, mice were orally pretreated with three doses of VitD3 (25 μg/kg) at 1, 24 and 48 h before LPS injection. As expected, oral pretreatment with three daily recommended doses of VitD3 markedly elevated serum 25(OH)D concentration and efficiently activated renal VDR signaling. Interestingly, LPS-induced renal GSH depletion and lipid peroxidation were markedly alleviated in VitD3-pretreated mice. LPS-induced serum and renal nitric oxide (NO) production was obviously suppressed by VitD3 pretreatment. In addition, LPS-induced renal protein nitration, as determined by 3-nitrotyrosine residue, was obviously attenuated by VitD3 pretreatment. Further analysis showed that LPS-induced up-regulation of renal inducible nitric oxide synthase (inos) was repressed in VitD3-pretreated mice. LPS-induced up-regulation of renal p47phox and gp91phox, two NADPH oxidase subunits, were normalized by VitD3 pretreatment. In addition, LPS-induced down-regulation of renal superoxide dismutase (sod) 1 and sod2, two antioxidant enzyme genes, was reversed in VitD3-pretreated mice. Finally, LPS-induced tubular epithelial cell apoptosis, as determined by TUNEL, was alleviated by VitD3 pretreatment. Taken together, these results suggest that VitD3 pretreatment alleviates LPS-induced renal oxidative stress through regulating oxidant and antioxidant enzyme genes.
authors.affiliation: The Second Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China; Department of Histology and Embryology, Anhui Medical University, Hefei, China.
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: The Second Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Zhu-Xia
authors.initials: ZX
authors.lastname: Tan
authors.affiliation: The Second Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Xie
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: School of Life Science, Anhui Medical University, Hefei, China.
authors.forename: Mi-Zhen
authors.initials: MZ
authors.lastname: Xia
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China. Electronic address: xudex@126.com.
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
authors.affiliation: The Second Affiliated Hospital, Anhui Medical University, Hefei, China. Electronic address: yudx_urology@126.com.
authors.forename: De-Xin
authors.initials: DX
authors.lastname: Yu
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000097:blood; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002762:Cholecalciferol / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000096:biosynthesis; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis; D000072105:Superoxide Dismutase-1; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D000099156:Superoxide Dismutase 2
chemical_list: D015652:25-Hydroxyvitamin D 2; D002762:Cholecalciferol; D005978:Glutathione; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D017382:Reactive Oxygen Species; D018167:Receptors, Calcitriol; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D014443:Tyrosine; D000099156:Superoxide Dismutase 2; C002744:3-nitrotyrosine; C000606291:Sod1 protein, mouse; C488842:Cybb protein, mouse; C060505:neutrophil cytosolic factor 1
keywords: Acute kidney injury; Lipopolysaccharide; Oxidative stress; Vitamin D3