title: Nephroprotective Effects of Polydatin against Ischemia/Reperfusion Injury: A Role for the PI3K/Akt Signal Pathway.
abstract: Oxidative stress and inflammation are involved in the pathogenesis in renal ischemia/reperfusion (I/R) injury. It has been demonstrated that polydatin processed the antioxidative, anti-inflammatory, and nephroprotective properties. However, whether it has beneficial effects and the possible mechanisms on renal I/R injury remain unclear. In our present study I/R models were simulated both in vitro and in vivo. Compared with vehicle control, the administration of polydatin significantly improved the renal function, accelerated the mitogenic response and reduced cell apoptosis in renal I/R injury models, strongly suppressed the I/R-induced upregulation of the expression of tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, inducible nitric oxide synthase, prostaglandin E-2, and nitric oxide levels, and dramatically decreased contents of malondialdehyde, but it increased the activity of superoxide dismutase, glutathione transferase, glutathione peroxidase and catalase, and the level of glutathione. Further investigation showed that polydatin upregulated the phosphorylation of Akt in kidneys of I/R injury dose-dependently. However, all beneficial effects of polydatin mentioned above were counteracted when we inhibited PI3K/Akt pathway with its specific inhibitor, wortmannin. Taken together, the present findings provide the first evidence demonstrating that PD exhibited prominent nephroprotective effects against renal I/R injury by antioxidative stress and inflammation through PI3-K/Akt-dependent molecular mechanisms.
authors.affiliation: Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China ; State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Hong-Bao
authors.initials: HB
authors.lastname: Liu
authors.affiliation: Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Qiu-Hong
authors.initials: QH
authors.lastname: Meng
authors.affiliation: Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D005960:Glucosides; D053583:Interleukin-1beta; D020011:Protective Agents; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D010088:Oxidoreductases; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C058229:polydatin