title: Hydrogen-Rich Saline Attenuates Acute Kidney Injury After Liver Transplantation via Activating p53-Mediated Autophagy.
abstract: BACKGROUND
  Acute kidney injury (AKI) impacts the survival of liver transplant recipients severely. To date, the related mechanism and effective therapy have not been rigorously explored. The present study aimed to explore the role of p53-mediated autophagy in the protective effect of hydrogen-rich saline (HRS) on AKI after orthotropic liver transplantation (OLT).
  
  
  METHODS
  Adult male Sprague-Dawley rats were randomly allocated into four groups: sham, OLT, OLT with HRS (6 ml/kg) pretreatment (HS), OLT with HRS and chloroquine pretreatment (60 mg/kg) group (CQ). All the samples were collected 6 hours after reperfusion. The renal function and oxidative stress level were measured by biochemical and histopathologic examinations. The formation of autophagosome was observed by transmission electron microscopy. The apoptotic rate was determined by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling analysis. The expression of caspase-3, cytochrome c, p53, damage-regulated autophagy modulator, Becline-1, microtubule-associated protein light 3-II, p62, lysosome-associated membrane protein-2, and the phosphorylation of p53 were assayed by western blot assay.
  
  
  RESULTS
  Compared with the OLT group, HRS dramatically attenuated the histopathologic damage, restored the renal function, and decreased the oxidative stress level. Simultaneously, HRS significantly ameliorated apoptosis by decreasing the apoptotic rate and inhibiting the expression of caspase-3 and cytochrome c in rats subjected to OLT. The expression of Becline-1 and microtubule-associated protein light 3-II were upregulated with the inhibition of p62 and lysosome-associated membrane protein-2. The inhibition of autophagy by chloroquine counteracted the renoprotective effects of HRS.
  
  
  CONCLUSIONS
  HRS is able to protect against AKI after liver transplantation partly by reducing apoptosis, which is possibly involved in the modulation of p53-mediated autophagy.
authors.affiliation: 1 Department of Anesthesiology, Tianjin First Center Hospital, Tianjin, China. 2 Department of Pathology and Pathophysiology, Tianjin Medical University, Tianjin, China. 3 Department of Hepatobiliary Surgery, Tianjin First Center Hospital, Tianjin, China.
authors.forename: Hongyin
authors.initials: H
authors.lastname: Du
authors.forename: Mingwei
authors.initials: M
authors.lastname: Sheng
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Yamin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dongjing
authors.initials: D
authors.lastname: Shi
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Weng
authors.forename: Rubin
authors.initials: R
authors.lastname: Xu
authors.forename: Wenli
authors.initials: W
authors.lastname: Yu
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D006801:Humans; D006859:Hydrogen / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D016031:Liver Transplantation / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D012965:Sodium Chloride / Q000008:administration & dosage*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D016159:Tumor Suppressor Protein p53; D012965:Sodium Chloride; D006859:Hydrogen