title: Clodronate-superparamagnetic iron oxide-containing liposomes attenuate renal injury in rats with severe acute pancreatitis.
abstract: OBJECTIVE
  It has been shown that macrophages play an important role in the development of severe acute pancreatitis (SAP), and eventually lead to multiple organ failure (MOF). Clodronate-liposome selectively depleted macrophages. This study was to investigate the role of renal macrophage infiltration in acute renal injury in rats with SAP and to evaluate the potential of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) for diagnosis.
  
  
  METHODS
  Superparamagnetic Fe3O4 nanoparticles were prepared by chemical coprecipitation. SPIO-liposomes and SPIO-clodronate-liposomes were prepared by the thin film method. SAP models were prepared by injection of sodium taurocholate into the subcapsular space of rat pancreas. Sprague-Dawley rats were randomly divided into a control group, SAP plus SPIO-liposome (P) group, and SAP plus SPIO-clodronate-containing liposome (T) group. Kidney injury was evaluated by T2-weighted MRI scan. The levels of serum amylase (SAM), blood urea nitrogen (BUN), and serum creatinine (SCr) were measured by an automated enzymatic method. Serum tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA). Pathological changes in the pancreas and kidney were observed using hematoxylin and eosin (H&E) staining, while cell apoptosis was detected with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. In addition, the macrophage markers (CD68) of the renal tissue were detected with immunohistochemistry.
  
  
  RESULTS
  The pathological changes in the pancreas and kidneys of rats in the T group were milder than those in the P group. The MRI signal intensity of the kidneys in the P and T groups was significantly lower than that in the control group. There were significant changes in the two experimental groups (P<0.01). The levels of SAM, Bun, SCr, and TNF-α in rats in the P group were higher than those in the control group (P<0.01) and in the T group (P<0.01). The apoptosis of the kidney in the T group was higher than that in the P group at 2 and 6 h (P<0.01).
  
  
  CONCLUSIONS
  Clodronate-containing liposomes protected against renal injury in SAP rats, and SPIO can be used as a tracer for MRI examination to detect renal injury in SAP rats. SPIO-aided MRI provided an efficient non-invasive way to monitor the migration of macrophages after renal injury in rats with SAP.
authors.affiliation: Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.
authors.forename: Sheng-chun
authors.initials: SC
authors.lastname: Dang
authors.forename: Yan-hua
authors.initials: YH
authors.lastname: Zeng
authors.forename: Ping-jiang
authors.initials: PJ
authors.lastname: Wang
authors.forename: Bao-ding
authors.initials: BD
authors.lastname: Chen
authors.forename: Rong-fang
authors.initials: RF
authors.lastname: Chen
authors.forename: Arun
authors.initials: A
authors.lastname: Kumar Singh
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kumar
authors.forename: Shu
authors.initials: S
authors.lastname: Feng
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Jian-xin
authors.initials: JX
authors.lastname: Zhang
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D000818:Animals; D058948:Cell Tracking / Q000379:methods; D004002:Clodronic Acid / Q000627:therapeutic use*; D003287:Contrast Media; D003911:Dextrans; D008081:Liposomes / Q000737:chemistry; D008264:Macrophages / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles; D010195:Pancreatitis / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D003911:Dextrans; D008081:Liposomes; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10; D004002:Clodronic Acid
keywords: Clodronate disodium; Kidney injury; Macrophage; Pancreatitis