title: Novel resveratrol analogues attenuate renal ischemic injury in rats.
abstract: BACKGROUND
  Renal ischemia-reperfusion (I/R) is a severe clinical complication with no specific treatment. Resveratrol has been shown as a promising experimental agent in renal I/R due to its effect on cellular energy metabolism, oxidative stress, and inflammation. Recently, we identified two biologically active resveratrol analogues (RSVAs), RSVA405 and RSVA314. We hypothesized that both RSAVs would attenuate I/R-induced renal injury.
  
  
  METHODS
  Adult male rats were subjected to renal I/R through bilateral renal pedicle clamping for 60 min, followed by reperfusion. RSVA405 (3 mg/kg Body Weight), RSVA314 (3 mg/kg Body Weight), or vehicle (10% dimethyl sulfoxide and 33% Solutol in phosphate buffered saline) were administered by intraperitoneal injection 1 h before ischemia. Blood and renal tissues were collected 24 h after I/R for evaluation.
  
  
  RESULTS
  Administration of RSVA405 and RSVA314 significantly reduced the serum levels of renal dysfunction and injury markers, including creatinine, blood urea nitrogen, aspartate aminotransferase, and lactate dehydrogenase, compared with vehicle. The protective effect of RSVA405 and RSVA314 was also reflected on histologic evaluation. Both RSVAs reduced the number of apoptotic cells by more than 60% as determined by transferase dUTP nick end labeling assay, compared with vehicle. The renal adenosine triphosphate levels of the vehicle group was decreased to 52.4% of control, whereas those of the RSVA405 and RSVA314 groups were restored to 72.3% and 79.6% of control, respectively. Both RSVAs significantly reduced the protein expression of inducible nitric oxide synthase and nitrotyrosine and the messenger RNA levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β.
  
  
  CONCLUSIONS
  RSVA405 and RSVA314 attenuate I/R-induced renal injury through the modulation of energy metabolism, oxidative stress, and inflammation.
authors.affiliation: Elmezzi Graduate School of Molecular Medicine, Manhasset, New York; Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York; Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Adam
authors.initials: A
authors.lastname: Khader
authors.affiliation: Elmezzi Graduate School of Molecular Medicine, Manhasset, New York; Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York; Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Weng-Lang
authors.initials: WL
authors.lastname: Yang
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York.
authors.forename: Michael
authors.initials: M
authors.lastname: Kuncewitch
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York; Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Prince
authors.affiliation: Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Philippe
authors.initials: P
authors.lastname: Marambaud
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Nicastro
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York.
authors.forename: Gene F
authors.initials: GF
authors.lastname: Coppa
authors.affiliation: Elmezzi Graduate School of Molecular Medicine, Manhasset, New York; Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York; Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, New York. Electronic address: pwang@nshs.edu.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000517:prevention & control*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000627:Aminophenols / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006835:Hydrazones / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry*
chemical_list: D000627:Aminophenols; D006835:Hydrazones; C570842:RSVA314; C570843:RSVA405; D013267:Stilbenes; D000255:Adenosine Triphosphate; D000077185:Resveratrol
keywords: Energy metabolism; Inflammation; Oxidative stress; Renal ischemia–reperfusion; Resveratrol analogues