title: TVP1022 attenuates cardiac remodeling and kidney dysfunction in experimental volume overload-induced congestive heart failure.
abstract: BACKGROUND
  Despite the availability of many pharmacological and mechanical therapies, the mortality rate among patients with congestive heart failure (CHF) remains high. We tested the hypothesis that TVP1022 (the S-isomer of rasagiline; Azilect), a neuroprotective and cytoprotective molecule, is also cardioprotective in the settings of experimental CHF in rats.
  
  
  RESULTS
  In rats with volume overload-induced CHF, we investigated the therapeutic efficacy of TVP1022 (7.5 mg/kg) on cardiac function, structure, biomarkers, and kidney function. Treatment with TVP1022 for 7 days before CHF induction prevented the increase in left ventricular end-diastolic area and end-systolic area, and the decrease in fractional shortening measured 14 days after CHF induction. Additionally, TVP1022 pretreatment attenuated CHF-induced cardiomyocyte hypertrophy, fibrosis, plasma and ventricular B-type natriuretic peptide levels, and reactive oxygen species expression. Further, in CHF rats, TVP1022 decreased cytochrome c and caspase 3 expression, thereby contributing to the cardioprotective efficacy of the drug. TVP1022 also enhanced the urinary Na(+) excretion and improved the glomerular filtration rate. Similar cardioprotective effects were obtained when TVP1022 was given to rats after CHF induction.
  
  
  CONCLUSIONS
  TVP1022 attenuated the adverse functional, structural, and molecular alterations in CHF, rendering this drug a promising candidate for improving cardiac and renal function in this disease state.
authors.affiliation: Department of Physiology, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Zaid A
authors.initials: ZA
authors.lastname: Abassi
authors.forename: Yaron D
authors.initials: YD
authors.lastname: Barac
authors.forename: Sawa
authors.initials: S
authors.lastname: Kostin
authors.forename: Ariel
authors.initials: A
authors.lastname: Roguin
authors.forename: Elena
authors.initials: E
authors.lastname: Ovcharenko
authors.forename: Hoda
authors.initials: H
authors.lastname: Awad
authors.forename: Ayelet
authors.initials: A
authors.lastname: Blank
authors.forename: Orit
authors.initials: O
authors.lastname: Bar-Am
authors.forename: Tamar
authors.initials: T
authors.lastname: Amit
authors.forename: Jutta
authors.initials: J
authors.lastname: Schaper
authors.forename: Moussa
authors.initials: M
authors.lastname: Youdim
authors.forename: Ofer
authors.initials: O
authors.lastname: Binah
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis / Q000517:prevention & control; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006984:Hypertrophy / Q000517:prevention & control; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D007189:Indans; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C031967:rasagiline; D020097:Natriuretic Peptide, Brain; D045304:Cytochromes c; D053148:Caspase 3