title: Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy.
abstract: BACKGROUND
  Curcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300. A novel water soluble curcumin derivative (NCD) has been developed to overcome low invivo bioavailability of curcumin. We evaluated the effect of the NCD on signaling mechanisms involved in cardiomyocyte hypertrophy and studied whether its action is mediated via inducible HO-1.
  
  
  METHODS
  Rats were divided into controls, controls receiving NCD, diabetic, diabetic receiving NCD, diabetic receiving pure curcumin, diabetic receiving HO inhibitor, zinc protoporphyrin IX (ZnPP IX) and diabetic receiving NCD and ZnPP IX. NCD and curcumin were given orally. After 45 days, cardiac physiologic parameters, plasma glucose, insulin, glycated hemoglobin (GHb), HO-1 gene expression and HO activity in pancreas and cardiac tissues were assessed. Gene expression of p300, atrial natriuretic peptide (ANP) and myocyte enhancer factor 2 (MEF2A and MEF2C) were studied.
  
  
  RESULTS
  NCD and curcumin decreased plasma glucose, GHb and increased insulin levels significantly in diabetic rats. This action may be partially mediated by induction of HO-1 gene. HO-1 gene expression and HO activity were significantly increased in diabetic heart and pancreas. Diabetes upregulated the expression of ANP, MEF2A, MEF2C and p300. NCD and curcumin prevented diabetes-induced upregulation of these parameters and improved left ventricular function. The effect of the NCD was better than the same dose of curcumin.
authors.affiliation: Unit of Biochemistry and Molecular Biology, Medical Biochemistry Department, Faculty of Medicine, Cairo University, Kasr El Aini, Cairo, Egypt. talaatabdaziz@yahoo.co.uk.
authors.forename: Mohamed Talaat Abdel
authors.initials: MT
authors.lastname: Aziz
authors.forename: Ibrahim Naguib
authors.initials: IN
authors.lastname: El Ibrashy
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
authors.forename: Ameen Mahmoud
authors.initials: AM
authors.lastname: Rezq
authors.forename: Mohamed Abdel Aziz
authors.initials: MA
authors.lastname: Wassef
authors.forename: Hanan Hassan
authors.initials: HH
authors.lastname: Fouad
authors.forename: Hanan Hosni
authors.initials: HH
authors.lastname: Ahmed
authors.forename: Dina A
authors.initials: DA
authors.lastname: Sabry
authors.forename: Heba Mohamed
authors.initials: HM
authors.lastname: Shawky
authors.forename: Rania Elsayed
authors.initials: RE
authors.lastname: Hussein