title: Role of inflammatory cytokines and chemoattractants in the rat model of streptozotocin-induced diabetic heart failure.
abstract: OBJECTIVE
  It is not yet clear how oxidative stress, free radicals, inflammatory cytokines and chemoattractants produced in the heart induce chronic heart failure. The myocardial damage caused by chronic diabetes results either from the persistence of inflammatory signaling directly in the heart or from the dysregulation of anti-inflammatory signaling systems. In the rat model of streptozotocin-induced diabetes (STZD) we investigated 1/ the concentration of free radicals (FR), 2/ reduced glutathione (GSH), 3/ lysozomal enzymes, 4/ inflammatory cytokines (tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6)), and monocyte chemoattractant protein-1 (mcp-1) in the myocardium.
  
  
  METHODS
  Diabetes was induced in 12 male Wistar rats by injection of streptozotocin (STZ). The free radical scavenger and cardiac protectant SMe1EC2 (10 mg/kg/d.) was given orally for 5 days and 5 weeks and these animals were compared with the diabetic and non-diabetic controls.
  
  
  RESULTS
  We found reduced heart rate and rate dependent functions of the rat heart, early release of free radicals triggering the release of cytotoxic inflammatory cytokines (like TNF-? and IL-6) and chemoattractants (mcp-1) as an example of this type of pathogens, resulting in the initiation and progression of cardiac pathology. The reduced myocardial contractility after STZD was accompanied with the increased reactive responsiveness of isolated aorta and mesenteric artery to phenylephrine, with increased production of chemoattractive proteins directly in the myocardium, with increased activity of peripheral beta-N-acetyl-glucosaminidase (NAGA), as representative of lysosomal activation processes. The pretreatment of SME1EC2 reduced increase in vascular reactivity, reduced myocardial depression and protected against myocardial toxicity.
  
  
  CONCLUSIONS
  The newly identified and specific cardiac protectant SMe1EC2 could serve as a prospective target in the treatment of increased myocardial cytokine and chemoattractive proteins in diabetic cardiomyopathy.
authors.affiliation: Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic. jan.drimal@savba.sk
authors.forename: Jan
authors.initials: J
authors.lastname: Drimal
authors.forename: Vladimir
authors.initials: V
authors.lastname: Knezl
authors.forename: Jana
authors.initials: J
authors.lastname: Navarova
authors.forename: Jana
authors.initials: J
authors.lastname: Nedelcevova
authors.forename: Ema
authors.initials: E
authors.lastname: Paulovicova
authors.forename: Ruzena
authors.initials: R
authors.lastname: Sotnikova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Snirc
authors.forename: Daniel
authors.initials: D
authors.lastname: Drimal
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002630:Chemotactic Factors / Q000378:metabolism / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D007211:Indoles / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar / Q000378:metabolism; D013311:Streptozocin; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D002630:Chemotactic Factors; D016207:Cytokines; D005609:Free Radicals; D007211:Indoles; D018836:Inflammation Mediators; D015850:Interleukin-6; D011725:Pyridines; C534359:SMe1EC2; D014409:Tumor Necrosis Factor-alpha; D013311:Streptozocin; D000118:Acetylglucosaminidase; D005978:Glutathione