title: Targeting tumor necrosis factor alpha (TNF-α) in diabetic rats could approve avenues for an efficient strategy for diabetic therapy.
abstract: BACKGROUND
  Several studies held belief that downregulation of TNF-α may be effective for preventing diabetes and it's complications. However, it is not known whether TNF-α downregulation in long-term can generate any biological adverse.
  
  
  OBJECTIVE
  The aim of the present study was to clarify what the impact is for such treatment with specific antibody for TNF-α on the other biological activities after 4weeks.
  
  
  METHODS
  Using western blot, IHC, Elisa, biochemical assays and scanning electron microscope.
  
  
  RESULTS
  Results show that TNF-α, FOXO-1, IL-6 and MPO, when expressed in diabetic rats, collectively induce dramatic changes in diabetic rats. Since, TNF-α is involved in activation of transcription factor FOXO1 along with oxidative stress mediated by neutrophils. On one hand, IL-6 mediates neutrophils activation leading to an augmentation in stress mediators. And FOXO1 is activated in order to eliminate these oxidative mediators, on the other hand. Data show also that the prominent defect in mucosal IgA and IL-2 secretions may be the leading reasons for digestive atrophy. Finally, Akt-1 inhibits the cleavage of caspase 3, so, it could prevent the incidence of apoptosis.
  
  
  CONCLUSIONS
  Findings of this study reveal how TNF-α can be mechanistically coupled to greater diabetic complications potential.
authors.affiliation: Zoology Department, Division of Physiology, Damanhour University, Egypt. k.kamel2002@yahoo.com
authors.forename: Karolin K
authors.initials: KK
authors.lastname: Abdul-Aziz
authors.forename: Muobarak J
authors.initials: MJ
authors.lastname: Tuorkey
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019902:Chondrocytes / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000187:drug effects*; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D018384:Oxidative Stress; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects*; D015854:Up-Regulation; D000071161:Forkhead Box Protein O1
chemical_list: D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1